Potassium ion KV1.3 channel inhibitors

Abstract

The invention relates to potassium ion channel inhibitor compounds having improved affinity and selectivity for Kv1.3 ion channel, and enhanced stability. The inhibitor compounds comprise a polypeptide component which is a miniprotein. The invention also relates to therapeutic indications and diagnostic uses of the inhibitor compounds.

Description

[0001]Potassium ion channel inhibitors FIELD OF THE INVENTION The invention relates to potassium ion channelb iintohri compounds having improved affinity and seivleitcyt for Kv1.3 ion channel, and enhanced stability. T inhheibitor compounds comprise a polypeptide compotn wehnich is a miniprotein. The invention also relates to theruatpic indications and diagnostic uses of the intohrib ciompounds. TECHNICAL BACKGROUND Voltage-gated potassium channels (Kvs) are actdiva btye changes in cell membrane potential and are selectively permeable for potassium ions. Kv channels are typically homotetramers with ar caeln iotn pore. The subunits (alpha-subunits) of te thtreamers have six transmembrane domains (S1-S6) providign.g th ee. voltage-gate and selective potassium iotenr f fiul nctions.An associated regulatory subunit, such as the Ktav s buebunit provides other functions such as reigounla otf channelexpression, voltage sensitivity and kinetics ofa psostium current, influenced by integrins and othoelre mcules involved in signal transduction. Kv1.3 channels of the plasma membrane, first dbeesdcri in 1984 in T lymphocytes, are activated by depolarization of T-cells expressing them, lead tiong potassium efflux that acts to restore the regs mtinembrane potential. During T cell activation, C2a+enters the cell through C2+a release activated C2+a (CRAC) channels. The driving force required for the adequate2C+ianflux is assured by the+K channels of T cells which compensate the depoinlagriz effect of the C2a+influx by K+efflux [Panyi G. et al., 200]4. Thus, the K+channels play an important facilitating role in the Ca2+signal required for T cell activation, and theliorc bkade leads to the inhibition of proliferation T of cells invitro and in vivo [Lowinus T. et al., 2020]. There are two types p o tfassium channels that play such facilitatorys rolein T cell activation and proliferation, the membera pnotential dependent voltage gated Kv1.3 chann aenlds, the intracellular calcium concentration dependent cuamlci activated KCa3.1 channels. The expression of.3 Kv a1nd KCa3.1 changes during T cell activation and difnfetiraetion. Initially, T cells up-regulate KCa3.1 unpo activation by an antigen. However, with repeated antigen stimiounla,t they switch to up-regulating Kv1.3. This dirfefence in K+channel expression between acutely activated arnodni ch ally activated T cells highlights the signaifincce of Kv1.3 asa therapeutic target in chronic inflammatory diseesa,s including autoimmune diseases. Autoreactive T cells play a central role in autoimunme diseases (ADs). Kv1.3 and KCa3.1 ion channrels aexpressed differently in T cell subtypes, offeri ang way to selectively modulate T cell responses.ra Ocvteive autoreactive T cells, particularly the so-callefdfe ‘cetor memory T’ (Tem) cells with high Kv1.3 expsrseion, contribute to AD pathogenesis. Tem cell phenotype is obse frovre edxample in multiple sclerosis (MS), type-1 deiatebs mellitus (T1DM) and rheumatoid arthritis (RA [)Cañas, C. A. et al., 202].2 Inhibition of Kv1.3 has proven to be effective in treating ADs in animal models without compromisi tnhge protective immune response provided by othe crel Tls [Chandy, K. G. et al., 2023]. Kv1.3 blockers have been reported to be effectniv aen iimal models of memory T cell mediated delayyepde-t hypersensitivity (DTH), experimental autoimmune e epnhcalomyelitis (EAE), arthritis, autoimmune diabse,te transplantation, allergic dermatitis and psoria ssuigsgesting that Kv1.3 blockers may have the poatel fnotri treatmentof human autoimmune diseases [Fung-Leung, W. a Pl. , e 2t017].Chronic inflammatory immune-mediated diseases p ao gsreowing public health challenge despite advan incesdiagnosis and treatment. Current therapies oftveonlv ine broad immunosuppression with an unfavoraibdle s effect profile, such as upper respiratory infections, npahsaoryngitis, herpes virus infection or even thromembobolism. Therefore, there is a pressing need for more pere imcims unomodulators to effectively manage them w miitnhimal side effects, better patient compliance, and improvesdt- ceoffectiveness. Blockers of Kv1.3 channels have therapeutic poateln atciross various conditions. Kv1.3 channels avroelv inedin the activation and proliferation of various c teylpl es, including tumor cells [Bielanska, J. e,t 2 a0l.09], microglia[Khanna, R. et al., 2001], and neuronal progenit [oWrsang, T. et al., 2010], suggesting potential r iena t ingneuroinflammatory and neurodegenerative disord aesrs w,ell as cancers. They exhibit beneficial metiacb eoflfects such as reducing weight gain, improving insulins siteivnity, and decreasing plasma glucose levelsig inh- hfat diet mice [Xu, J. et al., 2003]. In smooth muscle prolifevraeti disorders, like restenosis post-angioplasty,.3 Kv b1lockers are effective by inhibiting smooth muscle cell proliafetiron and migration [Cheong, A. et al., 2011]. Various toxins may be considered as inhibitorso otaf s psium channels. Kv1.3 inhibition with KTX1 and ShK toxin suppress ceystokine production, inhibits proliferation of Te cmells and ameliorates disease manifestation in animale mlso odf EAE [Norton, R.S. et al., 2004]. For example, Vm24 toxin from V. mexicanus is a potent and moderately selective Kv1.3 chan bnloeclker, which has been shown to effectively reduce the D rTeHsponse, an important finding for development of immunosuppressants for humans [Varga Z. et al.2,] 2.01 However, many toxins affect other related potass ciuhmannels (Kv1.1, Kv1.2, Kv1.6, Kv1.7) of neuronnsd a muscle cells, which can cause adverse effe [Cctasñ.as, C. A e.t al., 2022]. Several attempts have been made in the art tod pero Kvvi1.3 inhibitors. WO 2014 / 116937 discloses Kv1.3 antagonists ando mdesth for using them in therapy. WO 2015 / 013330 discloses Stichodactyla (ShK) tobxains-ed therapeutic peptides for treating ophthalmic conditions. It is suggested that these ShK-basepdtid pees treat dry eye and other inflammatory ophmthical conditions by blocking Kv1.3 channels. WO 2021 / 053194 discloses blockers of the potass cihuamnnel Kv1.3 derived from P aarabuthus transvaalicus scorpion toxin (PaT1). US 20230331827A discloses potassium channel Kvn1h.3ibi itors and their use in medicine, including for treatment of autoimmune conditions. These inhibsit coormprise a fusion protein and a partner domahine,re win the fusion protein comprises a Kv1.3-binding peptid.eg. (e HsTX1, ShK or KTX1) inserted within an antibo vdayriable domain, and wherein the partner domain is for exleam anp antibody variable domain. Clinical utility of bioactive native peptides caen h bindered by poor serum stability resulting inr sth coirculatingplasma half-life. Therefore, good serum stabilisty a i crucial feature affecting the therapeutic vliitaybi of a drug candidate. For example, Dalazatide, a synthetician vtar of ShK toxin derived from the sea anemoneh Sotdicactyla helianthus, has completed phase 1b clinical tr biaulst, its development was apparently halted. Thi1s. K3v inhibitor has shown promise in the treatment of psoriasis byif siciganntly lowering plasma levels of various inflamamtion markers and alleviating the severity of the disease. Spiceaclliyf, in mild-to-moderate plaque psoriasis pattsie rneceiving 60 mcg of Dalazatide, there was a statistically sigcnainft decrease in the average Psoriasis Area Styev Inedriex (PASI) score, indicating its potential efficacy [Tarcha.J,. E et al., 2012, 2017]. Nevertheless, Dalazatiadse a wssociated withmild but dose-limiting side effects such as hyphoes ita and paresthesia, which may have hindere adb it listy todemonstrate clinically significant efficacy. Thiosu cld be due to the inhibition of Kv1.1 and Kv1.2n io channels by Dalazatide and / or its metabolite that readily for umpson exposure to human serum and plasma [Tarc.hJ.a, et E al., 2017]. There is still a need for new Kv1.3 blockers wimthp iroved selectivity over existing ones. Enhancems e innt potency and stability are also desirable. BRIEF DESCRIPTION OF THE INVENTION The invention relates to highly selective Kv1.3a psostium channel inhibitor compounds. 1. Specifically, the invention relates to the fowlliong Kv1.3 potassium channel inhibitor compounds. 1.1 A Kv1.3 potassium channel inhibitor compound, coimsinpgr a Kv1.3 inhibitor polypeptide component, wherein said polypeptide component comprises three diseul bfirdidges and said polypeptide component comprises the follow aimngino acid sequence of formula (1) or a sequenmcepr ciosing at most 1 or 2 or 3 further mutations, preferably aots mt 1 or 2 or 3 conservative replacements: wherein, independently, X1 is any proteinogenic amino acid, or a non-proteinogenic amino acid selected from the group consisting of norleucine (Nle), sarcosine (MeGly), 2,3-diaminoppioronic acid (Dpr), 2,4-diaminobutyric acid (Dbu)r,n oithine (Orn), homo-lysine (hLys), norvaline (Nv,a 2)-aminobutyric acid (Abu), 2-aminoisobutyric ac (iAdib), homo- glutamine (hGln), beta-hydroxynorvalinβe-O ( H-Nva), 3-iodo-tyrosine (3I-Tyr), citrulline, peipcolic acid (Pip), azetidine-2-carboxylic acid (Aze) and a Phe deirvivea;t or a deletion; X2 is any proteinogenic amino acid, or a non-proteinogenic amino acid selected from the group consisting of Nle, sarcosine (MeGly), 2,3-diaminopropionic acDidp (r), 2,4-diaminobutyric acid (Dbu), Orn, homo-lnyesi (hLys), Nva, Abu, Aib, homo-glutamine (hGln), beta-hydroxynolrinvae (β-OH-Nva), 3-iodo-tyrosine (3I-Tyr), citrulline, pipecolic acid (Pip) or azetidine-2-carboxylicd ac (Ai ze) and a Phe derivative; or a deletion; X3 is any proteinogenic amino acid, or a non-proteinogenic amino acid selected from the group consisting of Nle, sarcosine (MeGly), 2,3-diaminopropionic acDidp (r), 2,4-diaminobutyric acid (Dbu), Orn, homo-lnyesi (hLys), Nva, Abu, Aib, homo-glutamine (hGln), beta-hydroxynolrinvae (β-OH-Nva), 3-iodo-tyrosine (3I-Tyr), citrulline, pipecolic acid (Pip), azetidine-2-carxbyolic acid (Aze) and a Phe derivative; or a deletion; X4 is any proteinogenic amino acid, or a non-proteinogenic amino acid selected from the group consisting of Nle, sarcosine (MeGly), 2,3-diaminopropionic acDidp (r), 2,4-diaminobutyric acid (Dbu), Orn, homo-lnyesi (hLys), Nva, Abu, Aib, homo-glutamine (hGln), beta-hydroxynolrinvae (β-OH-Nva), 3-iodo-tyrosine (3I-Tyr), citrulline, pipecolic acid (Pip), azetidine-2-carboxylic ac (Aidze) and a Phe derivative; or a deletion; X5 is any proteinogenic amino acid, or a non-proteinogenic amino acid selected from the group consisting of Nle, sarcosine (MeGly), 2,3-diaminopropionic acDidp (r), 2,4-diaminobutyric acid (Dbu), Orn, homo-lnyesi (hLys), Nva, Abu, Aib, homo-glutamine (hGln), beta-hydroxynolrinvae (β-OH-Nva), 3-iodo-tyrosine (3I-Tyr), citrulline, pipecolic acid (Pip) or azetidine-2-carboxylicd ac (Ai ze) and a Phe derivative; or a deletion; X6 is a hydrophobic amino acid, an acidic aminod a ocri a basic amino acid, preferably selected froaml(V V), Glu(E) and / or Lys(K), respectively, or a non-proteinogenic amino acid selected from the group consisting,3 o-fd 2iaminopropionic acid (Dpr), 2,4- diaminobutyric acid (Dbu), Orn, homo-lysine (hLy Ns)v,a, Abu, Aib and homo-glutamine (hGln), or a deletion; X7 is Pro(P), Lys(K), Glu(E) or Ser(S), or a non-proteinogenic amino acid selected from the group consisting of 2,3-diaminopropionic acid (Dpr), 2,4-diaminobutyr aic id (Dbu), Orn, homo-lysine (hLys), homo-glutame in(hGln), pipecolic acid (Pip) or azetidine-2-carboxylic ac (Aidze) and Aib; or a deletion; or any one of X1to X7is a pyroglutamate (pGlu), provided that said p iGsl Nu-terminal, X9 is Thr(T), Lys(K), or Ser(S), or a non-proteinogenic amino acid selected from the group consisting of beta-hydroxynorvalineβ (-OH-Nva), 2,3-diaminopropionic acid (Dpr), 2,4-diianmobutyric acid (Dbu), Orn, homo- lysine (hLys) and Aib, X10 is Gly(G), His(H) or Ala(A), or a non-proteinogenic amino acid selected from the group consistinga orcfo ssine (MeGly), Abu and Aib; X12 is Pro(P), Gly(G), Lys(K) or Arg(R), or a non-proteinogenic amino acid selected from the group consisting of sarcosine (MeGly), 2,3-diaminopropionic acid (Dp 2r,)4,-diaminobutyric acid (Dbu), Orn, homo-lysineLy (hs), citrulline, pipecolic acid (Pip), azetidine-2-carxbyolic acid (Aze), X13 is Gln(Q), Asp(D), Glu(E), Asn(N), or homo-galumtine (hGln); preferably Gln(Q) or Asp(D) or homlou-tgamine (hGln), X15 is Leu(L), Lys(K) or Val(V), preferably Leu(L), or a non-proteinogenic amino acid selected from the group consisting of Nle, 2,3-diaminopropionic acid (Dpr), 2,4-diaminotybruic acid (Dbu), Orn, homo-lysine (hLys), N,v Aabu, Aib and homo-glutamine (hGln); X16 is Gln(Q), Glu(E) or Lys(K), or a non-proteinogenic amino acid selected from the group consisting of 2,3-diaminopropionic acid (Dpr), 2,4-diaminobuty aric id (Dbu), Orn, homo-lysine (hLys) and homo-gmluitnae(hGln), X17 is Ser(S), Lys(K) or Ala(A), or a non-proteinogenic amino acid selected from the group consisting of Abu, Aib, 2,3-diaminopropionic acid (Dpr), 2,4-diaminobuty aric id (Dbu), Orn, homo-lysine (hLys) and homo-glutamine (hGln); X23 is Met(M) or Nle, X24 is Arg(R) or Thr(T), a non-proteinogenic amino acid selected from the group consistingit orufl cline and beta-hydroxynorvalineβ- ( OH-Nva), X25 is Tyr(Y) or Phe(F), or a non-proteinogenic amino acid selected from the group consisting- oiofd 3o-tyrosine (3I-Tyr) and a Phe derivative; X29 is Met(M) or Nle, X31 is Arg(R), Lys(K) or Gly(G), preferably Arg(R o)r Gly(G), or a non-proteinogenic amino acid selected from the group consisting of citrulline, 2,3-diaminopropionic acid (Dpr), 2,4a-dmiinobutyric acid (Dbu), Orn, homo-lysine (hLys)d an sarcosine (MeGly), X34 is Lys(K) or Arg(R), or a non-proteinogenic amino acid selected from the group consisting of 2,3-diaminopropionic acid (Dpr), 2,4-diaminobuty aric id (Dbu), Orn, homo-lysine (hLys) and citrull;ineX36 is Phe(F), Tyr(Y) or Ser(S), preferably Phe o(Fr) Tyr(Y), more preferably Phe(F), or a non-proteinogenic amino acid selected from the group consistingi obf, A 3-iodo-tyrosine (3I-Tyr) and a Phederivative, preferably a Phe derivative, X37 is Gly(G), Ser(S) or Pro(P), preferably Gly( oGr) Pro(P), or a non-proteinogenic amino acid selected from the group consistinga orcfo ssine (MeGly), pipecolic acid (Pip), and azetidine-2-carboxylic acid (Aze), or a deletion; X38 is Lys(K), Arg(R), or a hydrophobic amino ac iind, particular Lys(K), Arg(R), or Ile(I), preferaybl Arg(R), or a non-proteinogenic amino acid selected from the group consisting of 2,3-diaminopropionic acid (Dpr), 2,4-diaminobutyr aic id (Dbu), Orn, homo-lysine (hLys), citrulline,va N andNle, preferably citrulline; or a deletion; wherein a Phe-derivative is selected from the gr coounpsisting of - 4-fluoro-phenylalanine, - 4-amino-phenylalanine, - 4-nitro-phenylalanine, - 4-methyl-phenylalanine; and wherein optionally any one of said amino acidsn is al apha-methyl amino acid, in particular at mos atm 5ino acids are alpha-methyl amino acids; wherein optionally any one of said amino acidso astit pions from 1 to 10, preferably 1 to 7 and 2124 to is an N- methyl amino acid, in particular at most 5 aminoids ac are N-methyl amino acids; wherein optionally any one, at most 5 amino aceidlesc sted from X1, X2, X3, X4, X5 is / are D amino asc;id or a salt thereof, preferably a pharmaceuticallcye apctable salt thereof,wherein said inhibitor compound is capable of steivlec ly inhibiting a Kv1.3 potassium channel prot.einIn an embodiment, the N-terminus may be a pyrogmluata e (pGlu); i.e. the N-terminus may be a pyrogmluattae (pGlu)in any formula of the invention. In one embodiment, the polypeptide component coisminpgr the amino acid sequence of formula (1) also comprises 3 further mutations. In another embodtim, tehne polypeptide component comprising the amicnido asequence of formula (1) also comprises 2 furthetra mtiouns. In another embodiment, the polypeptidep co nmentcomprising the amino acid sequence of formula l (s1o) c aomprises 1 further mutation. In another emmboednit, thepolypeptide component comprising the amino acidue senqce of formula (1) does not comprise any fur mthuetrations. Preferably, in formula (1) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 X X X X X X X CX X SX X CX X X C K E A GX X X G K CX NX K CX CX X X(1)(as shown in SEQ ID NO: 64), independently, X1 is any proteinogenic amino acid, or a non-prnootegienic amino acid selected from the group consgis otif pyroglutamate (pGlu), Nle, sarcosine (MeGly), 2i,a3m-dinopropionic acid (Dpr), 2,4-diaminobutyric ac (iDdbu), Orn, homo-lysine (hLys), Nv,a Abu, Aib, homo-glutamine (hGln), beta-hydroxynolrinvea (β-OH-Nva), 3-iodo- tyrosine (3I-Tyr), citrulline, pipecolic acid (Pi,p a)zetidine-2-carboxylic acid (Az,e a) Phe derivative; or a deletion; X2 is any proteinogenic amino acid, or a non-prnootegienic amino acid selected from the group consgis otif Nle, sarcosine (MeGly), 2,3-diaminopropionic acDidp (r), 2,4-diaminobutyric acid (Dbu), Orn, homo-lnyesi (hLys), Nva, Abu, Aib, homo-glutamine (hGln), beta-hydroxynolrinvae (β-OH-Nva), 3-iodo-tyrosine (3I-Tyr), citrulline, pipecolic acid (Pip) or azetidine-2-carboxylicd ac (Ai ze) and a Phe derivative; or a deletion; X3 is any proteinogenic amino acid, or a non-prnootegienic amino acid selected from the group consgis otif Nle, sarcosine (MeGly), 2,3-diaminopropionic acDidp (r), 2,4-diaminobutyric acid (Dbu), Orn, homo-lnyesi (hLys), Nva, Abu, Aib, homo-glutamine (hGln), beta-hydroxynolrinvae (β-OH-Nva), 3-iodo-tyrosine (3I-Tyr), citrulline, pipecolic acid (Pip), azetidine-2-carxbyolic acid (Aze) and a Phe derivative; or a deletion; X4 is any proteinogenic amino acid, or a non-prnootegienic amino acid selected from the group consgis otif Nle, sarcosine (MeGly), 2,3-diaminopropionic acDidp (r), 2,4-diaminobutyric acid (Dbu), Orn, homo-lnyesi (hLys), Nva, Abu, Aib, homo-glutamine (hGln), beta-hydroxynolrinvae (β-OH-Nva), 3-iodo-tyrosine (3I-Tyr), citrulline, pipecolic acid (Pip), azetidine-2-carboxylic ac (Aidze) and a Phe derivative; or a deletion; X5 is any proteinogenic amino acid, or a non-prnootegienic amino acid selected from the group consgis otif Nle, sarcosine (MeGly), 2,3-diaminopropionic acDidp (r), 2,4-diaminobutyric acid (Dbu), Orn, homo-lnyesi (hLys), Nva, Abu, Aib, homo-glutamine (hGln), beta-hydroxynolrinvae (β-OH-Nva), 3-iodo-tyrosine (3I-Tyr), citrulline, pipecolic acid (Pip) or azetidine-2-carboxylicd ac (Ai ze) and a Phe derivative; or a deletion; X6 is selected from Val(V), Glu(E) or Lys(K), or n aon-proteinogenic amino acid selected from thep gr coounsisting of 2,3-diaminopropionic acid (Dpr), 2,4-diaminobruicty acid (Dbu), Orn, homo-lysine (hLys), N,v Aabu, Aib and homo-glutamine (hGln); or a deletion;X7 is Pro(P), Lys(K), Glu(E) or Ser(S), or a nono-tperinogenic amino acid selected from the groupi csotins g of2,3-diaminopropionic acid (Dpr), 2,4-diaminobutyr aic id (Dbu), Orn, homo-lysine (hLys), homo-glutame in(hGln), pipecolic acid (Pip) or azetidine-2-carboxylic ac (Aidze) and Aib; or a deletion; X9 is Thr(T), Lys(K), or Ser(S), or a non-proteineongic amino acid selected from the group consis otifng beta-hydroxynorvalineβ (-OH-Nva), 2,3-diaminopropionic acid (Dpr), 2,4-diianmobutyric acid (Dbu), Orn, homo- lysine (hLys) and Aib; X10 is Gly(G), His(H) or Ala(A), or a non-proteineongic amino acid selected from the group consis otifng sarcosine (MeGly), Abu and Aib;X12 is Pro(P), Gly(G), Lys(K) or Arg(R), or a nonro-pteinogenic amino acid selected from the groupsi csotin g ofsarcosine (MeGly), 2,3-diaminopropionic acid (Dp 2r,)4,-diaminobutyric acid (Dbu), Orn, homo-lysineLy (hs), citrulline, pipecolic acid (Pip), azetidine-2-carxbyolic acid (Aze), X13 is Gln(Q) or Asp(D); or homo-glutamine (hGln); X15 is Leu(L) or Nva; X16 is Gln(Q), Glu(E) or Lys(K), or a non-proteineongic amino acid selected from the group consis otifng 2,3-diaminopropionic acid (Dpr), 2,4-diaminobutyr aic id (Dbu), Orn, homo-lysine (hLys), homo-glutame in(hGln), X17 is Ser(S), Lys(K) or Ala(A), or a non-proteineongic amino acid selected from the group consis otifng Aib, Abu, 2,3-diaminopropionic acid (Dpr), 2,4-diaminobutyr aic id (Dbu), Orn, homo-lysine (hLys), homo-glutamine (hGln); X23 is Met(M) or Nle, X24 is Arg(R) or Thr(T), a non-proteinogenic ami ancoid selected from the group consisting of citnruel,li or beta- hydroxynorvalineβ (-OH-Nva), X25 is Tyr(Y) or Phe(F), or a non-proteinogenicn aom ai cid selected from the group consisting of 3o--iotydrosine (3I- Tyr) or a Phe derivative; X29 is Met(M) or Nle,X31 is Arg(R) or Gly(G), or a non-proteinogenic anmoi acid selected from the group consisting of clli ntreu andsarcosine (MeGly), X34 is Lys(K) or Arg(R), or a non-proteinogenic anmoi acid selected from the group consisting of 2,3- diaminopropionic acid (Dpr), 2,4-diaminobutyricd ac (iDbu), Orn, homo-lysine (hLys), citrulline; X36 is Phe(F) or Tyr(Y), more preferably Phe(F), a or non-proteinogenic amino acid selected from trhoeup g consisting of 3-iodo-tyrosine (3I-Tyr a)nd a Phe derivative, preferably a Phe derivative, X37 is Gly(G) or Pro(P), or a non-proteinogenic n aomi acid selected from the group consisting of poipliecc acid sarcosine (MeGly), pipecolic acid (Pip), or azenteid-i2-carboxylic acid (Aze), or a deletion; X38 is Lys(K), Arg(R), or Ile(I), preferably Arg(R,) or citrulline; or a deletion. Preferably, if X36 is Tyr then X37 is different fmro Ser, in particular if X38 is deleted. Preferably, X36 is different from Tyr if X37 is S,e inr particular if X38 is deleted. Preferably, X36 is Phe(F) or Ser(S). Preferably, X37 is Gly(G) or Pro(P). In an embodiment, any one of X1 to X7 is a pyroagmluatte (pGlu), provided that said pGlu is N-term.inal In an embodiment, if at the N-terminus there is, a it Q may be a pyroglutamate (pGlu); i.e. Q maye bpela rced by a pyroglutamate (pGlu) in any formula of the invent.io In a preferred embodiment said Kv1.3 potassiumn cehla in hibitor compound has the following formula.b ()1: (wherein the sequence between R1 and R2 is show SnEQ in ID NO: 63; a preferred variant in SEQ ID NO4: o 6r in any SEQ ID NOs selected from the group consistifn SgE oQ ID NO: 65 to 85), wherein R1 is a moiety covalently linked to the N-termin parle,ferably said moiety comprising a conjugatingie mtyo, a further polypeptide sequence or a moiety comprising borth R;1 o is nothing, R2 is a moiety covalently linked to the C-termin parle,ferably said moiety comprising a conjugatingie mtyo, a further polypeptide sequence or a moiety comprising borth R;2 o is nothing. In a preferred embodiment R1 comprises or is ap peoplytide moiety covalently linked to the N-termin oaf l the sequence of formula 1.b, and / or R2 comprises o ar p isolypeptide moiety covalently linked to the Cm-teinral of the sequence of formula 1.b. In this particular casee p tholypeptide component thus comprises one or tlwanoki fng polypeptide sequences. In an embodiment the polypeptide component, wiathnk filng polypeptides at either the C-terminus or N th-e terminus or both has a maximum length of 400 am aicniods, or 350 amino acids or 300 amino acids or a 2m00ino acids, e.g. of 150 amino acids, 125 amino acids a,t o mrost 100 amino acids, or 75 amino acids oro astt m 50 amino acids. In a preferred embodiment, the polypeptide compto,n eevnen when including flanking polypeptides ath e ritthe C-terminus or the N-terminus or both, may b me o astt 100 amino acids, or 75 amino acids or at m 50os atmino acids or e.g. at most 49, 48, 47, 46, 45, 44,24,34,14, 40, 39, 38 or, if truncated, 37, 36, 35, 3334,, 32, 31, 30, or 29, 28 or 27 amino acids in length. In a particular embodiment, the polypeptide compnotn ceonsists essentially of a polypeptide having the sequence as shown in any of general formulae 1 o tro in 9 any of SEQ ID NOs: 63 to 85 or as defined an iny of paragraphs 1 to 13. Preferably, said inhibitor compound comprises ay p eopl tide component having a -CO3 R group on the Cterminus, wherein3R is selected from -OH, N4R5, wherein R4and R5are, independently, selected from H, methyl and ethyl, preferably 3 R is NH2. In a further embodiment4 R and R5 are selected from the group consisting of a conjugating moiety and a further polypeptide. In an embodiment,4R and R5are selected from methyl and ethyl. In a preferred embodiment said polypeptide compto cnoemnprises a COOH or CON2H on the C terminus. Preferably, said polypeptide component has a6Rn7N R- group on the N-terminus, wherein6 R and R7 are, independently, selected from H, methyl and ethnyl a. I further embodiment6R and R7are selected from the groupconsisting of a conjugating moiety and a furthelry p eoptide.In an embodiment, the further polypeptide seque insc aes defined herein, in particular in paragraph 16 hereinbelow. In an embodiment, the conjugating moiety is a myoi aest defined herein, in particular in paragraph 17 hereinbelow. Throughout the specification the Kv1.3 potassiuman cnhel inhibitor compound of the invention comprgisinany one of formulae, e.g. any of formulae 1 ton 5d, p aolypeptide sequences described herein, is u tond be rstood asoptionally comprising R1 and / or R2 as defined hner foeri formula 1.b. In an aspect of the invention, said Kv1.3 inhibit poorlypeptide component is a miniprotein or consists essentially of a miniprotein. Without being bound by theory, the polypeptide comnepnt or the miniprotein as defined herein compsr aiste least an alpha helix and 1 to 3 beta sheets. In a preferred embodiment, the polypeptide compto onren the miniprotein as defined herein comprise lse a sttan alpha helix and one to three beta sheets. Irnef aer pred embodiment the miniprotein comprises th sre gementshaving the following specific secondary structures: an alpha helix, preferably in positions 11 to 20, a first beta sheet, preferably in positions 259 to, a 2nd a second beta sheet, preferably in positions 326. to In a preferred embodiment, residues 11 to 20 (ipvueta atlpha helix) are non-modified proteinogenic n aomi acids. In a preferred embodiment, residues 25 to 29 (ipvueta bteta-sheet) and 32 to 36 (putative beta-sh aeret n) on-modified proteinogenic amino acids, except that Mmeaty be replaced with Nle. Without being bound by theory, in the polypeptidse d aefined herein the disulfide bridges are pre bsen twteenresidues 8 and 28, 14 and 33, and 18 and 35, wnh seareidi inhibitor compound is capable of selectiv ienlhyibiting a Kv1.3 potassium channel protein. In a preferred embodiment, in the positions whiocrhm f specific secondary structures the amino acsididu re sare proteinogenic amino acid residues. In a preferred embodiment any one of the aminos a icnid positions 1 to 38, if present, is proteinogce anmi ino acid. In a preferred embodiment, each of the am acinidos in positions 1 to 38, if present, is protegiennoic amino acid. In a preferred embodiment the Kv1.3 potassium cehla inn hibitor compound consists of proteinogenicn aomiacids. In this embodiment the Kv1.3 potassium cheal innnhibitor compound is encodable by a nucleicd. aci In an aspect of the invention, said Kv1.3 potass ciuhmannel inhibitor compound is the polypeptide comnepnt as defined in this paragraph, said polypeptide coonmepnt being a miniprotein. 1.2 The potassium channel inhibitor compound accord toin pgaragraph 1.1, wherein said polypeptide component comprises tlhloew foing amino acid sequence of formula (1) or au seenqce comprising at most 1 or 2 or 3 further mutationrse,fe prably at most 1 or 2 or 3 conservative replaecnetms: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 X X X X X X X CX X SX X CX X X C K E A GX X X G K CX NX K CX CX X X(1)(SEQ ID NO: 65) wherein, independently, X1 is any proteinogenic amino acid, or a non-prnootegienic amino acid selected from the group consgis otif Nle, sarcosine (MeGly), 2,3-diaminopropionic acDidp (r), 2,4-diaminobutyric acid (Dbu), Orn, homo-lnyesi (hLys), Nva, Abu, Aib, homo-glutamine (hGln), beta-hydroxynolrinvae (β-OH-Nva), 3-iodo-tyrosine (3I-Tyr), citrulline and a Phe derivative; or a deletion; X2 is any proteinogenic amino acid, or a non-prnootegienic amino acid selected from the group consgis otif Nle, sarcosine (MeGly), 2,3-diaminopropionic acDidp (r), 2,4-diaminobutyric acid (Dbu), Orn, homo-lnyesi (hLys), Nva, Abu, Aib, homo-glutamine (hGln), beta-hydroxynolrinvae (β-OH-Nva), 3-iodo-tyrosine (3I-Tyr), citrulline and a Phe derivative; or a deletion; X3 is any proteinogenic amino acid, or a non-prnootegienic amino acid selected from the group consgis otif Nle, sarcosine (MeGly), 2,3-diaminopropionic acDidp (r), 2,4-diaminobutyric acid (Dbu), Orn, homo-lnyesi (hLys), Nva, Abu, Aib, homo-glutamine (hGln), beta-hydroxynolrinvae (β-OH-Nva), 3-iodo-tyrosine (3I-Tyr), citrulline, pipecolic acid (Pip) or azetidine-2-cbaorxylic acid (Aze) and a Phe derivative or a deletion; X4 is any proteinogenic amino acid, or a non-prnootegienic amino acid selected from the group consgis otif Nle, Nva, Abu, Aib and beta-hydroxynorvalineβ- (OH-Nva); or a deletion; X5 is any proteinogenic amino acid, or a non-prnootegienic amino acid selected from the group consgis otif Nle, sarcosine (MeGly), 2,3-diaminopropionic acDidp (r), 2,4-diaminobutyric acid (Dbu), Orn, homo-lnyesi (hLys), Nva, Abu, Aib, homo-glutamine (hGln), beta-hydroxynolrinvae (β-OH-Nva), pipecolic acid (Pip) or azetidine-2-carboxylic acid (Aze) and 3-iodo-tyrnoesi (3I-Tyr); or a deletion; X6 is Val(V), Glu(E) or Lys(K), or a non-proteinogenic amino acid selected from g trhoeup consisting of 2,4-diaminobutyric acid (Dbu), Orn, homo-lysine y (hsL), Nva, Abu, Aib and homo-glutamine (hGln); or a deletion; X7 is Pro(P), Lys(K), Glu(E) or Ser(S), or a non-proteinogenic amino acid selected from g trhoeup consisting of 2,4-diaminobutyric acid (Dbu), Orn, homo-lysine (yhsL), homo-glutamine (hGln, ) pipecolic acid (Pip) or azetidine-2-carboxylic acid (Aze) and Aib; or a deletion; X9 is Thr(T), Lys(K), or Ser(S), or a non-proteinogenic amino acid selected from g trhoeup consisting of beta-hydroxynorvalineβ (-OH-Nva), 2,3-diaminopropionic acid (Dpr), 2,4-diianmobutyric acid (Dbu), Orn, homo- lysine (hLys) and Aib; X10 is Gly(G), His(H) or Ala, or a non-proteinogenic amino acid selected from g trhoeup consisting of sarcosine (MeGly), Abu and Aib; X12 is Pro(P), Gly(G), Lys(K) or Arg(R), or a non-proteinogenic amino acid selected from g trhoeup consisting of sarcosine (MeGly), 2,3-diaminopropionic acid (Dp 2r,)4,-diaminobutyric acid (Dbu), Orn, homo-lysineLy (hs), citrulline, pipecolic acid (Pip) and azetidine-2r-bcoaxylic acid (Aze);X13 is Gln(Q), Asp(D), Glu(E) or Asn(N), or homou-gtalmine (hGln); in particular Gln(Q) or Asp(D o),r homo-glutamine (hGln); X15 is Leu(L), Lys(K) or Val(V), or a non-proteinogenic amino acid selected from g trhoeup consisting of Nle, 2,4-diaminobutyric acid (Dbu), Orn, homo-lyesi (nhLys), Nva, Abu, Aib and homo-glutamine (hGln); X16 is Gln(Q), Glu(E) or Lys(K) or a non-proteinogenic amino acid selected from g trhoeup consisting of Orn, homo-lysine (hLys) andm hoo- glutamine (hGln); X17 is Ser(S), Lys(K) or Ala(A), or a non-proteinogenic amino acid selected from g trhoeup consisting of Aib, Abu, 2,3-diaminopropionic acid (Dpr), 2,4-diainmobutyric acid (Dbu), Orn, homo-lysine (hLys), ho-m glutamine (hGln); X23 is Met(M) or Nle; X24 is Arg(R) or Thr(T); or citrulline; or beta-hydroxynorvalineβ- (OH-Nva), X25 is Tyr(Y) or Phe(F); or a non-proteinogenic amino acid selected from g throeup consisting of 3-iodo-tyrosine (3I-Tyr) or P ahe derivative; X29 is Met(M) or Nle, X31 is Arg(R), Lys(K) or Gly(G); or a non-proteinogenic amino acid selected from g trhoeup consisting of citrulline; 2,3-diaminopropionic acid (Dpr), 2,4a-dmiinobutyric acid (Dbu), Orn, homo-lysine (hLys)d an sarcosine (MeGly); X34 is Lys(K) or Arg(R), or a non-proteinogenic amino acid selected from g trhoeup consisting of Orn, homo-lysine (hLys), citrulline; X36 is Phe(F), Tyr(Y) or Ser(S) or a non-proteinogenic amino acid selected from g trhoeup consisting of Aib, 3-iodo-tyrosine (3I-Ty arn)d a Phe derivative; X37 is Gly(G), Pro(P), preferably Gly(G), or a deletion; X38 is Lys(K), Arg(R), or a hydrophobic amino ac iind, particular Lys(K), Arg(R), or Ile(I), or a non-proteinogenic amino acid selected from g trhoeup consisting of 2,3-diaminopropionic acid (Dpr), 2,4-diaminobuty aric id (Dbu), Orn, homo-lysine (hLys), citrulline,va N or Nle;or a deletion; wherein a Phe-derivative is selected from the gr coounpsisting of - 4-fluoro-phenylalanine, - 4-amino-phenylalanine, - 4-nitro-phenylalanine, - 4-methyl-phenylalanine; wherein said inhibitor peptide comprises a moiesty de afined in paragraph 1 on the C terminus; and wherein optionally at most 5, 4, 3, 2 or 1 aminoids ac is / are alpha-methyl amino acid; wherein optionally any one of said amino acidso astit pions from 1 to 10, preferably 1 to 7, and astit pio ns 21 to24 is an N-methyl amino acid, in particular at m 5o,s 4t, 3, 2 or 1 amino acids is N-methyl amino; acid or a salt thereof,wherein said inhibitor compound is capable of steivlec ly inhibiting a Kv1.3 potassium channel prot.einIn one embodiment, the polypeptide component cosminpgri the amino acid sequence of formula (1) doets co nmoprise any further mutations. Preferably, in formula (1) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 X X X X X X X CX X SX X CX X X C K E A GX X X G K CX NX K CX CX X X(1)(as shown in SEQ ID NO: 66), independently, X1, X2, X3, X4, X5, X6, X7, X9, X10 and X12, ared aesfined above for formula (1) in paragraph 1.2; X13 is Gln(Q) or Asp(D) or homo-glutamine (hGln); X15, X16, X17, X23, X24, X25, X29, X31, X34 and X3 a6re as defined above for formula (1) in paragr 1a.p2h; X37 is Gly(G); or a deletion; X38 is Lys(K), Arg(R), or Ile(I), or a non-proteinogenic amino acid selected from g trhoeup consisting of 2,3-diaminopropionic acid (Dpr), 2,4-diaminobuty aric id (Dbu), Orn, homo-lysine (hLys), citrulline,va N or Nle;or a deletion. In a preferred embodiment, any of the amino acnids a iid polypeptide component is a proteinogenicn aomi acid or the amino acids in said polypeptide compnotn aere proteinogenic amino acids. In a preferred embodiment, said potassium channheibli itor compound has a structure according to u folarm (1.b) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 1819202122 23 24 25 262728 29 30 31 3233 34 35 36 37 38 RX X X X X X X CX X SX X CX X X C K E A GX X X G K CX NX K CX CX X X R (1.b) (as shown in SEQ ID NO: 65, preferably in SEQ ID: N 6O6, or in any SEQ ID NOs selected from the gr coounpsisting of SEQ ID NO: 67 to 85), wherein in said formula the amino acids X1 to X3re8 a s defined in paragraph 1.2, or as definedy in o afn the paragraphs 2, 3, 3.1, 4, 4.1, 5, 5.1, 6, 7, 8, 88..21,, 9, 10 or 11 hereinbelow. Throughout the specification, unless specifiede dreiffntly, R1 is a moiety covalently linked to the N-termin parle,ferably said moiety comprising a conjugatingie mtyo, a further polypeptide sequence or both; or R1 is nothing, R2 is a moiety covalently linked to the C-termin parle,ferably said moiety comprising a conjugatingie mtyo, a further polypeptide sequence or both; or R2 is nothing. In a preferred embodiment, the R1 and R2 is asne ddef iin paragraph 1.1. In an aspect of the invention, said Kv1.3 potass ciuhmannel inhibitor compound is the polypeptide comnepnt as defined herein, preferably in paragraph 1.2d, p soaliypeptide component being a miniprotein. 2.The potassium channel inhibitor compound accogrd toin any one of paragraphs 1.1 or 1.2, wherein said polypeptide component comprises tlhloew foing amino acid sequence of formula (1) or au seenqce comprising at most 1 or 2 or 3 further mutationrse,fe prably at most 1 or 2 or 3 conservative replaecnetms: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 X X X X X X X CX X SX X CX X X C K E A GX X X G K CX NX K CX CX X X(1)(SEQ ID NO: 67) whereinX1 is Gly(G) or Gln(Q) or a deletion; or a non-periontogenic amino acid selected from the group cotins gis ofsarcosine (MeGly), and homo-glutamine (hGln); X2 is Val(V), Thr(T), Lys(K), Ile(I) or Ala(A), or a deletion or a non-proteinogenic amino acid sedlec frtom the group consisting of sarcosine (MeGly), Orn, homo-lysine (hLys), N,v Aabu, Aib, homo-glutamine (hGln) and beta-hydroxryvnaoline (β-OH-Nva); X3 is Pro(P), Ile(I), Glu(E), Gly(G), Arg(R), or Tr(yY), or a deletion or a non-proteinogenic aminoid a scelected from the group consisting of Nle, sarcosine (MeGly), 2,3-diaminopropionic aciDdp (r), 2,4-diaminobutyric acid (Dbu), Orn, homo-lnyesi (hLys), Nva, Abu, Aib, homo-glutamine (hGln), beta-hydroxynolrinvae (β-OH-Nva), 3-iodo-tyrosine (3I-Tyr), citrulline, pipecolic acid (Pip), azetidine-2-carxbyolic acid (Aze) and a Phe derivative;X4 is Ile(I), Thr(T) or Ala(A) or a deletion or ao n -proteinogenic amino acid selected from the gr coounpsisting of Nle, Nva, Abu, Aib and beta-hydroxynorvalineβ- (OH-Nva); X5 is Asn(N), Pro(P) or Ser(S) or a deletion oro an- nproteinogenic amino acid selected from the gr coounpsisting of Aib, homo-glutamine (hGln), pipecolic acid (Pi apn)d azetidine-2-carboxylic acid (Aze); X6 is Val(V), Glu(E) or Lys(K), or a deletion or n aon-proteinogenic amino acid selected from thep gr coounsisting of Orn, homo-lysine (hLys), Nv,a Abu, Aib and homo-glutamine (hGln); X7 is Pro(P), Lys(K), Glu(E) or Ser(S), or a deolenti or a non-proteinogenic amino acid selected f trhoem group consisting of Orn, homo-lysine (hLys), homo-glutanme (ihGln), pipecolic acid (Pip) or azetidine-2-carboxylic acid (Aze) and Aib; X9 is Thr(T), Lys(K), or Ser(S), or a non-proteineongic amino acid selected from the group consis otifng beta-hydroxynorvalineβ (-OH-Nva), Orn, homo-lysine (hLys a)nd Aib; X10 is Gly(G), His(H) or Ala(A), or a non-proteineongic amino acid selected from the group consis otifn sgarcosine (MeGly), Abu and Aib;X12 is Pro(P), Gly(G), Lys(K) or Arg(R), or a nonro-pteinogenic amino acid selected from the groupsi csotin g ofsarcosine (MeGly), Orn, homo-lysine (hLys), citirnuell, pipecolic acid (Pip) or azetidine-2-carboxy aliccid (Aze); X13 is Gln(Q) or Asp(D); or (hGln); X15 is Leu(L), Lys(K) or Val(V), or a non-proteineognic amino acid selected from the group consis otifn Ngle, Orn, homo-lysine (hLys), Nva; X16 is Gln(Q), Glu(E) or Lys(K) or a non-proteinongice amino acid selected from the group consistifn Ogr on, homo- lysine (hLys), homo-glutamine (hGln); X17 is Ser(S), Lys(K) or Ala(A) or a non-proteinongice amino acid selected from the group consistifn Agb ou, Aib, Orn, homo-lysine (hLys); X23 is Met(M) or Nle;X24 is Arg(R) or Thr(T); or a non-proteinogenic anmoi acid selected from the group consisting of clli ntreu and beta-hydroxynorvalineβ (-OH-Nva); X25 is Tyr(Y) or Phe(F); X29 is Met(M) or Nle; X31 is Arg(R) Lys(K) or Gly(G) or a non-proteinogicen amino acid selected from the group consisting cit oruf lline, Orn, homo-lysine (hLys a)nd sarcosine (MeGly);X34 is Arg(R) or Lys(K) or a non-proteinogenic amoin acid selected from the group consisting of clit nruel, Orn,homo-lysine (hLys); X36 is Phe(F) or Tyr(Y) or Ser(S); X37 is Gly(G), Pro(P) or a deletion; X38 is Arg(R), Ile (I) or a deletion; wherein said inhibitor peptide comprises a moiesty de afined in paragraph 1.1 on the C terminus; and wherein optionally at most 5, 4, 3, 2 or 1 aminoids ac is / are alpha-methyl amino acid(s); wherein optionally any one of said amino acidso astit pions from 1 to 7, is an N-methyl amino acid, p ianrticular at most 5, 4, 3, 2 or 1 amino acids is N-methyln aom aicid; or a salt thereof,wherein said inhibitor compound is capable of steivlec ly inhibiting a Kv1.3 potassium channel prot.einIn a preferred embodiment, any of the amino acnids a iid polypeptide component is a proteinogenicn aomi acid or the amino acids in said polypeptide compnotn aere proteinogenic amino acids. In an aspect of the invention, said Kv1.3 potass ciuhmannel inhibitor compound is the polypeptide comnepnt as defined in this paragraph 1.2, said polypep ctoidmeponent being a miniprotein. In one embodiment, the polypeptide component cosminpgri the amino acid sequence of formula (1) doets no comprise any further mutations. 3. The potassium channel inhibitor compound accnogrd ainy one of paragraphs 1.1, 1.2 or 2, wherein said polypeptide component comprises thlloew foing amino acid sequence of formula (1): wherein, independently, X1 is Gly(G) or Gln(Q), or a deletion; X2 is Val(V), Thr(T), Lys(K), Ile(I) or Ala(A), or a deletion; X3 is Pro(P), Ile(I), Glu(E), Gly(G), Tyr(Y) or Ar(gR), or a deletion; X4 is Ile(I), Thr(T) or Ala(A), or a deletion; X5 is Asn(N), Pro(P) or Ser(S), or a deletion; X6 is Val(V), Glu(E) or Lys(K), or a deletion; X7 is Pro(P), Lys(K), Glu(E) or Ser(S), or a deolent;i X9 is Thr(T), Ser(S), Lys(K), preferably Thr(T) S orer(S); X10 is Gly(G), His(H) or Ala(A), preferably Gly(G o)r His(H); X12 is Pro(P), Lys(K), Arg(R) or Gly(G); X13 is Gln(Q) or Asp(D), preferably Gln(Q); X15 is Leu(L), Lys(K) or Val(V); preferably Leu(L);X16 is Gln(Q), Glu(E) or Lys(K); preferably Gln(Q o)r Lys(K);X17 is Ser(S), Lys(K) or Ala(A), preferably Ser( oSr) Lys(K); X23 is Met(M) or Nle; X24 is Arg(R) or Thr(T); X25 is Tyr(Y) or Phe(F); X29 is Met(M) or Nle; X31 is Gly(G), Arg(R) or Lys(K), preferably Arg(R o)r Lys(K); X34 is Lys(K) or Arg(R); X36 is Phe(F) or Tyr(Y) or Ser(S), preferably Ph)e o(Fr Tyr(Y); X37 is Gly(G), Pro(P) or a deletion; preferably G(Gly); X38 is Arg(R) or Ile(I), preferably Arg(R), or al deetion; wherein said amino acid sequence preferably comespr CisOOH or CONH2 on the C terminus; or a salt thereof,wherein said inhibitor compound is capable of steivlec ly inhibiting a Kv1.3 potassium channel prot,einpreferably having a relative binding selectivitylu vea of at least 3 over both Kv1.2 and Kv1.1 proste mineasured by phage display, wherein preferably relative selectivity is theo ra otif the binding measure, preferably absorbancuee vsa Kl v1.3 / Kv1.2 or Kv1.3 / Kv1.1 (the higher the better). In an alternative embodiment, the inhibitor compdou conmprises a conjugating moiety or a further peoplytpide moiety either at the N-terminus (R1) or at the Crm-tienus (R2) of the amino acid sequence or at both. Preferably, in formula (1) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 X X X X X X X CX X SX X CX X X C K E A GX X X G K CX NX K CX CX X X(1)(as shown in SEQ ID NO: 69), independently, X1, X2, X3, X4, X5, X6 and X7 are as defined abo fovre formula (1) in paragraph 3; X9 is Thr(T) or Ser(S), X10 is Gly(G) or His(H), X12 is Pro(P), Lys(K), Arg(R) or Gly(G), X13 is Gln(Q), X15 is Leu(L), X16 is Gln(Q) or Lys(K), X17 is Ser(S) or Lys(K), X23 is Met(M) or Nle, X24 is Arg(R) or Thr(T), X25 is Tyr(Y) or Phe(F), X29 is Met(M) or Nle, X31 is Arg(R) or Lys(K), X34 is Lys(K) or Arg(R), X36 is Phe(F) or Tyr(Y), X37 is Gly(G), X38 is Arg(R), or a deletion. 3.1. In a highly preferred embodiment, in the psoituams channel inhibitor compound said polypeptide component comprises the amino s aecqiduence selected from the group consisting of the following amino acid sequences: SEQ ID NO: 1, SEDQ N IO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: S 5E,Q ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: S 9E,Q ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID N 1O6:, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ N IDO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29,Q S IED NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ IDNO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO:, 3 S6EQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID N 4O3:, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ N IDO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56 a SnEdQ ID NO: 57. In an aspect of the invention, said Kv1.3 potass ciuhmannel inhibitor compound is the polypeptide comnepnt as defined in paragraph 3, including 3.1, said peoplytide component being a miniprotein. 4. The potassium channel inhibitor compound accnogrd toi any one of paragraphs 1.1, 1.2, 2, 3 or 3.1, wherein said polypeptide component comprises thlloew foing amino acid sequence of formula (2) 1 2 3 4 5 6 7 8 9 10 11 12 13 1415 16 17 181920 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 X X X X X X X CX X SX X C LX X C K E A GX X X G K CX NX K CX CX X X(2)(SEQ ID NO: 70) wherein X1 is Gly(G), Gln(Q) or a deletion; X2 is Val(V), Thr(T), Lys(K), or Ile(I), or a deleiotn; X3 is Pro(P), Ile(I), Glu(E), Gly(G), Tyr(Y) or Ar(gR), or a deletion; X4 is Ile(I), Thr(T) or a deletion; X5 is Asn(N), Pro(P) or Ser(S), or a deletion; X6 is Val(V), Glu(E) or Lys(K); X7 is Pro(P), Lys(K), Glu(E) or Ser(S), preferab Plryo(P), Lys(K) or Glu(E);X9 is Thr(T), Ser(S) or Lys(K), preferably Thr(T o)r, Ser(S);X10 is Gly(G) or His(H), preferably Gly(G); X12 is Pro(P), Lys(K), Arg(R) or Gly(G), preferab Plyro(P), Lys(K) or Arg(R), X13 is Gln(Q) or Asp(D), preferably Gln(Q);X16 is Gln(Q), Glu(E) or Lys(K); preferably Gln(Q o)r Lys(K);X17 is Ser(S) or Lys(K), preferably Ser(S); X23 is Met(M) or Nle; X24 is Arg(R) or Thr(T); X25 is Tyr(Y) or Phe(F), preferably Tyr(Y); X29 is Met(M) or Nle; X31 is Arg(R) or Gly(G); X34 is Lys(K) or Arg(R); X36 is Phe(F) or Tyr(Y), preferably Phe(F); X37 is Gly(G) or Pro(P), or a deletion, preferably Gly(G) or a dieolne;t X38 is Arg(R) or a deletion; or a salt thereof,wherein said inhibitor compound is capable of steivlec ly inhibiting a Kv1.3 potassium channel prot.einPreferably said inhibitor compound has an inhibnit sioelectivity value of at least 100 over both Kv1 a.n2d Kv1.1 proteins, preferably as measured by a patch-clamp method, wherein preferably selectivity is IC50[Kv1.x] / IC5K0v[1.3] and is assessed as a value over both Kv1.2 and.1 Kv1 proteins. In a preferred embodiment said amino acid sequ ceonmceprises COOH or CON2H on the C terminus. In a further preferred embodiment, the inhibitorm cpoound comprises a conjugating moiety and / or ahe furrtpolypeptide moiety either at the N-terminus (R1) at o trhe C-terminus (R2) of the amino acid seque onrc aet both.Preferably, in formula (2) (as shown in SEQ ID NO: 71), independently X1 is Gly(G), Gln(Q) or a deletion, X2 is Val(V), Thr(T), Lys(K), or Ile(I), or a deleiotn, X3 is Pro(P), Ile(I), Glu(E), Gly(G), Tyr(Y) or Ar(gR), or a deletion, X4 is Ile(I), Thr(T) or a deletion, X5 is Asn(N), Pro(P) or Ser(S), or a deletion, X6 is Val(V), Glu(E) or Lys(K); X7 is Pro(P), Lys(K) or Glu(E); X9 is Thr(T), or Ser(S), X10 is Gly(G), X12 is Pro(P), Lys(K) or Arg(R), X13 is Gln(Q), X16 is Gln(Q) or Lys(K); X17 is Ser(S), X23 is Met(M) or Nle, X24 is Arg(R) or Thr(T), X25 is Tyr(Y), X29 is Met(M) or Nle, X31 is Arg(R) or Gly(G), X34 is Lys(K) or Arg(R), X36 is Phe(F), X37 is Gly(G) or a deletion, X38 is Arg(R) or a deletion. 4.1. In a highly preferred embodiment in the poiutamss channel inhibitor compound said polypeptide component comprises the amino s aecqiduence selected from the group consisting of the following amino acid sequences: SEQ ID NO: 2, SEDQ N IO: 5, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO:, 12 SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 22, SEQ N IDO: 26, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 32, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36,Q S IED NO: 37, SEQ ID NO: 38, SEQ ID NO: 48, SEQ IDNO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO:, 5 S2EQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQID NO: 56 and SEQ ID NO: 57. In an aspect of the invention, said Kv1.3 potass ciuhmannel inhibitor compound is the polypeptide comnepnt as defined in this paragraph 4, including 4.1, spaoildypeptide component being a miniprotein. 5. The potassium channel inhibitor compound accnogrd toi any one of paragraphs 1.1, 1.2, 2, 3, or 4, wherein said polypeptide component comprises thlloew foing amino acid sequence of formula (3) wherein X1 is Gly(G) or Gln(Q), or a deletion, X2 is Val(V), Ile(I), Thr(T), or a deletion,X3 is Pro(P), Ile(I), Glu(E), Gly(G) or Tyr(Y), o ar deletion,X4 is Ile(I), Thr(T) or a deletion, X5 is Asn(N) or Ser(S), or a deletion, X6 is Val(V), Glu(E) or Lys(K), X7 is Pro(P), Lys(K) or Glu(E), X9 is Thr(T) or Ser(S), X12 is Pro(P), Lys(K) or Arg(R), X13 is Gln(Q) or Asp(D), preferably Gln(Q),X16 is Gln(Q), Glu(E) or Lys(K); preferably Gln(Q o)r Lys(K),X17 is Ser(S) or Lys(K), preferably Ser(S), X23 is Met(M) or Nle, X24 is Arg(R) or Thr(T), X25 is Tyr(Y) or Phe(F), preferably Tyr(Y), X29 is Met(M) or Nle, X31 is Arg(R) or Gly(G), X34 is Lys(K) or Arg(R), X36 is Phe(F) or Tyr(Y), preferably Phe(F),X37 is Gly(G) or Pro(P), or a deletion, preferably Gly(G) or a dieolne,tX38 is Arg(R) or a deletion; or a salt thereof,wherein said inhibitor compound is capable of steivlec ly inhibiting a Kv1.3 potassium channel prot,einPreferably said inhibitor compound has an inhibnit sioelectivity value of at least 1000 over both K2v1 a.nd Kv1.1 proteins, preferably as measured by a paltacmh-pc method. In a preferred embodiment, said amino acid sequ ceonmceprises COOH or CON2H on the C terminus. In a further preferred embodiment, the inhibitorm cpoound comprises a conjugating moiety or a furtherpolypeptide moiety either at the N-terminus (R1) at o trhe C-terminus (R2) of the amino acid seque onrc aet both.Preferably, in formula (3) (as shown in SEQ ID NO: 73), independently, X1 is Gly(G) or Gln(Q), or a deletion, X2 is Val(V), Ile(I), Thr(T), or a deletion,X3 is Pro(P), Ile(I), Glu(E), Gly(G) or Tyr(Y), o ar deletion,X4 is Ile(I), Thr(T) or a deletion, X5 is Asn(N) or Ser(S), or a deletion, X6 is Val(V), Glu(E) or Lys(K), X7 is Pro(P), Lys(K) or Glu(E), X9 is Thr(T) or Ser(S), X12 is Pro(P), Lys(K) or Arg(R), X13 is Gln(Q), X16 is Gln(Q) or Lys(K); X17 is Ser(S), X23 is Met(M) or Nle, X24 is Arg(R) or Thr(T), X25 is Tyr(Y), X29 is Met(M) or Nle, X31 is Arg(R) or Gly(G), X34 is Lys(K) or Arg(R), X36 is Phe(F), X37 is Gly(G) or a deletion, X38 is Arg(R) or a deletion. 5.1 In a highly preferred embodiment in the potuamss cihannel inhibitor compound said polypeptide comprises the amino acid sequ seenlceected from the group consisting of the follow ainmgino acid sequences: SEQ ID NO: 9, SEQ ID NO: 11, SEQ NO ID: 17, SEQ ID NO: 20, SEQ ID NO: 22, SEQ ID NO6:, 2 SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 32, SEQ N IDO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 48, SEQ ID NO: 49,Q S IED NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55 and SEQ ID N 5O7.: In an aspect of the invention, said Kv1.3 potass ciuhmannel inhibitor compound is the polypeptide comnepnt as defined in this paragraph 5, including 5.1, spaoildypeptide component being a miniprotein. 6. The potassium channel inhibitor compound accnogrd ainy one of paragraphs 1.1, 1.2, 2, 3, 4 or 5, wherein said polypeptide comprises the followingin aom acid sequence having formula (4) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 X X X X X X X CX G SX X C LX X C K E A GX X X G K CX NX K CX C FX X(4)(SEQ ID NO: 74) wherein X1 is Gly(G) or Gln(Q), or a deletion, X2 is Val(V), Ile(I) or Thr(T), or a deletion,X3 is Pro(P), Ile(I), Glu(E), Gly(G) or Tyr(Y), o ar deletion,X4 is Ile(I) or Thr(T), preferably Ile, X5 is Asn(N) or Ser(S), X6 is Val(V), Glu(E) or Lys(K), X7 is Pro(P), Lys(K) or Glu(E), X9 is Thr(T) or Ser(S), X12 is Pro(P), Lys(K) or Arg(R), X13 is Gln(Q) or Asp(D), preferably Gln(Q),X16 is Gln(Q), Glu(E) or Lys(K); preferably Gln(Q o)r Lys(K); in particular Gln(Q),X17 is Ser(S) or Lys(K), preferably Ser(S), X23 is Met(M) or Nle, X24 is Arg(R) or Thr(T), X25 is Tyr(Y) or Phe(F), X29 is Met(M) or Nle, X31 is Arg(R) or Lys(K) X34 is Lys(K) or Arg(R), X37 is Gly(G) or a deletion, X38 is Arg(R) or a deletion, or a salt thereof,wherein said inhibitor compound is capable of steivlec ly inhibiting a Kv1.3 potassium channel prot.einPreferably, in formula (4) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 X X X X X X X CX G SX X C LX X C K E A GX X X G K CX NX K CX C FX X(4)(as shown in SEQ ID NO: 75), independently, X1, X2, X3, X5, X6, X7, X9 and X12 are as definebdo ave for formula (4) in this paragraph 6, X4 is Ile(I), X13 is Gln(Q), X16 is Gln(Q) or Lys(K); in particular Gln(Q), X17 is Ser(S), X23 is Met(M) or Nle, X24 is Arg(R) or Thr(T), X25 is Tyr(Y) or Phe(F), X29 is Met(M) or Nle, X31 is Arg(R) or Lys(K) X34 is Lys(K) or Arg(R), X37 is Gly(G) or a deletion, X38 is Arg(R) or a deletion. In particular, in formula (4) X16 is Gln(Q) (SEQ I NDO: 76). In an aspect of the invention, said Kv1.3 potass ciuhmannel inhibitor compound is the polypeptide comnepnt as defined in this paragraph 6, said polypeptidmep coonent being a miniprotein. 7. The potassium channel inhibitor compound accnogrd toi any one of paragraphs 1.1, 1.2, 2, 3, 4r, 65, owherein said polypeptide comprises the followingin aom acid sequence having formula (5) wherein X1 is Gly(G) or Gln(Q), or a deletion, X2 is Val(V) or Thr(T), or a deletion,X3 is Pro(P), Ile(I), Glu(E), Gly(G) or Tyr(Y), o ar deletion,X5 is Asn(N) or Ser(S); X6 is Val(V), Glu(E) or Lys(K); X7 is Pro(P), Lys(K) or Glu(E); X9 is Thr(T) or Ser(S), X12 is Pro(P), Lys(K) or Arg(R), X16 is Gln(Q) or Lys(K), in particular Gln(Q), X17 is Ser(S), Lys(K), preferably Ser(S), X23 is Met(M) or Nle, X24 is Arg(R) or Thr(T), X25 is Tyr(Y) or Phe(F), X29 is Met(M) or Nle, X31 is Arg(R) or Lys(K), X34 is Lys(K) or Arg(R), X37 is Gly(G) or a deletion, X38 is Arg(R) or a deletion, wherein preferably said inhibitor peptide compri CseOsOH or CONH2 on the C terminus; or a salt thereof,wherein said inhibitor compound is capable of steivlec ly inhibiting a Kv1.3 potassium channel proteinpreferably with a selectivity as given in any oef t phrevious paragraphs. Preferably, in formula (5) (as shown in SEQ ID NO: 78), independently, X1, X2, X3, X5, X6, X7, X9 and X12 are as definebdo ave for formula (5) in this paragraph 7, X16 is Gln(Q), X17 is Ser(S),X23, X24, X25, X29, X31, X34, X37 and X38 are asfin de d above for formula (5) in this paragraph 7.In an aspect of the invention, said Kv1.3 potass ciuhmannel inhibitor compound is the polypeptide comnepnt as defined in this paragraph 7, said polypeptidmep coonent being a miniprotein. 8. The potassium channel inhibitor compound accnogrd toi any one of paragraphs 1.1, 1.2, 2, 3, 4, o 5r, 76, wherein said polypeptide comprises the followingin aom acid sequence having formula 6) wherein X1 is Gly(G) or Gln(Q), or a deletion, X2 is Val(V) or Thr(T), or a deletion,X3 is Pro(P), Ile(I), Glu(E), Gly(G) or Tyr(Y), o ar deletion,X9 is Thr(T) or Ser(S), X16 is Gln(Q) or Lys(K), in particular Gln(Q), X17 is Ser(S) or Lys(K), preferably Ser(S), X23 is Met(M) or Nle, X24 is Arg(R) or Thr(T), X25 is Tyr(Y) or Phe(F), preferably Tyr(Y), X29 is Met(M) or Nle, X31 is Arg(R) or Lys(K), X34 is Lys(K) or Arg(R), X37 is Gly(G) or a deletion, X38 is Arg(R) or a deletion, or a salt thereof, or in particular X16 is Gln(Q), and X17 is Ser(Sn)d a X25 is Tyr(Y) (as shown in SEQ ID NO: 80),wherein said inhibitor compound is capable of steivlec ly inhibiting a Kv1.3 potassium channel prot;einor preferably (as shown in SEQ ID NO: 81) X1 is Gly(G) or Gln(Q) or a deletion, X2 is Val(V) or Thr(T), or a deletion, X3 is Pro(P), Glu(E), Gly(G) or a deletion, X9 is Thr(T), or Ser(S), X16 is Gln(Q) or Lys(K), in particular Gln(Q), X17 is Ser(S), Lys(K), preferably Ser(S), X23 is Met(M) or Nle, X24 is Arg(R) or Thr(T), X25 is Tyr(Y), X29 is Met(M) or Nle, X31 is Arg(R) or Lys(K), X34 is Lys(K) or Arg(R), X37 is Gly(G) or a deletion, X38 is Arg(R) or a deletion, or a salt thereof, or in particular X16 is Gln(Q), and X17 is Ser(Sas) ( shown in SEQ ID NO: 82).wherein said inhibitor compound is capable of steivlec ly inhibiting a Kv1.3 potassium channel prot,einpreferably with a selectivity as given in any oef t phrevious paragraphs. Preferably, said amino acid sequence comprises CO orO CHONH2on the C terminus. In an aspect of the invention, said Kv1.3 potass ciuhmannel inhibitor compound is the polypeptide comnepnt as defined in this paragraph 8, said polypeptidmep coonent being a miniprotein. 8.1. The potassium channel inhibitor compound adcicnogr to any one of the paragraphs 1.1, 1.2, 2,d 33 a.1n, selected from an inhibitor compound comprising aly p eoptide component having an amino acid sequenceselected from the group of amino acid sequencesis ctoinng of sequences having SEQ ID NOs: 1 to 57,or sequences comprising at most 1 or 2 or 3 fur mthuetrations, preferably at most 1 or 2 or 3 consteivreva replacements. 8.2. The potassium channel inhibitor compound adcicnogr to any one of the paragraphs 4 and 4.1, 55 a.1n,d 6 and 6.1 selected from an inhibitor compound comprising aly p eoptide component having an amino acid sequenceselected from the group consisting of the follow ainmgino acid sequences: SEQ ID NO: 2, SEQ ID NO S:E 5Q, ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 1 S7E,Q ID NO: 20, SEQ ID NO: 22, SEQ ID NO: 26, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 32, SEQ ID N 3O4:, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 48, SEQ ID NO: 49, SEQ N IDO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55 and SEQ ID NO: 57, or sequences comprising at most 1 or 2 or 3 fur mthuetrations, preferably at most 1 or 2 or 3 consteivreva replacements. 9. The potassium channel inhibitor compound accnogrd toi any one of paragraphs 1, 1.1, 2, 3, 4, 5 or 6 wherein said polypeptide comprises the followingin aom acid sequence having formula (7): 1 2 3 4 5 6 7 8 9 1011121314151617181920212223242526272829303132333435363738 X1X2X3X4X5X6X7C X9G S X12Q C L X16X17C K E A G X23X24X25G K C X29N R K C K C F G X38(7) (SEQ ID NO: 83) wherein, X1 is Gly(G), Gln(Q), or a deletion; X2 is Val(V), or Ile(I), or a deletion; X3 is Pro(P), Glu(E), Tyr(Y), or a deletion; X4 is Ile(I), Thr(T), or a deletion; X5 is Asn(N), Ser(S), or a deletion; X6 is Val(V), or Lys(K); X7 is Pro(P), Lys(K), or Glu(E); X9 is Thr(T), or Ser(S); X12 is Pro(P), or Lys(K); X16 is Gln(Q), Glu(E) or Lys(K);X17 is Ser(S), or Lys(K);X23 is Met(M) or Nle; X24 is Arg(R) or Thr(T); X25 is Tyr(Y) or Phe(F);X29 is Met(M) or Nle;X38 is Arg(R) or a deletion; or a salt thereof, wherein preferably said polypeptide component coismepsr COOH or CONH2on the C terminus,wherein said inhibitor compound is capable of steivlec ly inhibiting a Kv1.3 potassium channel prot.einPreferably, the inhibitor compound selectively b inihtsi Kv1.3 over Kv1.1 and / or Kv1.2 by a factor otf le aast 10000. 10. The potassium channel inhibitor compound acincogr tdo paragraph 9, wherein said polypeptide comepnotn comprises the following amino acid sequence of fuolarm (8): 1 2 3 4 5 6 7 8 9 1011121314151617181920212223242526272829303132333435363738 G V X3I N V X7C X9G S P Q C L X16X17C K E A G X23X24Y G K C X29N R K C K C F G X38(8) (SEQ ID NO: 84) wherein, X3 is Pro(P), or Glu(E); X7 is Pro(P), or Lys(K); X9 is Thr(T), or Ser(S);X16 is Gln(Q), or Lys(K);or a salt thereof. wherein preferably said polypeptide component coismepsr COOH or CONH2 on the C terminus,wherein said inhibitor compound is capable of steivlec ly inhibiting a Kv1.3 potassium channel prot.einPreferably, the inhibitor compound selectively b inihtsi Kv1.3 over Kv1.1 and / or Kv1.2 by a factor otf le aast 50000. 11 The potassium channel inhibitor compound accnogrd toi any of the previous paragraphs, in partic pualarragraph 10, wherein said polypeptide component comprises fo tlhlowing amino acid sequence of formula (9): 1 2 3 4 5 6 7 8 9 1011121314151617181920212223242526272829303132333435363738 G V P I N V P C T G S P Q C L X16 S C K E A G M X24 Y G K C M N R K C K C F G X38 (9) (SEQ ID NO: 85); or a salt thereof. wherein preferably said polypeptide component coismepsr COOH or CONH2on the C terminus,wherein said inhibitor compound is capable of steivlec ly inhibiting a Kv1.3 potassium channel prot.ein 12. The potassium channel inhibitor compound acincogr tdo any one of paragraphs 1.1, 1.2, 2, 3, 3,.14,.14, 5, 5.1 or 6, having a sequence selected from the group congsi osfti:n VGINVKCTGSKQCLQSCKEAGMTYGKCMNRKCKCYPR (SEQ ID NO 9,) TIINEKCSGSRDCLQSCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO 1),1 TIINEKCTGSKQCLQSCKEAGMTYGKCMNGKCRCF (SEQ ID NO 12), QIYTSKECTGSKQCLQSCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO71), GVEINVKCSGSPQCLQSCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO02), GVPINVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO2) 2, TIINEKCTGSKQCLQSCKEAGMRYGKCMNGKCRCF (SEQ ID NO 26), GVPINVPCTGSPQCLQSCKEAGMTYGKCMNGKCKCFGR (SEQ ID NO9) 2, GVPINVPCTGSPQCLQSCKEAGMRFGKCMNRKCKCFGR (SEQ ID NO0) 3, GVPINVPCTGSPQCLQSCKEAGMRYGKCMNRKCKCFGR (SEQ ID NO2) 3, GVPINVPCTGSPQCLESCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO4) 3, GVPINVPCTGSPQCLKSCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO53), GVPINVPCTGSPQCLQKCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO63), INVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO 37), VPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO 38), GVPINVPCTGSPQCLQSCKEAG(Nle)RYGKC(Nle)NRKCKCFGam-ide^(SEQ ID NO 48), GVPINVPCTGSPQCLQSCKEAGMRYGKCMNRKCKCFGRam- ide^(SEQ ID NO 49), GVPINVPCTGSPQCLQSCKEAGMRYGKCMNRKCKCFGa-mide (SEQ ID NO 50), GVPINVPCTGSPQCLQSCKEAGMRYGKCMNRKCKCFG (SEQ ID NO) 5,1 GVPINVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGRa-mide (SEQ ID NO 52), GVPINVPCTGSPQCLQSCKEAG(Nle)RYGKC(Nle)NRKCKCF^G (SEQ ID NO 53), GVPINVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFG (SEQ ID NO) 5,4 GVPINVPCTGSPQCLQSCKEAG(Nle)TYGKC(Nle)NRKCKCFGR (SE IQD NO 55), and GVPINVPCTGSPQCLKSCKEAGMRYGKCMNRKCKCFGa-mide (SEQ ID NO 57); or a salt thereof. Preferably, the inhibitor compound selectively b inihtsi Kv1.3 over Kv1.1 and / or Kv1.2 by a factor otf le aast 2000. 12.1. The potassium channel inhibitor compoundr adcincgo to paragraph 12, having a sequence selected from the group congsi osfti:n QIYTSKECTGSKQCLQSCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO71), GVEINVKCSGSPQCLQSCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO02), GVPINVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO2) 2, GVPINVPCTGSPQCLQSCKEAGMRFGKCMNRKCKCFGR (SEQ ID NO0) 3, GVPINVPCTGSPQCLESCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO4) 3, GVPINVPCTGSPQCLKSCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO53), GVPINVPCTGSPQCLQKCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO63), INVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO 37), VPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO 38), GVPINVPCTGSPQCLQSCKEAG(Nle)RYGKC(Nle)NRKCKCFGam-ide^(SEQ ID NO 48), GVPINVPCTGSPQCLQSCKEAGMRYGKCMNRKCKCFGRam- ide^(SEQ ID NO 49), GVPINVPCTGSPQCLQSCKEAGMRYGKCMNRKCKCFGa-mide (SEQ ID NO 50), GVPINVPCTGSPQCLQSCKEAGMRYGKCMNRKCKCFG (SEQ ID NO) 5,1 GVPINVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGRa-mide (SEQ ID NO 52), GVPINVPCTGSPQCLQSCKEAG(Nle)RYGKC(Nle)NRKCKCF^G (SEQ ID NO 53), GVPINVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFG (SEQ ID NO) 5,4 GVPINVPCTGSPQCLQSCKEAG(Nle)TYGKC(Nle)NRKCKCFGR (SE IQD NO 55), and GVPINVPCTGSPQCLKSCKEAGMRYGKCMNRKCKCFGa-mide (SEQ ID NO 57); or a salt thereof. Preferably, the inhibitor compound selectively b inihtsi Kv1.3 over Kv1.1 and / or Kv1.2 by a factor otf le aast 10000. 12.2. The potassium channel inhibitor compoundr adcincgo to paragraph 12.1, GVEINVKCSGSPQCLQSCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO02), GVPINVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO2) 2, GVPINVPCTGSPQCLKSCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO53), GVPINVPCTGSPQCLQKCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO63), GVPINVPCTGSPQCLQSCKEAGMRYGKCMNRKCKCFGa-mide (SEQ ID NO 50), GVPINVPCTGSPQCLQSCKEAGMRYGKCMNRKCKCFG (SEQ ID NO) 5,1 GVPINVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGRa-mide (SEQ ID NO 52), GVPINVPCTGSPQCLQSCKEAG(Nle)RYGKC(Nle)NRKCKCF^G (SEQ ID NO 53), GVPINVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFG (SEQ ID NO) 5,4 GVPINVPCTGSPQCLQSCKEAG(Nle)TYGKC(Nle)NRKCKCFGR (SE IQD NO 55), and GVPINVPCTGSPQCLKSCKEAGMRYGKCMNRKCKCFGa-mide (SEQ ID NO 57); or a salt thereof. Preferably, the inhibitor compound selectively b inihtsi Kv1.3 over Kv1.1 and / or Kv1.2 by a factor otf le aast 50000. 13. The potassium channel inhibitor compound acincogr tdo any of the previous paragraphs, said inohrib citompound having the sequence GVPINVPCTGSPQCLQSCKEAGMTYGKCMKNCRKCFGR (SEQ ID NO 22); or a salt thereof, having the sequence GVPINVPCTGSPQCLQSCKEAGMRYGKCMKNCRKCFGR-amide^(SEQ ID NO 49); or a salt thereof, having the sequence GVPINVPCTGSPQCLQSCKEAGMRYGKCMKNCRKCFG-amide (SEQ ID NO 50); or a salt thereof, having the sequence GVPINVPCTGSPQCLQSCKEAGMRYGKCMKNCRKCFG (SEQ ID NO 51); or a salt thereof. having the sequence GVPINVPCTGSPQCLQSCKEAGMTYGKCMKNCRKCFGR-amide (SEQ ID NO 52); or a salt thereof, or having the sequence GVPINVPCTGSPQCLKSCKEAGMRYGKCMKNCRKCFG-amide (SEQ ID NO 57); or a salt thereof. 14. The potassium channel inhibitor compound acincogr tdo any one of paragraphs 1.1, 1.2, 2, 3, 3,.14,.14, 5, 5.1, 6, 7 8, 8.1, 8.2, 9, 10, 11, 12, 12.1, 12.2 or 13, said potassium channel inhibitor compound consgist einssentially of the Kv1.3 inhibitor polypeptide component or a salt thereof.14.1 In a particular embodiment, said Kv1.3 inhoibr i ptolypeptide component is as defined in any oidf p sa ragraphswith the proviso that it does not comprise a furrt ahmeino acid or peptide. In a particular embodiment, said Kv1.3 inhibitorly ppoeptide component is as defined in any of saridag praaphs with the proviso that it does not comprise a furrt choenjugating moiety. 15. The potassium channel inhibitor compound acincogr tdo any one of paragraphs 1.1, 1.2, 2, 3, 3,.14,.14, 5, 5.1, 6, 7, 8, 8.1, 8.2, 9, 10, 11, 12, 12.1, 12.2, 13, o 1r41.4.1, wherein the polypeptide component is a minipro oterin which consists essentially of a miniprotein. The miniprotein of the invention has a fold comipnrgis an alpha helix and 1-3 beta sheets. In a particular embodiment the miniprotein has f tehaetures as defined in paragraph 1.1. In particular, the fold of the miniprotein of thnev iention comprises three disulfide linkages, praebfelyr between cysteins 8 and 28, 14 and 33, as well as 18 an rde 3sp5e,ctively. 16 The potassium channel inhibitor compound accnogrd toi any one of paragraphs 1.1, 1.2, 1.3, 2,13,, 43,.5, 6, 7, 8, 8.1, or 9, comprising additional amino acid sequences N-tearml ain d / or C-terminal of the Kv1.3 inhibitor componnt.ePreferably the inhibitor compound comprises a fnus piorotein, said fusion protein comprising the Kv1.3 inhibitor polypeptide component and a fusion parr.tn Pereferably the inhibitor compound is a fusionot perincomprising the Kv1.3 inhibitor polypeptide compont ean d the fusion partner.In a particular embodiment the fusion protein csotnss oif proteinogenic amino acids. In a particular embodiment the fusion protein icso ednable by a nucleic acid. Preferably the potassium channel inhibitor compou isnd a fusion protein comprising the polypeptidecomponent having Kv1.3 inhibitor activity and thuesi fon partner is one or more further peptide ory p eopl tide orprotein. The one or more fusion partners may ber re df to as heterologous components.In a preferred embodiment the one or more furtheeprti pde or polypeptide or protein is - a binding polypeptide molecule, in particular - an antibody or antibody fragment wherein one ore m coormplementarity-determining regions (CDRs) comprise a peptide sequence derived from a potmas cshiuannel inhibitor, characterized in that the peptide sequence is incorporated into at least C oDnRe of the antibody,- an Fc fusion protein, which involves linking thely ppoeptide having Kv1.3 inhibitor activity to the Fc region of an antibody to enhance stability andm se hrualf-life, - an antibody analog, like a minibody or an antic,alin - a polypeptide to facilitate recombinant express liiokne, a signal peptide, - a polypeptide, to increase solubility or extendf- hliafel in vivo, e.g. an albumin fusion or other albumin- binding moiety designed to extend the half-life th oef compound,- a polypeptide to facilitate purification or a la,b leikle a polypeptide tag like a His-tag or a Mycg-,ta - a linker peptide between the Kv1.3 inhibitor polpyptidee component and the heterologous component. In a preferred embodiment the fusion protein can ex bperessed in an expression system from a singclle i ncuacid encoding the fusion protein. In an embodiment, the Kv1.3 inhibitor polypeptidoem cponent may also be inserted within a heterologous polypeptide, which may be regarded as a “scaff fooldr” the Kv1.3 inhibitor polypeptide. In such cas tehse, ion channel inhibitor compound may be considered to compristeer hoelogous components N- and C-terminal of the K3v1.inhibitor, wherein the heterologous components d aerreived from the same molecule and interact witeh a on other, e.g. to fold into a single scaffold, having the K.3v1 inhibitor displayed at its surface. Such scadff molay be that of a binding molecule. For example, the Kv1.3 inhibitor may be insertedth wini a surface loop of a heterologous protein, i en.tgo. the CDR sequence of an antibody or an antibody frag,m lieknet an Fc fragment, containing the antigen bningd diomain. In certain embodiment, the size of the Kv1.3 poiutamss channel inhibitor compound may be e.g. at m 2o0s0t kDa, or 180 kDa or at most 160 kDa. In preferred embodiments the fusion partners aned p tohlypeptide component are smaller and may have a maximum length of 400 amino acids, or 350 aminods ac oir 300 amino acids or 200 amino acids, amindos a,c ei.g. of 150 amino acids, 125 amino acids, or at most 10i0no am acids, or 75 amino acids or at most 50 aminidos a.c In an embodiment the polypeptide component, evethn f wlainking polypeptides at either the C-terminurs th oe N-terminus or both may be at most 100 amino ac oirds 7,5 amino acids or at most 50 amino acids o.r a et. mg ost 49, 48, 47, 46, 45, 44, 43, 42, 41, 40, 39, 38 or,u infc tated, 37, 36, 35, 34, 33, 32, 31, 30, or 29 o,r 2287 amino acids. In a particular embodiment the fusion protein ha -sCO aR3group on the C terminus, wherein3i Rs selected from -OH, NR4R5, wherein R4and R5are, independently, selected from H, methyl anhdyl, e ptreferably R3is NH2. Ina further embodiment 4 R and R5 are selected from the group consisting of a coantjiung moiety and a furtherpolypeptide. In a preferred embodiment said fus piroontein comprises a COOH or CON2H on the C terminus. In a particular embodiment the fusion protein hnas R6aR7N- group on the N-terminus, wherein6a Rnd R7are, independently, selected from H, methyl and ethnyl a. I further embodiment6R and R7are selected from the groupconsisting of a conjugating moiety and a furthelry p eoptide.In a particular embodiment the fusion protein irsth feur conjugated as specified in paragraph 17.17 The potassium channel inhibitor compound accnogrd toi any one of paragraphs 1.1, 1.2, 2, 3, 4, 57, 68, 8.1, 9,10, 11, 12, 12.1, 12.2, 13, 15 or 16, which is a polypeptide conjugate. In a preferred embodiment, wherein the inhibitomr cpo und is a polypeptide conjugate, either R1 or is R a2conjugating moiety. In a particular embodiment the R1 group is linkoed th te polypeptide via the N-terminal amine group th oef polypeptide. In a further particular embodiment, the R2 grou lpin iksed to the polypeptide via the C-terminal canryblo group, e.g. by an amide bond. Preferably, the conjugating moiety comprises at phreotsic group which is selected from the group csotninsgi of- a stabilizing moiety, e.g. moieties that increahse c tirculatory half-life, e.g. a polymer, such aosly pethyleneglycol (PEG), - a moiety to set solubility, e.g. a moiety is preafbelry selected from - a lipid or lipidoid, particularly for enhancing mebmrane permeability or association, - a small molecule designed to improve solubility a olterr pharmacokinetics, - a sugar moiety such as polysaccharide to improavbeili styt and solubility, - a targeting agent, preferably selected from - polysaccharides, - lipids or lipoids allowing cell surface targeting, - nucleic acids, - binding molecules e.g. binding proteins, like aondtiibes or artificial antibody analogs, e.g. aptam, ers anticalins, minibodies or the like, to direct thoem cpound to specific cell types or tissues- labels or tags allowing detection of the inhibi ctor mpound, for example visualization agents, prebfleyr saelectedfrom fluorescent labels, radiolabels, magneticn reasnoce imaging labels, and agents enabling ind liarebcetling by high affinity binding to labeling molecules; - tags facilitating purification of the conjugatekse li affinity labels or peptide tags. In a particular embodiment R1 or R2 in formula 1 is.b t.he conjugating moiety. According to a further preferred embodiment of p thre sent invention, the conjugate comprises oneo orre mlinker(s) preferably one or more spacer(s) betw tehen polypeptide of the invention and the prosth gertoicup.Preferably, the conjugate comprises one or morkeer li(ns) and optionally one or more spacer(s) betw theenpolypeptide of the invention and the prostheticu gpr.o In a particular embodiment the linkers are poaf r tthe R1 and R2 moieties of formula 1.b. The invention also relates to the following pharmeuatcical compositions. 18. A pharmaceutical composition comprising thea pssoitum channel inhibitor compound according to a onf yparagraphs 1 to 17, preferably 1.1, 1.2, 2, 35, 46, 7, 8, 8.1, 8.2, 9, 10, 11, 12, 12.1, 12.2,, 1143. 14.1, 15 or 16 anda pharmaceutically acceptable excipient or carrier. In an aspect of the invention, the polypeptide conmepnt in the potassium channel inhibitor compourn tdhe opotassium channel inhibitor compound in the pharemuatic al composition is a miniprotein.In a particular embodiment the potassium channheibl i tnor compound itself is a miniprotein.In a preferred embodiment, the pharmaceutical cosmitipoon is formulated with a polymer that facilitaste controlled or slow release of the active ingred.ie Fnotr example, the composition may comprise po-lyla(cdtlide-co- glycolide) (PLGA), which is recognized for its aibtyil to provide a sustained release of the compo Tunhdis. allows for maintaining therapeutic levels of the drug in thoedy b over an extended period without repeated do.sing In a further preferred embodiment, the pharmacaelu ctiocmposition is formulated as polymeric micropicalerts (MPs). In a preferred embodiment, the pharmaceutical cosmitipoon is formulated for parenteral administrati fon rinjection, preferably wherein said pharmaceuticoaml p cosition is formulated for subcutaneous, intracmuulasr or intravenous injection. Preferably, it is formulat feodr subcutaneous injection. In a further preferred embodiment, the pharmacaelut cicomposition is formulated for inhalation, preafbelry wherein said pharmaceutical composition is formeudla ftor intranasal or pulmonary administration. The invention also relates to the potassium cha inn heiblitor compounds and the pharmaceutical comtipoonsifor use as medicaments and in particular in thleow foinlg conditions. 19. The potassium channel inhibitor compound acincogrd to any of paragraphs 1 to 17 or the pharmacaeluti composition according to paragraph 18, for use m ased aicament. The potassium channel inhibitor compound accord toin agny of paragraphs 1 to 17 or the pharmaceu ctoicmalposition according to paragraph 18, for use in parenteraelf,e prably subcutaneous administration. The potassium channel inhibitor compound accord toin agny of paragraphs 1 to 17 for use in in vivo diagnosis carried out on human or animal body. 19.1 The potassium channel inhibitor compound adcincogr to any of paragraphs 1 to 17 or the pharmaiccaelut composition according to paragraph 18, for use in the treatment or prevention of a dise oars deisorder in a subject.Preferably the subject diagnosed as having ant el dev leavel of Kv1.3 channel protein.The level of Kv1.3 channel protein in this cont iesx tto be understood as the amount of Kv1.3 cha pnrnoetelins that can be measured in a sample, either withienll a or c on the surface of a cell, i.e. embeddedhe in c tell membrane. Preferably the level of Kv1.3 channel protein isa msuered on the surface of a cell involved in diseaseprogression. Such cells are for example but noit e lidm to: T lymphocytes, B lymphocytes, macrophag aedsip,ocytes,smooth muscle cells and various tumor cells. Preferably, the disorder or disease is a T cellia mted disorder, preferably an effector memory Tl ( cTeelmcell) mediated disorder. In a preferred embodiment the Kv1.3 channel pro itse oinverexpressed in said cells. Preferably, the subject is diagnosed with a T m cel dl iated disorder.Preferably, the inhibitor compound selectively b inihtsi Kv1.3 over Kv1.1 and / or Kv1.2, preferably ov beorth, by a factor of at least 1000. Preferably, the inhibitor compound selectively b inihtsi Kv1.3 over Kv1.1 and / or Kv1.2, preferably ov beorth, by a factor of at least 2000. Preferably, the inhibitor compound selectively b inihtsi Kv1.3 over Kv1.1 and / or Kv1.2, preferably ov beorth, by a factor of at least 10000. Preferably, the inhibitor compound selectively b inihtsi Kv1.3 over Kv1.1 and / or Kv1.2, preferably ov beorth, by a factor of at least 50000. 19.2 The potassium channel inhibitor compound adcincogr to any of paragraphs 1 to 17 or the pharmaiccaelut composition according to paragraph 17, for usen in in a vivo diagnosis of a disease or disorder in a subject. Preferably the subject diagnosed as having ant el dev leavel of Kv1.3 channel protein.In a preferred embodiment th ine vivo diagnosis is carried out by administering thes psoituam channel inhibitorcompound according to any of paragraphs 1 to 1 s7a tido subject, and by detecting the binding of s inahidibitorcompound to the Kv1.3 channel protein in the bofd sya oid subject. 20. The potassium channel inhibitor compound acincogrd to any of paragraphs 1 to 17 or the pharmacaeluti composition according to paragraph 18, or said cooumnpd or composition for use according to paragr 1a9p,h for use in the treatment or prevention or i ann vivo diagnosis of an inflammatory disease or disord iner, particular chronic inflammatory diseases, includ ainugtoimmune diseases. 20.1 In a particularly preferred embodiment, threo cnhic inflammatory disorder is selected from theou gpr consisting of type I diabetes mellitus, multiple sclerosiss,t seymic lupus erythematosus, rheumatoid arthritsiso,ri patic arthritis, psoriasis, , inflammatory bowel disease (includ Cinrgohn's disease and ulcerative colitis), autoimm tuhnyeroiditis(including Hashimoto's thyroiditis and Graves' daise ), vitiligo, alopecia areata, scleroderma, amumtouine hepatitis,ankylosing spondylitis, chronic obstructive pulmoryna disease (COPD), asthma, atopic dermatitis, hdiednraitis suppurativa, fibromyalgia, sarcoidosis, Behçets'sea dsie, pemphigus vulgaris, Guillain-Barré syndr,om yeasthenia gravis, idiopathic thrombocytopenic purpura, priyma briliary cholangitis, hay fever, anaphylaxis, arglliec rhinitis, urticaria, eczema, dermatomyositis, inclusion bo mdyyositis, polymyositis, vasculitis, Sjogren's syonmdre, uveitis, lung fibrosis, cirrhosis, chronic inflammatory deemliynating polyneuropathy, erythema, thyroiditisl,er aglic contactdermatitis, glomerulonephritis, inflammatory boneeso rrption, transplant rejection, and graft-versous t-h disease.Preferably, the inflammatory disorder or diseas ae T is cell mediated disorder, preferably an effec mtoermory T cell (Tem cell) mediated disorder. 20.2 The potassium channel inhibitor compound adcincogr to any of paragraphs 1 to 17 or the pharmaiccaelut composition according to paragraph 18, or said cooumnpd or composition for use according to paragr 1a9p,h for use in the treatment or prevention of an immlougniocal disorder.Preferably, the immunological disorder is an infmlaamtory disorder or an autoimmune disorder, more preferably a T cell-mediated inflammatory disord mero,re preferably an effector memory T cell (Teml) c melediated immunological or inflammatory disorder. More preafbelry, the Tem cell-mediated inflammatory disordser a i Temcell-mediated chronic inflammatory disorder.In a particular embodiment, the Tem cell-mediatherdon cic inflammatory disorder is an autoimmune ddiseor.r In a particularly preferred embodiment, the Teml-m ceeldiated chronic inflammatory disorder is seledc ftreom the group consisting of type I diabetes mellituus,lt miple sclerosis, systemic lupus erythematosuesu,m rhatoid arthritis, psoriatic arthritis, psoriasis, inflammatory bow deilsease (including Crohn's disease and ulceratiovleitis c), autoimmune thyroiditis (including Hashimoto's thiydriotis and Graves' disease), vitiligo, alopeciaa atare, scleroderma, autoimmune hepatitis, ankylosing spondylitis, saidrocsois, Behçet's disease, pemphigus vulgaris, a Ginu-iBllarré syndrome, myasthenia gravis, idiopathic thrombopceyntoic purpura, primary biliary cholangitis, dermmatyoositis,inclusion body myositis, polymyositis, vasculit Sisj,ogren's syndrome, uveitis, lung fibrosis, chro ini fclammatorydemyelinating polyneuropathy, thyroiditis, glomeornuelphritis, inflammatory bone resorption, transpt l raenjection, graft-versus-host disease, asthma, and atopic dtietirsm (eaczema). 21. The potassium channel inhibitor compound acincogrd to any of paragraphs 1 to 17 or the pharmacaeluti composition according to paragraph 18, or said cooumnpd or composition for use according to paragr 1a9p,h for use in the treatment or prevention of neoplasm. In a particular embodiment the neoplasm is a ca,n ec.ge.r a carcinoma, sarcoma, lymphoma or leukemia. The cancer treated by the compound according to of a pnayragraphs 1 to 17 or the pharmaceutical comitiopnos according to paragraph 10 includes but is not e limdit o breast cancer, prostate cancer, lymphomahs a ssuc non- Hodgkin lymphoma (NHL), T-cell lymphoma, preferab aly cutaneous T-cell lymphoma or muscle sarcoma. Preferably the neoplasm, preferably cancer is chtearriazed by an elevated level of Kv1.3 channele pirno.t Highly preferably Kv1.3 is overexpressed in thec cearn cells; in particular, Kv1.3 overexpressiono isrre clating with disease progression. 22. The potassium channel inhibitor compound acincogrd to any of paragraphs 1 to 17 or the pharmacaeluti composition according to paragraph 18, or said cooumnpd or composition for use according to paragr 1a9p,h for use in the treatment or prevention of a neuflraominmatory or neurological disorder, preferably a ce Tll mediated neurological disorder and / or a microgliead-miated neurological disorder. Preferably the neuroinflammatory disorder or neougroiclal disorder is characterized by an elevatedel le ovf Kv1.3 channel protein in the cells associated w thiteh disease. Highly preferably Kv1.3 is overexpressed in thels ce alssociated with the disease; in particular, K3v1. overexpression is correlating with disease progiorens.s In a particularly preferred embodiment, neuroinfmlaamtory or neurological disorder is selected frome g throup consisting of multiple sclerosis, Alzheimer's disease, Parkinsso dnis'ease, amyotrophic lateral sclerosis (ALS),neuromyelitis optica, autoimmune encephalitis, Glaiunil-Barré syndrome, chronic inflammatory demyetliin gapolyneuropathy, myasthenia gravis, Lambert-Eatonas mthyenic syndrome, stiff person syndrome, paranaesoticpl neurological syndromes, autoimmune epilepsy, ahnedr o dtisorders following viral infections. 23. The potassium channel inhibitor compound acincogrd to any of paragraphs 1 to 17 or the pharmacaeluti composition according to paragraph 18, or said cooumnpd or composition for use according to paragr 1a9p,h for use in the treatment or prevention of condistio anssociated with weight management, such as t ininhgibi weight gain, promoting weight loss, reducing exc beosdsy weight, and treating obesity-related condnistio includingobesity-linked inflammation, gallbladder diseasre o,b oesity-induced sleep apnea.The potassium channel inhibitor compound accord toing any of paragraphs 1 to 17 or the pharmaceutical composition according to paragraph 18, or said cooumndp or composition for use according to paragr 1a9p,h for use in the treatment or prevention of conditions cau bsyed or associated with impaired glucose controcl,h s aus metabolicsyndrome, insulin resistance, glucose intolera pnrcee-,diabetes, increased fasting glucose level tsy,p oer 2 diabetes.The potassium channel inhibitor compound accord toing any of paragraphs 1 to 17 or the pharmaceutical composition according to paragraph 18, or said cooumndp or composition for use according to paragr 1a9p,h for usein the treatment or prevention of smooth musclelif pero ative and / or migration disorders such as rneossteis,particularly in patients following vascular surgeesri like angioplasty. The invention also relates to the followi inng vitro diagnostic uses. 24. Use of the potassium channel inhibitor compo aucncdording to any of paragraphs 1 to 17 in in a vnitro diagnosis of a subject. Preferably the disease or disorder is as define adny in of paragraphs 19 to 23. Preferably, in the disorder or disease the Kv1v.3el le is elevated. Preferably, the Kv1.3 level is measured by conntagc ctiells of a subject, preferably cell, optiona inlly a tissue, obtained from a subject, with said potassium chlan innheibitor compound, and by detecting the bindi onfg said inhibitor compound, preferably a labeled or tagg inehdibitor compound to the cells or tissues(s). In a particular embodiment the Kv1.3 level is mereadsu by a method as defined in any of paragraph tso 278 for in vitro diagnosis. 24.1 Use of the potassium channel inhibitor compdo aucncording to any of paragraphs 1 to 17 in a mde ftohro in vitro diagnosis of a disease or disorder. Preferably, the disorder or disease is a T cellia mted disorder, preferably an effector memory Tl ( cTeelmcell) mediated disorder. 25. The invention also relates to uses of the psoiutmas channel inhibitor compound in diagnosis ofio vuasr disease. 25.1 Use of the potassium channel inhibitor compdo aucncording to any of paragraphs 1 to 17 in a mde ftohro in vitro diagnosis of an inflammatory disease or disordne pr,a irticular chronic inflammatory diseases or ddiseorsr, including autoimmune diseases. In a particularly preferred embodiment, the chro in filcammatory disease or disorder is selected f trhoem groupconsisting of type I diabetes mellitus, multiplele srocsis, systemic lupus erythematosus, rheumatrothidrit ais, psoriatic arthritis, psoriasis, , inflammatory bowel disea (isnecluding Crohn's disease and ulcerative colit aisu),toimmunethyroiditis (including Hashimoto's thyroiditis an Gdraves' disease), vitiligo, alopecia areata, scdle rrmoa, autoimmunehepatitis, ankylosing spondylitis, chronic obstrivuect pulmonary disease (COPD), asthma, atopic deitrism,at hidradenitis suppurativa, fibromyalgia, sarcoid,o Bsieshçet's disease, pemphigus vulgaris, Guillaainrr-éB syndrome, myasthenia gravis, idiopathic thrombocytopenic puurarp, primary biliary cholangitis, hay fever, analpahxyis, allergic rhinitis, urticaria, eczema, dermatomyositis, insciolun body myositis, polymyositis, vasculitis, Sjeong'rs syndrome, uveitis, lung fibrosis, cirrhosis, chronic inflamtmoary demyelinating polyneuropathy, erythema, thdyirtoisi, allergic contact dermatitis, glomerulonephritis, inflammayto brone resorption, transplant rejection, and gvreafrts-us-host disease Preferably, the inflammatory disorder or diseas ae T is cell mediated disorder, preferably an effec mtoermory T cell (Tem cell) mediated disorder. 25.2 Use of the potassium channel inhibitor compdo aucncording to any of paragraphs 1 to 17 in a mde ftohro in vitro diagnosis of an immunological disorder. Preferably, the immunological disorder is an infmlaamtory disorder or an autoimmune disorder, more preferably a T cell-mediated inflammatory disord mero,re preferably an effector memory T cell (Teml) c melediated immunological or inflammatory disorder. More preafbelry, the Tem cell-mediated inflammatory disordser a i Tem cell-mediated chronic inflammatory disorder. In a particular embodiment, the Tem cell-mediatherdon cic inflammatory disorder is an autoimmune ddiseor.r In a particularly preferred embodiment, the Teml-m ceeldiated chronic inflammatory disorder is seledc ftreom the group consisting of type I diabetes mellitus, mpulelti sclerosis, systemic lupus erythematosus, rhteouidma rthritis, psoriatic arthritis, psoriasis, inflammatory bow deilsease (including Crohn's disease and ulceratiovleitis c), autoimmune thyroiditis (including Hashimoto's thiydriotis and Graves' disease), vitiligo, alopeciaa atare, scleroderma, autoimmune hepatitis, ankylosing spondylitis, chicron obstructive pulmonary disease (COPD), asthmoap,ic at dermatitis, fibromyalgia, sarcoidosis, Behçet'sea dsise, pemphigus vulgaris, Guillain-Barré syndrom yea,sthenia gravis, idiopathic thrombocytopenic purpura, priyma briliary cholangitis, hay fever, anaphylaxis, arglliec rhinitis, urticaria, eczema, dermatomyositis, inclusion bo mdyyositis, polymyositis, vasculitis, Sjogren's syonmdre, uveitis, lung fibrosis, cirrhosis, chronic inflammatory deemliynating polyneuropathy, erythema, thyroiditisl,er aglic contactdermatitis, glomerulonephritis, inflammatory boneeso rrption, transplant rejection, and graft-versous t-h disease,asthma, and atopic dermatitis (eczema). 25.3 Use of the potassium channel inhibitor compdo aucncording to any of paragraphs 1 to 17 in a mde ftohro in vitro diagnosis of neoplasm, preferably cancer, includ biuntg not limited to breast cancer, prostate can ocre lry,mphomas such as non-Hodgkin lymphoma (NHL), T-cell lympho,m pareferably a cutaneous T-cell lymphoma or muscle sarcoma. In a particular embodiment the neoplasm is a ca,n ec.ge.r a carcinoma, sarcoma, lymphoma or leukemia. Preferably the neoplasm, preferably cancer isa cchtear ized by an elevated level of Kv1.3 channetle pinro.Highly preferably Kv1.3 is overexpressed in thec cearn cells; in particular, Kv1.3 overexpressiono isrre clating with disease progression. 25.4 Use of the potassium channel inhibitor compdo aucncording to any of paragraphs 1 to 17 in a mde ftohro in vitro diagnosis of a neuroinflammatory or neurologicaslo drdier, preferably a T cell mediated neurologicisaolr dder or a microglia-mediated neurological disorder. Preferably the neuroinflammatory disorder or neougroiclal disorder is characterized by an elevatedel le ovf Kv1.3 channel protein in the cells associated w thiteh disease. Highly preferably Kv1.3 is overexpressed in thels c aeslsociated with the disease; in particular, K3v o1v.erexpression is correlating with disease progression. In a particularly preferred embodiment, the T c (eplrleferably Tem cell) mediated neuroinflammatory or neurological disorder is selected from the grounps cisoting of multiple sclerosis, Alzheimer's disease, Parkinsson' disease, amyotrophic lateral sclerosis (ALS), nmeuyreolitis optica, autoimmune encephalitis, GuillaBina-rré syndrome, chronic inflammatory demyelinating poluyrnoepathy, myasthenia gravis, Lambert-Eaton myasicthen syndrome, stiff person syndrome, paraneoplasticro nloeguical syndromes, autoimmune epilepsy, and o dthiseorrders following viral infections. 25.5 Use of the potassium channel inhibitor compdo aucncording to any of paragraphs 1 to 17 in a mde ftohro in vitro diagnosis of a condition associated with weighta mgaenment, such as inhibiting weight gain, promo wtinegight loss, reducing excess body weight, and treating obeseiltayt-erd conditions including obesity-linked inflamtmioan, gallbladder disease, or obesity-induced sleep a.pnea Use of the potassium channel inhibitor compoundor adcincg to any of paragraphs 1 to 17 in a method in for vitro diagnosis of a condition caused by or associatiethd i wmpaired glucose control, such as metabolicd sroymne,insulin resistance, glucose intolerance, pre-deiasb,e int creased fasting glucose levels, or typeb 2e dteias.Use of the potassium channel inhibitor compouncdor adcing to any of paragraphs 1 to 17 in a methord in fo vitro diagnosis of smooth muscle proliferative and / ogrr matiion disorders such as restenosis, particu ilnar plyatients following vascular surgeries like angioplasty. 26. The invention relates to the following usesr wehine binding of any of the potassium channel inthoirb ciompounds of the invention is detected. 26.1 The use according to any of paragraphs 245, to in 2 particular paragraphs 25.1 to 25.5, wherheein b tinding of said potassium channel inhibitor compound is dedte.ct In a particular embodiment in any of the diseasre dsis oorders the level of Kv1.3 is elevated in comrispoan with a normal level. Preferably, the normal level ise urnsdtood as a range of Kv1.3 levels measured inth hye saulbjects. 26.2 The use according to any of paragraphs 245, t ion 2 particular paragraphs 25.1 to 25.5, or paarpahgr 26.1, whereinsaid potassium channel inhibitor compound compr ais deestectable label.The invention also relates to the followi inng vitro diagnostic methods. 27. A method for the in vitro diagnosis of a disease or disorder defined in o afn pyaragraphs 19 to 23 or any of paragraphs 24 to 25 in a subject, wherein said method comprises the following steps: − providing a biological sample obtained from saibdje suct, said sample comprising expressed Kv1.3 psioutmas channel proteins, − adding a potassium channel inhibitor compound adcincgor to any of paragraphs 1 to 17 to the sample to contact the inhibitor compound with the Kv1.3 postiuams channel proteins, −detecting binding of the potassium channel inhirb cito mpound to the Kv1.3 potassium channel proteins.Preferably, the diagnostic method further compr tihses steps of − quantifying the binding of the potassium channehlib initor compound to the Kv1.3 potassium channel proteins, wherein the level of binding correlateisth w the level of the expressed Kv1.3 potassium n cheal n proteins in the sample,− comparing the level of the expressed Kv1.3 potamss cihuannel proteins in the sample with a refereenvce l, l− if the level of the expressed Kv1.3 potassium chealn pnroteins in the sample is higher than a refeere lenvcel, considering the subject as having the diseaseia thgeno dsis of which was expected or assumed. In an embodiment the reference level is provided ca bryrying out parallel steps in a reference sample. In particular, in this embodiment the method comsepsri the following steps: − providing a reference sample, said sample optiyon caollmprising a reference level of Kv1.3 potassium channel proteins, − adding a potassium channel inhibitor compoundr adcincgo to any of paragraphs 1 to 17 to the reference sample, − detecting binding of the potassium channel inhrib cito mpound to the Kv1.3 potassium channel proteins.28. The in vitro diagnostic method according to paragraph 27, winhe thre disease or disorder is selected from diseaseand disorders as defined in any paragraphs he inre pina,rticular selected from the group consisting ofdiseases or disorders listed in paragraph 19, diseases or disorders listed in paragraph 20, diseases or disorders listed in paragraph 21, diseases or disorders listed in paragraph 22 diseases or disorders listed in paragraph 23 diseases or disorders listed in paragraph 24, diseases or disorders listed in paragraph 25. The invention also relates to a nucleic acid molleec euncoding potassium channel inhibitor compound, iparticular a fusion protein part thereof, provid theadt it consists of proteinogenic amino acids; aesll w as vectors andcells for expression of said nucleic acid. 29. The invention also relates to a nucleic acidle mcuole encoding potassium channel inhibitor compdo aucncordingto any of paragraphs 1 to 17,wherein each of the amino acid residues of thes psoiutam channel inhibitor compound is a proteinoge anmicino acid residue, preferably as defined in any of paragraphs 1 to 17. In an embodiment the nucleic acid molecule enco ade fussion protein comprising the polypeptide of the invention. Preferably the fusion protein is defin ined paragraph 16. 30. A vector comprising the nucleic acid molecucleco arding to paragraph 29. Preferably, the vector is an expression vector.31. A cell comprising the nucleic acid moleculeo arcdcing to paragraph 29 or the vector (preferablpyr e sxsion vector)according to paragraph 30. Preferably, the cell is a host cell. The invention also relates to the following meth fod r the preparation of the potassium channel intohribicompound of the invention. 32. The invention also relates to a method foru pcroindg a potassium channel inhibitor compound acicnogr tdo any of paragraphs 1 to 17, wherein the compounds are prepared by a recomb oinra snytnthetic production method. Preferably, the recombinant method is recombinaunclte nic acid technology. Preferably, the synthetic production method isp ati pde synthesis method. For example, an ion channel blocker peptide ma syy bnethesized by a method which comprises(a) synthesizing the peptide by means of solid-phase liq ourid-phase peptide synthesis methodology andrecovering the peptide thus obtained; (b) expressing the peptide from a nucleic acid contstr huact encodes the peptide and recovering the essxiporne product; or(c) expressing a precursor peptide from a nucleic c aocnidstruct that encodes the precursor peptide secequ, enrecovering the expression product, and modifyineg p threcursor peptide to yield an ion channel bloc okfer the invention.33. The invention also relates to methods for pcroindgu a potassium channel inhibitor compound of in thve ntion.33.1. A method for producing a potassium channheibl in tor compound according to any of paragraphos 17 t,wherein each of the amino acid residues of thes psoiutam channel inhibitor compound is a proteinoge anmicino acid residue, and wherein any conjugating moiety, ifs pernet, also consist of proteinogenic amino acidd ruees(is); wherein said method comprises the steps of culturing a ( cperellferably a host cell) according to paragraph, s 3a1id cell comprising the nucleic acid molecule accordinga troa pgraph 29 or the vector (preferably expressiocnto vr)e according to paragraph 30, under conditions allowing the esxspiron of the potassium channel inhibitor compo furonmd said nucleic acid molecule, and recovering the produ pcoetdassium channel inhibitor compounds from theu crue.lt In an embodiment the nucleic acid molecule enco thdes fusion protein as defined in paragraph 16.33.2 A method for producing a potassium channeilb in tohr compound according to any of paragraphs 17 t,o saidmethod comprising the synthetic production of thoeta pssium channel inhibitor compound by any suita pbelpetide synthesis method. In an embodiment, the peptide synthesis methodm iosc F-amino acids peptide chemistry or solid-phaspetid pesynthesis.33.3 A method for producing a potassium channeibl in tohr compound according to any of paragraphs 17 t,owherein said potassium channel inhibitor compousn ad p iolypeptide conjugate,said method comprisingpreparing the polypeptide as defined accordingny to o af paragraphs 1 to 17 by a peptide synthesisho mde,t and conjugating the conjugating moiety to the polypdeep.ti 34. The invention also relates to therapeutic mdesth uosing the potassium channel inhibitor compoufn thde o invention. In particular, the therapeutic method is a methfo tdre oatment carried out on the body of the patie i.en.t, the subject in need of such treatment. A method of treatment of a disease or disorder isnub aject, wherein said method comprises adminnisgte trhie potassium channel inhibitor compound accordingn tyo o af paragraph 1 to 17 or the pharmaceutical cosmitipoon according to claim 18 to the subject. Preferably, the disease or disorder is selectemd f throe group consisting of diseases and disordsetresd li in anyof paragraphs 19 to 25. In a particular embodiment, the subject is an anl,im praeferably a vertebrate, in particular a mamm Maol.re preferably, the subject is a human. Preferably, the compound is administered parenlyte troal the subject in need thereof. Preferably, the compound is administered subcutuasnlyeo to the subject in need thereof. Preferably, following administration of the inhiobrit compound to said subject, the inhibitor compou isnd capable of selectively inhibiting a Kv1.3 potassi cuhmannel protein. 34.1. The invention also relates to a combinedn doiasgtic and therapeutic methods, wherein, a disease or disorder is diagnoses in a subjeecfte,r parbly by a method according to any of claims to 2247, said disease or disorder being selected from thouep gr consisting of diseases and disorders liste adn iyn of paragraphs 19 to 25, and wherein said subject is diagnosed to have saidas deise or disorder, treating said subject by admirninisgte the potassium channel inhibitor compound accordingn tyo o af paragraph 1 to 17 or the pharmaceutical cosmitipoonaccording to claim 18 to said subject. Prefera ibnly t,he diagnostic and / or therapeutic methods of in thve ntion thelevel of selectivity of the inhibitor compounds a is defined in paragraph 19.1.The invention also relates to the following meth fo rd measuring Kv1.3 channel protein levels.35. A method for measuring Kv1.3 channel protevine le in a sample, wherein said method comprises fo tlhloewingsteps:− providing a sample, said sample comprising Kv1.t3as psoium channel proteins, − adding a potassium channel inhibitor compound adcincogr to any of paragraphs 1 to 17 to the samp cleon totact the inhibitor compound with the Kv1.3 potassiumn cnheal proteins, −detecting binding of the potassium channel inhrib cito mpound to the Kv1.3 potassium channel proteins.Preferably, the method further comprises the s otefps − quantifying the binding of the potassium channehlib initor compound to the Kv1.3 potassium channetle pinros, wherein the level of binding correlates with thvee lle of the expressed Kv1.3 potassium channel pnrsot ieni the sample, −comparing the level of the expressed Kv1.3 potamss cihuannel proteins in the sample with a refereenvce l, l− if the level of the expressed Kv1.3 potassium cheal n pnroteins in the sample is higher than a refeere lenvcel, considering the subject as having the diseaseia thgeno dsis of which was expected or assumed. In an embodiment the reference level is provided ca bryrying out parallel steps in a reference sample. In particular, in this embodiment the method comsepsri the following steps: − providing a reference sample, said sample optiyon caolml prising a reference level of Kv1.3 potassiuhman cnel proteins, − adding a potassium channel inhibitor compoundr adcincgo to any of paragraphs 1 to 17 to the refere snacmeple, − detecting binding of the potassium channel inhrib cito mpound to the Kv1.3 potassium channel proteins. As understood herein, a reference to a paragracplhud iens a reference to its subparagraph as wel.l; a e.greference to paragraph 1 is understood as a recfer toen any one of paragraphs 1.1 and / or 1.2 ore are rnecfe to paragraph12 is understood as a reference to any one of r paaprhasg 12.11 and / or 12.2, throughout the specioficna.ti DEFINITIONS The terms "polypeptide” refers to a polymer of aom aincids of any length. The term also encompass aems ainno acid polymer that has been modified; for exampilseu,l dfide bond formation, glycosylation, lipidatio mn,ethylation, acetylation, phosphorylation, substitution by aneor,th e.g. non-natural amino acid or any other malantipioun, such as conjugation with a labeling component.The term “protein” refers to a polypeptide whichs h aa 3-dimensional (3D) structure of fold, whichf pereablycomprises at least two secondary structure elem, pernetfserably selected from beta strands and alpehlicae hs. The term “miniprotein” refers to a polypeptide o-1f 01 kDa, which has a 3-dimensional (3D) structufr feol od. Preferably, a miniprotein comprises at least twcoo snedary structure elements, preferably selectemd f broeta strandsand alpha helices, however, which has a limitede. s Iinz a particular embodiment miniproteins have le at st 10,preferably at least 25 or at least 30 amino acsidid ruees. In a particular embodiment miniproteinse ha tv most 100, preferably at most 70 or at most 50 amino acidd rueessi. As used herein the term "amino acid" includes naaltu arnd unnatural or synthetic amino acids. In c oafse proteins expressed by a living organism the amcinidos a are preferably protein forming amino acids. u Assed herein, the one-letter symbols for protein forming aminoid a rcesidues are: A (alanine); R (arginine); N (araspgaine); D (aspartic acid); C (cysteine); Q (glutamine); Eu (tagml ic acid); G (glycine); H (histidine); I (isolceiune); L (leucine); K (lysine); M (methionine); F (phenylalanine); Pro (pline); S (serine); T (threonine); V (valine); Wtry (ptophan); and Y (tyrosine). The skilled person will understand that non-prot feoirnming amino acids may also be applied in these pnret polypeptides of the invention as far as they mainin tthae structure and properties of the Kv1.3 inthoirbyi miniproteins of the invention. Such non-protein forming (non-tperinoogenic) amino acids include e.g. norleucine m.o Are detailed teaching about non-proteinogenic amino acids ca fnou bned in the detailed description of the inven.tion The term “amino acid” includes the term “amino a rceidsidue” as well. An amino acid residue refers an to amino acid as being present in a polypeptide. W twheon or more amino acids are condensated to formep atid pe, theelements of water are removed, and what remain esac ohf amino acid, i.e. units of a peptide chain ca, l ilsed an amino-acid residue. However, for the sake of the pre dsen sctription, such residues may be called aminos a rceifderring tothe skilled person’s knowledge of the chemistryin bde.h The term “conservative replacement” (or a conseivreva mt utation or a conservative substitution) is a amninoacid replacement in a protein that changes a g aivmein o acid to a different amino acid with similaior c bhemicalproperties (e.g. functional group, charge, aromitay,tic hydrophobicity, effect on secondary structu er.eg,. on rotation angles and size). In a particular embodiment, conservative subsotitnusti as considered as substitutions within thew foinllog classes on the basis of their structure and ther gael cnhemical characteristics of their side cha (Rins groups). Class Amino acids 1-letter code Aliphatic Glycine, Alanine, Valine, Leucine, Isolceiune G, A, V, L, I Hydroxyl or sulfur / selenium- Serine, Cysteine, Selenocysteine, Threonine, S, C, U, T, M containing Methionine Cyclic Proline P Aromatic Phenylalanine, Tyrosine, Tryptophan F, W Y, Basic Histidine, Lysine, Arginine H, K, R Acidic and their amides Aspartate, Glutamate, Aasgpianre, Glutamine D, E, N, Q Heterocycle Tryptophan, Histidine W, H Charged side chain Lysine, Arginine, Aspartate,ta Gmluate K, R, D, E Alternatively, conservative substitutions may befin deed based on their effect of protein stability.g,. e as mutation having a low destabilizing effect as diebsecdr in Table 1 o [fPechmann S, 201].4 In a broader sense conservative mutations alsuod inec ml utations to non-proteinogenic amino acidsh wh airce considered as usual replacements or analogs foterin porogenic amino acids e.g. as disclosed hereionw b.el “Sequence identity” is related to sequence homol coogmyparisons of sequences which may be conducted byeye, or more usually, with the aid of readily aavbaliel sequence comparison programs. These commlyer acvial ilablecomputer programs may calculate percent (%) homyo bloegtween two or more sequences and may alsoa catelc tuhle sequence identity shared by two or more amino a ocrid nucleic acid sequences. Sequence homologies b meay generated by any of a number of computer progranmoswn k in the art, for example BLAST or FASTA, etcx.a Emples of software that may perform sequence comparisnocnlusd ie, but are not limited to, the BLAST and FAS pTaAckages [Ausubel F.M. et al., 199]9 and [Altschul S.F. et al., 19]90 and the GENEWORKS suite of comparison tools. Both BLAST and FASTA are available for offline and onelin searching (see Ausubel et al., 19 ib9i9d, pages 7-58 to 7-60). Technology of computing sequence identity is wenlolw kn in the art. Sequence homology comparisons of sequences prov aid teosol to extend the inventive idea to other miniproteins having homologous sequence and the s foalmd as defined in the Brief description of thneve intion or in the appended claims. The numbering of the residues of the polypeptidfes the o invention is in accordance with the full lethng sequence of the peptides, e.g. according to SEQ NO ID: 22. For example, "X1" in the specification rresfe to the glutamine residue at position 1 or C8 is a consteivreva cysteine in position 8, whereas X34 can beti mpluel amino acids in the sequence between C33 and C35, irrteivsepe ocf whether the N-terminal of the peptide iusn tcrated. Deletion of any of the amino acids from this seqcuee dnoes not modify the numbering. “Deletion” of an amino acid residue in a polypepetid s understood herein as the removal or lacki odf a smaino acid residue in comparison with a reference seqeu.e Tnrcuncation means deletion from either the N-tinearml or the C- terminal end of the polypeptide. “Replacement”, in particular “amino acid replacemt”e isn used herein in the same meaning as “subisotnitu otfan amino acid residue” in a polypeptide, and ise ursntdood herein as the replacement of said amindo r aecsi due by achemically different amino acid residue. “Variant” of a peptide is typically a similar butiff derent, e.g. a mutant version thereof. Variant a onf amino acid in a given position is an amino acid by wh iitch can be substituted in accordance with the prte isnevnention.Preferably said variant is prepared by human incte iorna.Deletions, replacement or substitutions or addsit,io onr preparation of variants, can be carriedy opuitca tlly by peptide synthesis methods or, if said peptide e ispa prred by recombinant nucleic acid technology, r boyte pin engineering methods. As used herein the term "wild type" is a term oef t ahrt understood by skilled persons and meansyp thicea tlform of an organism, strain, gene or character aisstic it occurs in nature as distinguished from mtu otarn variant forms. The term “wild-type” relates to a protein, a nucle aicid or a sequence thereof, including a paretiqaul e snce thereof which is the same sequence found in Nature. "Kvl.3" (also known as KCNA3, HGNC ID: 6221) is udse herein as the potassium voltage-gated channel subfamily A member 3 having a sequence, encode tdhe by KCNA3 in humans and several other mammals wahsere by the Kcna3 gene in murines, exemplarily shown Un iniProt accession number P22001for humans or P16 fo3r90 mouse or counterparts, i.e. the corresponding g (eonrtehsologs) from other mammals or vertebratesh.o Olortgs can be searched e.g. in the Gene database held by thoen Naal t Cienter for Biotechnology Information, Nation Laiblrary of Medicine, National Institutes of Health, USA. The term “inhibitor” of Kvl.3 is used herein aso am cpound that inhibits, i.e. reduces Kvl.3 funct bioyn at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 8805%, , 90%, 95% or 100%. The term inhibitor is usedinterchangeably with “antagonist”. "Binding selectivity" refers to the measurement h o wf selectively a molecule interacts with differe tanrtgets,preferably quantified by the ratio of absorbancelue vsa obtained in phage-ELISA binding assays thatn qtifuy the amount of binding of monoclonal phage particlespl daiysing a specific Kv1.3 inhibitor protein. Sucha pghe ELISA assays were carried out to test the binding of p shaaidge particles to chimeric KcsA-Kv1.3 T+F, KcsAv-1K.2 and T+F KcsA-Kv1.3 T+F immobilized target proteins. (KcsAtan sds for “K channel of streptomyces A” as expladine hereinbelow.) Thus, the indicated binding seletcytivi alues refer to phage binding-related absorba rantcioes tested on two different chimeric target proteins, such asA K-cKsv1.3 (T+F) / KcsA-Kv1.2 (T+F) or KcsA-Kv1.3 (T+FK) / csA- Kv1.1 (T+F). A higher ratio predicts greater seilveictyt, meaning the molecule preferentially binds K tov1.3 over Kv1.2 or Kv1.1. Binding selectivity is useful forss aessing the specificity of interactions in biochiceaml assays, ensuring that a molecule demonstrates targetedvit ayc,ti which is essential for effective and safera thpeeutic applications. “Inhibition selectivity” refers to a measurement h oofw selectively an inhibitor inhibits differentrg taets, preferably quantified by a parameter of activinty; a i particular embodiment as used herein, „sele”c otivr „selectivity” refers to the ratio of IC50 values for Kv1.1 to I aCn50 values for Kv1.3 or IC50 value for Kv1.2 to I aCn50 value for Kv1.3. IC50 values may be used as a measure obfit inohri potency of an inhibitor compound. An IC50u veal is a measure of the concentration of an inhibitor reeqdui tro achieve half of that compound’s maximal inithioibn of ion channel activity in a given assay, herein a patlachm-pc assay measuring current flowing through thsete tde type ofchannel protein. A compound which has a lower IC at5 a0 particular ion channel than a reference comndpo cuan beconsidered to be a more potent inhibitor, than re thfe rence compound.“Panning / biopanning" in phage display technology a i ms ethod for isolating peptides or proteins wiitghh h affinity to a target. This involves incubating aa pghe library with an immobilized target, washing w ofefakly-binding phages, and collecting strongly-bound phages. T ahreese then amplified for further selection. Biopanngni may repeatthis process under stricter conditions or againuslt ip mle targets to enhance specificity and effeecntievss.The terms "non-naturally occurring" or "engineereadre" used interchangeably and indicate the invoelvnetm of the hand of man. The terms, when referring to nicuc alecid molecules or polypeptides mean that thele nicuc acid molecule or the polypeptide is at least substalynti farele from at least one other component with whh tihcey are naturally associated in nature and as found inr nea. t Tuhus, a variant of a wild type as used hersei nne icessarily non- naturally occurring. The term “conjugate” relates to a compound formyed ch bemically joining two or more different substaens.cpreferably, chemical joining means covalent join.i Inng particular, as used herein a protein or poplytipde conjugate(or conjugated protein or polypeptide) comprisees K thv1.3 potassium channel inhibitory polypeptide th oef invention and a conjugating moiety which is covalently atteadch to the other part of the molecule making itn aju cgoate; whereasthe conjugating moiety comprises a prosthetic gr tou pprovide an additional function to the Kv1.3a psostium channelinhibitor compound of the invention. The prosthe gtricoup may be any moiety, e.g. a peptide or a neopnti-dpe type, toprovide this additional function, Typically the psrtohetic group is a non-peptide part of the conjiunga mt oiety.The conjugate may comprise a linker moiety link tihneg prosthetic group to the polypeptide as defi ine tdheinvention. The main function of the linker moiesty to i provide a covalent connection between thep peopltyide and the prosthetic group. The linker moiety may be a spa mcoeirety which has the function to provide a distean bcetween the polypeptide of the invention and the prostheticu gpro so that their functions may not impair eachr o.the The term "fusion protein" as used herein refer as p torotein that includes polypeptide componentsv deedr firom more than one parental polypeptide. In particu ala pra,rental polypeptide may be a protein moiety whh micay exist in itself or as a protein domain or as a miniprote Inin a.n embodiment a parental polypeptide componfen intte orest islinked to a single polypeptide chain with anothearre pntal polypeptide used as a fusion partner. Tahre n ptalpolypeptides may be protein domains including pbolyss oi ne or more miniprotein(s), and may have th oewirn functions. Alternatively, the fusion protein comspinrig or formed by multiple polypeptides may form co ammon functional unit. A fusion protein may be prepareyd r becombinant methods using a nucleic acid codhineg w tholefusion protein. Alternatively, fusion proteins m baey prepared by linking by an amide bond the palre pnotlaypeptidesin vitro, e.g. chemically or enzymatically. A "theranostic" pair as used herein is a combinieadgn dostic compound and a therapeutic compoundh feor t therapy of a condition diagnosed by using the doiasgticn compound. A “composition” is understood herein as a non-naaltlyur occurring composition of matter which comprsis aetleast one biologically active substance as defi hne rdein in an effective amount. Compositions mayo a closmprisefurther biologically active substances or a mixtuofre biologically active substances. Furthermore, c thompositions may comprise biologically acceptable carriers, fuolramtion agents, excipients etc. which are well kno inw the art. A “pharmaceutical composition” of the invention a is composition of matter which comprises at leaset on compound of the invention comprising an active atg aennd at least one further substance. Preferabely co thmpound ofthe invention is present in an effective amountm. Cpo sitions may also comprise further biologicalclytiv ae substancesuseful e.g. in a combination therapy. Furthermo thre, compositions may comprise biologically accelpeta cbarriers,formulation agents, excipients etc. which may boew kn in the art.The term “effective amount” qualifies the amount a o cfompound required to exert the effect of theive ac atgent in a composition. A “therapeutically effective amnot”u is sufficient to reduce or relieve or prevenotr ( preventworsening of) one or more of the symptoms or chtaera isctic parameters of a condition, e.g. a disor odre drisease, orwhich normalizes physiological responses. In one aspect, a therapeutically effective amoufnt a o compound of the invention, or a pharmaceutical composition, is an amount which restores a measleur pahbysiological parameter to substantially the e sa vmalue (preferably to within 30%, more preferably to wnith 2i0%, and still more preferably to within 10% h oef t value) of the parameter in an individual without the condnit oior pathology in question. A “subject” as used herein is an individual of annim aal species, preferably a vertebrate, more parebfleyr a mammalian or avian species, in particular a mamamna slipecies, highly preferably the individual isr aim pate, a hominid or a human. A “patient” is a subject who o irs intended to be under medical or veterinariasne orvbation, supervision, diagnosis or treatment. A “treatment” of a subject refers to any procescsti,o an, therapy, or the like, wherein the subject pa otrient isunder aid, in particular medical or veterinariadn w aiith the object of improving the subject’s ori peant ’s condition,either directly or indirectly. Improving the subtj’esc condition may include restoring or maintainin ogrmal function of an organ or tissue, preferably at least paretlsyto rring or maintaining health (medical or veterriianna treatment). Treatment typically refers to the administration a onf effective amount of a compound or compositioensc dribedherein. In a broader sense treatment includes m boetdhical or veterinarian treatment and preventiorn p (ro phylaxis)i.e. prevention of the onset of a disease as w ine all, more limited sense prevention is not covered. The “level” of Kv1.3 channel protein in this conte isx to be understood as the measured amount o.f3 Kv1 channel proteins detectable by any method in a l sea,m epither on the surface of a cell, i.e. embed idne tdhe cell membrane or inside the cell. The measured amou an qtu isantitative (i.e. quantified) result of a meraesmuent. The term “amount” is to be understood broadly to includee enxstive quantities like number of molecules, macstsiv,i aty or the corresponding intensive quantities like concenotrnat oir specific activity etc. The skilled personl w uinlderstand that the level of the Kv1.3 channel protein in a sam dpelepends on the measurement method. For example, if a measurement method comprisesin bgin odf a reporter molecule to the Kv1.3 channelte pirno and this binding can occur within the cell, thee lle ivs understood as including the amount or conracetionnt of theKv1.3 channel protein within the cell and alsoh ine t cell membrane. Examples for such measuremenhto mde intcludeimmunohistochemical methods wherein fixation isli aepdp and thereby the cell membrane is impairede oars murement with a fluorescent dye or substrate which can preanteet he cell membrane (e.g. in certain flow cytotrmy e methods). For example, if the measurement method comprisnedsin bgi of a reporter molecule to the Kv1.3 channroetle pin in the cell membrane, then the level is underst aoso ad result of the measurement of cell surface3 K cvh1a.nnel protein.This is the case for example when an inhibitor coumnpd of the invention is used for measurement aind s b to theKv1.3 channel protein active site from the extraluclaerl space or when an antibody or other non-memneb praenetrablebinding molecule is used as a reporter moleculge. ( aes. a primary antibody) and the cell is intact h saot the bindingmolecule cannot contact Kv1.3 channel moleculeisde in tshe cell. In a preferred narrower meaning the level is theas muered amount (or concentration) of Kv1.3 channroetle pinson the surface of the cell as embedded in the m ce mll brane. In particular, the level of Kv1.3 chan pnreoltein ismeasured on particular cells (briefly: surface exspsiron) that mediate the said disease, or on trhfaec seu of a cell involved in disease progression. Such cells are e fxoarmple but not limited to: T lymphocytes, B lymopchytes, macrophages, adipocytes, smooth muscle cells arniodu vsa tumor cells. “Protein expression” in the broadest sense is usntodoedr herein to cover both “gene expression” wh reicfhers to the processes that convert the information oAf D gNenes into functional copies of mRNA in livingll cse and “protein production”, i.e. the biological method of genenragti an amount of a specific protein in a cell. I pnre aferred narrower sense protein expression refers to the productfio pnro oteins by cells, including synthesis and, onpatiloly, modification thereof, in particular their synthesis by transolnati from mRNA and, optionally, post-translationald mifoications. “Protein expression” is the regulated way in an lgivi organism in which the level of a given protesin re iached in a cell or tissue. An ”elevated level” is understood herein as a le wvheilch is higher than a reference level, preferab nlyormallevel. In a particular embodiment in any of thee dais es or disorders the level of Kv1.3 is elevante cdom i parison witha reference level, preferably a normal level. An elevated level of a Kv1.3 channel protein isen of dtue to an increase protein expression in comsopnar wiith a reference level, i.e. “overexpression”. A “reference level” is a level which is consider aesd a basis of comparison. In a particular meanhieng re tference level is a baseline level, wherein a level highne cro imparison with the baseline level indicateslt aenra ation in a sampleor in the source of a sample (e.g. a subject), a e d.gis.ease or disorder or the tendency of a su tbhjec retfor.A “normal level”, including a “normal range” of levls, is a reference level measured in connectiothn a wicohort or a population of subjects is a range v oefl lse typical of, i.e. measured in healthy subje Icnts p.articular thenormal level is a level measured by a method preodvi hderein. In a preferred sense the “normal le ivse al” normalrange which is relatively narrow or a single value. A normal level, in an embodiment, may be obtaineyd a b measurement parallel with the measurement of abiological sample from a subject, wherein the nolr lmevael is measured in a biological sample frome a lt hhy subject.A normal level, in another embodiment, may be onbetdai by measuring the level of Kv1.3 potassium cheal nn proteins in a multiplicity of healthy reference sjeucbts, e.g. by the method according to the invenn,t aiond statistically analyzing the multiplicity of results measured, wrehbey determining a range in which the level of K3v1 p.otassium channel proteins can be considered, which a seunfftic ciertainty, typical of a healthy person. Ino aa bdrer sense normal range and normal level are used interchangeably. “Comparing” two levels is understood herein tou indcel a comparison to establish which is higherw ore lro, or establishing a difference or establishing a raftio th oe levels, or values derived from the levelst,io onpally completed with other mathematical procedures (calculation t)h aes measurement method requires. In an embodi cmoemnptaring comprises subtracting two levels, e.g. subtract winog normalized or baseline-corrected level. In amnbo edimentcomparing comprises a mathematical procedure, tr ea.gns. formation carried out on both levels, e.g.cu clal tinglogarithm, or other function. In an embodiment coamrinpg comprises making statistics and calculatirnrogr es and / or means or averages which is / are considered, ansds / oerss ament of statistics assessment of statisitgicnaiflic sance. The term “comprising” or “including” given compontesn or elements or species or moieties or methopds s iste understood herein as having a non-exhaustive mgea annind as containing said elements (e.g. feature sspe ocries ormoieties) and optionally further elements as w i.el .l, comprising does not exclude the presencer othfe fur componentsor elements or species or moieties or method s Ttehpes. terms comprising and including are interchanbglee herein. The expression “consisting essentially of” or "cormisipng substantially" is to be understood as cotins gis ofmandatory components or elements or species orti mesoi oer method steps listed in a list e.g. in aim cla whereas allowing to contain additionally other componenrts e olements or species or moieties or method stehpicsh w do notmaterially affect the essential characteristics th oef use, method, composition or other subject mr.a Ittte is to beunderstood that “comprises” or “comprising” or “liundcing” can be replaced herein by “consisting etsiasellyn of” or "comprising substantially" if so, required witho audtdition of new matter. The term comprising can be limited to consistinsge enstially of or consisting of without addition oefw n matter. The indefinite articles “a” and “an” may be consetdru as referring to either singular or plural, e m.gu.ltiple elements may be present. ABBREVIATIONS 3D Three dimensional AD autoimmune disease AgTX Agitoxin potassium channel toxin fro Lmeiurus quinquestriatus hebraeus ALS amyotrophic lateral sclerosis APC Antigen Presenting Cells (macrophages, B cellsd,r diteicn cells) AUC Area Under the Curve BLAST Basic Local Alignment Search Tool. BSA bovine serum albumin CHO Chinese Hamster Ovarian Cmax Maximum serum concentration COPD chronic obstructive pulmonary disease DDM N-Dodecyl-β-D-maltoside DTH delayed-type hypersensitivityHsTX1, ShK EAE experimental autoimmune encephalomyelitis ECS extracellular solution ELISA Enzyme-linked Immunosorbent Assay FASTA Fast All (a text-based format for represent einitgher nucleotides or amino acid sequences) FBS fetal bovine serum Fmoc fluorenylmethoxycarbonyl protecting group HA hyaluronan ISEP Individual Sequence Enrichment Pattern ISEP Individual Sequence Enrichment Patter KCNA3 potassium voltage-gated channel subfamily A meerm 3b KcsA K channel of streptomyces A KePharmacokinetic elimination rate constant KTX1 Kaliotoxin-1, a neurotoxin derived from the spcoiorn Androctonus mauretanicus Kv1.x any member of the “Shaker-related subfamilfy v” o ltage-gated potassium channels (Kv1.1-Kv1.8)LC / MS liquid chromatography–mass spectrometry MeKTX13-2 Potassium channel toxin derived from tchoerp sion Mesobuthus eupeus. MP microparticle MW molecular weight NGS Next Generation Sequencing PAM poly(acrylamide) PASI Psoriasis Area Severity Index PBMC peripheral blood mononuclear cell PBS phosphate-buffered saline PCL polycaprolactonePEG poly(ethylene-glycol) PK pharmacokinetic PLA polylactic acid PLGA poly(dl-lactide-co-glycolidePLLGA poly(l-lactide-co-glycolide PNK polynucleotide kinase PVP poly(vinylpyrrolidone RCF remaining current fraction RT room temperature Tem effector memory T cell Tmax time to peak serum concentration BRIEF DESCRIPTION OF THE FIGURES Figure 1. The subunit structure of the KcsA and KcsA-Kv1 c.hximera compared with the human Kv1.x channels. Structural characteristics of the humva1n.x K channel pore domains (in dark grey), and t shpeeircific regions interacting with pore-blocking peptide toxins ariegh hlighted with black (turret region) and greyt (efirl region). Forthe human Kv1.x channel, the 6 transmembrane hse alicre denoted from S1 to S6 (Figure 1.A). For thilde t wype KcsA and the chimeric KcsA-Kv1.x proteins, thea 2n tsrmembrane helices are denoted as TM1 and TM2h. t Bheot KcsA and the T+F chimeras harbor an N-terminal 6isx-t Hag (Figure 1.B). The transferred turret reg iiso hnighlighted in thick black, and the filter region is highlighdte in thick grey. For clarity, only 2 opposite subitusn of the tetrameric channels are shown for both structures. Figure 2. Sequence alignment of the wild type (WT) KcsA pirnot aend the chimeric Kv1.x T+F expression constructs. Amino acids of the turret region argeh hligihted in black, and the filter region is higghhlited in grey. The sequence of WT KcsA is shown in SEQ ID NO:86, tehqeu sence of KcsA-Kv1.3 is shown in SEQ ID NO: 87e, thsequence of KcsA-Kv1.1 is shown in SEQ ID NO: 8n8d, a the sequence of KcsA-Kv1.2 is shown in SEQ ID: N 89O.Figure 3: Dose-response relationship for lead compou onnd Ksv1.3. The dose-response curve was generated by plotting the remaining current fraction (RCF / I =₀) I as a function of toxin concentration, where I a I₀n rdepresent the peak currents in the presence and absence otofx tihn, respectively. The data were fitted usinquga etion 1 RCF = Kdn / (Kdⁿ + [Tx]ⁿ), (1) where [Tx] is the toxin concentration, Kd / IC50h ise t dissociation constant, and n is the Hill coeieffnict. Error bars represent the standard error of the meanM (S.).,E w.ith n = 3–6. Figure 4. Serum stability of newly identified compounds a Dnadlazatide. Figure 5. T cell specific (A) CD25 and (B) CD40 activationa mrker expression in CD+4 Effector memory T cells. All Kv1.3 channel targeting peptides werepl aiepd in 50 nM concentration before CD3 (OKT3) sutilmus. Inhibition was compared to CD3 stimulus controlh woiutt peptide treatment. Statistical Analysis: Onaey-W ANOVA with Dunnett’s post-hoc test. Error bars repres meenatn ± SD **** p < 0.0001. Figure 6. T cell specific (A) CD25 and (B) CD40 activationa mrker expression in CD+4 Effector memory T cells. Kv1.3 channel targeting SEQ ID NO: 22 peept widas applied in 0.16-100 nM concentration befoDre3 C (OKT3) stimulus. Inhibition was compared to CD3 stimuluosnt crol without peptide treatment. Statistical Ansaisly: One-Way ANOVA with Dunnett’s post-hoc test. Error bars respernt mean ± SD ***p<0.001; **** p < 0.0001. Figure 7. IFN-γ secretion of CD4+ effector memory T cells. Both1 K.3v channel targeting peptides wereapplied at either50nM concentration for 30 minu btes fore CD3 (OKT3) stimulus. Inhibition was compar teod CD3stimulus control without peptide treatment. Datea i allurstrated as mean ± SD of n=4 parallel measuernetsm. Statistical Analysis: One-Way ANOVA with Dunnett’s post-hoct t.e nss p>0.05; *** p < 0.001; **** p < 0.0001. Figure 8. Normalized IFNγ- secretion of CD4+ effector memory T cells. Both1 K.3v channel targeting peptides were applied at 25 nM concentration f hooru 4rs before removal of the inhibitors. After 4s da reysting, T cells were activated by CD3 (OKT3) stimulus. Inhibitionas w compared to CD3 stimulus control without pep ttriedaetment. Data are illustrated as mean ± SD of n=4 parallelas murements. Statistical Analysis: One-Way ANOVAth wi Dunnett’s post-hoc test. ns p>0.05; *** p < 0.00 **1*;* p < 0.0001. Figure 9. Semi-logarithmic representation of the mean pla lsemveals of the test items (n=4). Dose: 1 mg / kg s.c. for each peptide. Plasma concentrations folarz Daatide and its metabolite were taken from Tarc Eh.a J,. et al. [Tarcha, E. J e.t al., 2012]. Figure 10. Effect of SEQ ID NO: 22 treatment on oxazoloneu icnedd ear inflammation in rats. Figure 11. The putative fold of the miniproteins of the invtieon. As an example, the fold of SEQ ID NO: 22 is shown. Figure 12. Cysteine disulfide bonds in the putative fold th oef miniproteins of the invention. Disulfide bondscan form in the secondary structure of the miniepirnot SEQ ID NO: 29 as shown in Figure 12.A. The ceonnssus sequence contains cysteines in positions 8, 142,81,83,3, and 35 are specifically indicated in thieew v on Figure 12.B. DETAILED DESCRIPTION OF THE INVENTION Kv1.3 appears to be a valid drug target for tregat ainutoimmune and inflammatory diseases. Although numerous Kv1.3 channel inhibitors have been deesdc,rib among them natural toxin-based polypeptides andminiproteins, there is still a need for highly scetilvee druggable compounds. However, selective tainrge of the Kv1.3potassium channel is challenging due to high sirmityila to other voltage gated potassium channelst,ic pualarrly Kv1.1 and 1.2 channels. Polypeptides, especially mineipinrost with determined tertiary structure that iss siteivne to mutations can be particularly suitable for designing highin aitfyf and selective drug candidate compounds. Ph daisgpelay is an effective and economical tool for optimization ofly ppeptides based on their target binding affin pirtoyvided that the target protein can be immobilized on solid surf saoce that it preserves its original structure. Howre, v imemobilizing the natively membrane-embedded Kv1.x channelsis in m thanner so far was not possible. To circumveinst p trhoblem, a group of researchers [Legros C. et al., 2000p]o psreod that a chimeric potassium channel proteined ba osn the K channel of streptomyces A (KcsA), in which aminoid a rcesidues of the turret region are replaced w coitrhresponding amino acids of the Kv1.x channels (see Figure 1 F aingdure 2), is suitable for solid surface immobailtiizon anddetecting the binding of Kv1.x channel blockers th toe binding site in this region. Using this apprho,a ic.e. phagebinding to KcsA-Kv1.3 turret (KcsA-Kv1.3 T-only)t treameric chimera protein, some groups identifiewd n Kev1.3 blockers, such as mokatoxin-1 (Moka1) [Takacs Z a.l, e 2t009]. However, several studies have showtn in tha dditionto the turret region, part of the filter region a ils o responsible for selective ligand binding,e thfoerre the validity ofthe T-only chimeras in predicting relative bindi anfgfinities of potential ligand molecules might bimei lted [Tyagi A. et al., 2022; Visan et al., 2004]. Attempts to rmecboinantly produce active chimeras harboring boeth tu thrret and thefilter region (denoted as T+F) of human Kv1.x chealnsn in a heterologous expression system were uens sufcucl dueto poor expression and inaccurate assembly of moenrsom resulting in a defective tetramer [Legros C a.l. e,t 2000; Sharonov G.V. et al, 2021]. However, the inventors of the present inventionce susscfully elaborated a process for recombinantu pcrtoiodn of KcsA-Kv1.1, KcsA-Kv1.2 and KcsA-Kv1.3 T+F chimaesr (Figure 1 and Figure 2) that preserved theirve act conformation when immobilized on solid surface [kSézre P. et al., 2024]. By testing numerous knownas psoitum channel blocking toxins (Vm24 toxin, Hongotoxin- K1a,liotoxin-1, Maurotoxin, Stichodactyla toxin) inha pge- displayed form, they proved that the binding ofs tehe phage-displayed toxins to the three types oAf K-Kcvs1.x T+F chimeras are predictive for the channel blocking th oen three respective human Kv1.x channels. Thdeic ptrioens by binding to KcsA-Kv1.x T+F chimeras was much morens ciostent with native Kv1.x channel blocking poteensc,i than binding to KcsA-Kv1.x T only chimeras. Thus, thend biing of phages to KcsA-Kv1.x T+F chimeras cans beed u either for selecting strongly binding miniprotein sequesnc bey biopanning of phage-displayed libraries and fo / orr assessing relative binding affinity and selectivity of monocnlal phages to human Kv1.3, Kv1.2 and Kv1.1 poutamss cihannels. Traditional biopanning methods (such as industarynd satrd phage display) are slow and biased, lim toite hdand- picked miniprotein structures and a fraction ofd bining candidates due to physical library constra.i Hntoswever, the integration of Next Generation Sequencing (NGS)m dartaically enhances this proce [sKsappelmann-Fenzl M.202].1NGS enables rapid, comprehensive analysis of i vbarsatri les, improving hit quality and quantity. Bys aes sing relativeenrichment across millions of sequence variants on o-n / off-targets, NGS reveals not only strong binsd beurt also provides a preliminary selectivity assessment. g Us thine ISEP (Individual Sequence Enrichment Pattearnna)lysis,library bias can be overcome, and counter-screaens be c performed. The inventors of present invention decided to conmeb thi e newly produced KcsA-Kv1.x T+F chimera target proteins, the phage display technology for gennegra ntiew natural toxin derived miniprotein librari aensd the NGS- assisted analysis for seeking for new high affin aintyd highly selective Kv1.3 blocking drug candid matieniproteincompounds. The process of identification and chtear iazcation of the compounds of present invention c baesummarized as follows: 1. First, KcsA-Kv1.1, KcsA-Kv1.2 and KcsA-Kv1.3 T+F i cmhera proteins were produced by a recombinant production method. 2. Combinatorial phage-display libraries of approxiemlyat 2.3-million-member size were designed and cerdeat based on sequences of known nonselective or moedlyer saetlective Kv1.3 inhibitors. The libraries were designed by combining multiple segments of known1. K3v inhibitors, such as MeKTX13-2, AgTX2, AgTX3 and, KTX1. 3. The created phage-display libraries were screeyne bdio bpanning on solid surface-immobilized chime Krivc1.3 protein using also an NGS-based negative sele (cit.ieo.n exclusion of) sequences enriching on chim Kevri1c.1 and Kv1.2 proteins. 4. From screening of the libraries in several scregen cianmpaigns phage-displayed polypeptide compounitdhs w high phage enrichment rate on Kv1.3 chimeric prnoste ais compared to chimeric Kv1.1 and Kv1.2 proteins were selected and tested in a phage-ELISA bindsinsgay a to confirm their high affinity and selectiv.ity 5. Taking some lead sequences with high affinity teo K thv1.3 chimeras and selectivity over Kv1.1 and . K2v1 chimeras, further optimization was carried outi btey- sdirected mutational changes in various segm oefn tthsese leads to further optimize their affinity and seilveictyt, which were then assessed by the phage-EL bIiSnAding assays on the chimeric Kv1.3, Kv1.2 and Kv1.1 retocresp. This process yielded the 47 new polypeptide sequences presented in Table 1 and Table 2. 6. Each of the sequences resulted in an unforeseerena isnec of binding selectivity both against Kv1.1 aKnvd1.2 chimeras. In particular, it could be concluded thaet amino acids N-terminal to cysteine in gen peoraslition 8 appear to be less important for binding selecti tvhitayn other parts of the molecule. In particular, the C-terminal segment, e.g. them seengt C-terminal to cysteine at position 18 showed a higher conservativity with residues 19 to 23 be Linygs-Glu-Ala-Gly-Met (the latter being replaceablte le aast by norleucine Nle). Residues in positions 24 and al 2lo5wed a limited flexibility between Arg and Th inr position 24 and the phenyl comprising amino acifd Tsy or or Phe in position 25. While positions 26 and 27 proved to be conserveyds ( 2L7 being necessary for active site blockinge), thfurther contribution to selectivity appeared to a bsesignable to position 34 as well as the small seengtm C- terminal to Cys in position 35 with a limited vatrioian options including a deletion of terminal segnmt aemino acids in positions 37 and 38. These observations are supported in Table 2 ancdlu cdoend in formula (1) and in paragraphs 1 and 2 in the Brief Description.7. To verify the high efficacy and selectivity of th se lected compounds predicted by the phage-ELISdAin bgintest, a set of 17 new compounds were recombina pnrotldyuced in free miniprotein form, which repres aelnlt the preferred amino acids at least once in ther deinfft positions of the sequences in Table 1 anlde T 2a (bSEQ IDs up to NO: 38 in Table 3). Potassium channeclk bilnog potencies of these miniproteins were tesyte wdh bole cell patch-clamp assay on native Kv1.3, Kv1.2 anvd1. K1 channels.8. Furthermore, taking SEQ ID NO: 22 as an exempleaaryd l sequence, mutations or other chemical chanegres wcarried out to see if the changes could be tolder watieth preserving high potency and selectivityh oifs t lead compound. The changes included some single pointatt miouns, including deletion of the C terminal reuseid and modifications that required synthesis, e.g.la rceinpg C terminal carboxyl group with carboxamid oer, replacing a proteinogenic amino acid with an anoaulosg non-proteinogenic amino acid, such as repla tchieng oxidation-prone methionine with norleucine. Thec pha-ctlamp experiments with the selected compounds shown in Table 3 and Table 4 indicated high pote anncdy surprisingly high selectivity of the compou.nd Asll the new compounds in Table 4 had considerably p hoigthency (IC50 <100 nM), their majority had very hig potency (IC50<10 nM) and eight of them had extreym heigl h potency with subnanomolar IC50 value for inhibiting Kv1.3 potassium channels. What is mo arell, of them but three showed more than 2000-fold selectivity, and the remaining three compounds m haodre than 100-fold selectivity. These good pote anncdy selectivity values are particularly surprising ahsey t far exceed such values of the recombinantlydu pcreod MeKTx13-2 toxin, which had Kv1.3 IC50 >100 nM anedle sctivity <10-fold. MeKTx13-2 was one of the starting molecules of library building and is onfe th oe closest analogs of many of the hit compoun fodrs, example SEQ ID NO: 2. Thus, the patch-clamp experiments, reporting oenc stievlity based on blocking activities of the ser oiefs miniproteins, unforeseen based on phage display to le thde result of a high, i.e. more than 100-foeldlec stivity in a subset of sequences, and, even more surpr thisein mgore than 1000-fold selectivity in the vastjo mriaty of this subset and some even higher than 10,000 o,0r005-0fold. These observations are reflected in fuolarm (2) and the amino acid definition in paragraphs 3 a,n rdes 4pectively. Notably, Leu 15 proved to be ano imrtapnt position for the particularly preferred subset, w aesll as the selection of phenyl side chain comnpgris Pihe and Tyr in position 36, wherein Phe appeared to bee prre df (see paragraph 5), Gly and Pro (or a del)e itnionposition 37 with Pro as less preferred, and Arg a (o dreletion) as particularly preferred in positi 3o8n. The presence of a basic straight chain amino acid,a irntic pular Lys or Arg, if protein-forming amino acsid are applied, remained to be highly important in posnit 3io4. As a minor surprise, Tyr or Phe proved to be prefder in position 25, Ser in positions 17, and Glnd an Lys, in particular Gln (over Glu) over Lys in poiosint 16 from the point of view of selectivity. All these observations are supported in Tablesd 34 an and concluded in formulae and definitions in paragraphs 3 to 4. In a subset of sequences thibeito inrhy effect was particularly strong, and an IC v5a0lue lower than 1 nM was achieved (see Table 5 and folarem iun paragraph 7). For multiple lead compounds we also determined the exact IC50 values on Kv1.3u (rFeig 3). 9. A representative set of 6 compounds were seleclsteod fo ar testing their stability in human serum. Athlel tested compounds proved to be sufficiently stable in hum saenrum, indicating druggability of these polypeeptid compounds from this point of view (see Figure 4). 10. Further in vitro investigations were performed with a selected co semtpounds to determine whether they have the desired inhibitory effect on activation of t thaergeted T cell population, which is the expectpeedc sific immunological based on their selective blocking K ov1f .3 channels (see Figures 5 and 6). 11. A pharmacokinetic (PK) study by subcutaneous adsmtriantiion and blood serum sampling pre-dose and at different post-dose timepoints was performed ins. ra Tthe results indicated that all the tested comndpsou absorbed rapidly from the injection site and show ae fdavorable in vivo pharmacokinetic profile thatn c be expected for a miniprotein of this size (Figure 9). 12. An in silico immunogenicity assessment using netMHCIIpan-4.e3di pcrted that the lead Kv1.3 inhibitor peptides are non-immunogenic in humans. This csotnstr waith several competitor peptides, which showe adk (si544, OsK1[H34A], Moka1, AgTx3) or strong (MeKT3x21) predicted immunogenicity. Predictions were based on %RankEL scores across a broad range of c HlaLsAs II alleles (Table 7). 13. The lead compound SEQ ID NO: 22 was tested als ao m inodel of contact dermatitis in rats which indeicda itts effectiveness to inhibit a disease-relevant inflaamtomry process in vivo (Figure 10.) Further details of this process and its results p areresented in the Examples. Therapeutic methods and administration In the therapeutic method of the invention thev aitcyti of Kv1.3 channel is inhibited in the blood,m lyphaticsystem, and other biological tissues, wherein theeth mod comprises administering Kv1.3 potassium cehla inn hibitorcompound to a subject in need thereof. In a particular embodiment the subject is an an,im praelferably a vertebrate, in particular a mammal. Examples of such animals thus comprises mammahls a ssuc rodents, dogs, cats, farm animals, e.g.o livceks otr pet animals. In another embodiment the subject criosmesp birds, in particular poultry. The invention may be utilized in any therapy wh iet irse desired to treat, reduce or alleviate sympstom f Kvl.3- mediated diseases such as any disease listed B inrie thfe Description of the Invention. It has long been known that+K channels are important regulators of cell excliittayb ais they contribute to maintaining the resting membrane potential and o todu mlating neurotransmitter relea [sReudy B, 1988], which supports their use in a number of neurologicala dsieses. In non-excitable cells, however,+K channels regulate cell differentiation and proralifteion, apoptosis, and several other physiological functions. The alteornati of K+channel activity and expression can cause profound pathophysiological events in many different ceplle tys [Choi BH et al.201]0. Thus, pharmacological agents that inhibit K+channels can lead to beneficial therapeutic oorw uanrtd side effects. In particular embodiments, the disease is sele fcrtoemd the group consisting of immunological disea, sesinflammatory diseases including chronic inflammayto driseases or T-cell-mediated inflammatory disosr,derautoimmune diseases, cancers, neuroinflammator nye our ological disorders, conditions associated w witehightmanagement, metabolic disorders and smooth mursoclliefe prative disorders. Typically, the level of Kv1.3 in certain cells isle evated in these diseases. Usually, elevatione o Kf tvh1.3 level is due to overexpression of Kv1.3 in the cellsc aisastoed with the given disease and consequentlnyc arnea ised amount and activity of Kv1.3 in these cells. In a preferred embodiment the disease i ism amnunological disorder. In the classic paper of Wulff et al., it has beeisncl dosed that Kv1.3 is specifically overexpressned ef ifector memory T (TEM) cells (e.g. in activated CCR−7 cells) whereas (CCR+7 naïve) central memory TC(TM) cells preferentially express the KCa3.1 chan [nWelulff H. et al. 2003]. Wulff H et al. in a later review paper advisedat th as KV1.3 is overexpressed in several cell types, incnlgud Ti and B cells, macrophages, microglia, osteotsc,la pslatelets, indicating that KV1.3 contributes to several K-channel related diessea (cshannelopathies) in various tissues. Wulff et al. also suggested that in activated effector meym To crells, KV1.3 constitutes a promising target for the treattm oefn autoimmune diseases and that in fact seveVra1l.3 K blockers are in preclinical development forh su dciseases like multiple sclerosis [Wulff H. et al. 2009]. It has been observed that the Kv1.3 expressiolenct siveely increases from^~^300 to^~^1500 / cell in TEMupon activation which makes their activation anrodli pferation sensitive to Kv1.3 inhibition. Unfortunately, overactiveETMcells are also autoreactive and induce tissueg deam ina many autoimmune diseases. Taken the above results into accounrt a thcteiviation and proliferation can be preferenytia slul ppressed by selective Kv1.3 blockers without affecting naïved a TnCMcells. TEMcells with high Kv1.3 expression can be found in areas of inflammation related to autoimmune disse,as lineking Kv1.3 activity to autoimmune processes, and inhibition of Kv1.3 was found to be effective in p asoriasis model in mic [eKundu-Raychaudhuri S. et al. 20]14 Thus, selective Kv1.3 inhibitors of the presente in tvion are good candidates for selec itmivemunosuppressionin immunological disorders, and in particular where thine immunological disorder is an inflammatory ddiseorr or an autoimmune disorde [rBeeton C. et al. 200][6Varga Z. et al. 202]1. Treatment option of immunological disease viainhibiting Kv1.3 is reviewed in a recent paper bayv Narro-Pérez et al. It is concluded that Kv1.3-bda trse atments willensure therapies while minimizing undesired sidfe c etsf [Navarro-Pérez, M. et al. 20]2.4High expression levels of Kv1.3 in intestinal muaco hsave been correlated with increased levels o-f pro inflammatory cytokines and disease activity ine pnattsi with ulcerative coliti [sHansen L.K.201]4. This finding points to potential therapeutic utility of Kv1.3 inhibitsor and makes Kv1.3 a potential diagnostic marker a fsosressing inflammatory activity in inflammatory bowel diseass.e Moreover, suppressing Kv1.3 ion channel activ witityh an inhibitor ameliorated inflammation in a humanizedou mse model of ulcerative colitis. Kv1.3 also regulates neutrophil recruitment andg pohcaytic activity during inflammation. Thus,VK1.3 plays a role in inflammation not only via T lymphocytes,t b aulso via affecting neutrophil trafficking and pghoacytosis [Immler R. et al., 2022]. This also confirms thee u osf the selective inhibitor compounds of the intvioenn in the treatment of inflammatory disorders. The present invention is also useful in in thet tmreeant or prevention o cfancers in which Kv1.3 is involved. This is often the case, as altered expression o1f.3 K cvhannel has been found in several types ofr tsum anod cancer cells. [Comes N. et al. 201].3 Kv1.3 channels are involved in the switch to i pferoraltion of normally quiescent cells, and thus are involved in several proliferative drdiseor by the control of cell cycle in many differe cnetll types and in many different ways [Perez-Garcia M.T. et al.20.18] In general, Kv1.3 channels are involved in thev ac titoi n and / or proliferation of tumor cel [lBsielanska J. et al.,2009] and therefore their inhibition may be effective th ine treatment of cancers. Exemplary cancer tynpcelsud ie breast cancer, prostate cancer, and lymphoma, a ssu nchon-Hodgkin lymphoma (NHL). The inventive Kv1.3. channel inhibitor compoundse ar lso useful in the treatment of or prevention a of neuroinflammatory or neurological disorder. While in general it remains a challenge for theec etfifve treatment of neuroinflammatory disease,u idnicnlgmultiple sclerosis (MS), stroke, epilepsy, and Aelizmher’s and Parkinson’s disease, Kv1.3 channeoln is i cdered as atherapeutic target for treating neuroinflammatoirsyo drders, since it plays crucial role in subsets T o lyfmphocytes as well as microglial cells and other cells involvend n ieuroinflammation. As reviewed by [Wang X. 2020], among others the following diseases can be tdre bayte Kv1.3 inhibitor compounds of the invention: (1) Multiple scleros (i2s), ischemic stroke, wherein Kv1.3 plays importa ronltes in microglia as well as macrophage activation; (3)h Aelizmer’s disease, wherein neuroinflammation cassca mdeediated by activated microglial cells and T lymphocytest croibnute to the pathogenesis; and (4) Parkinsons’esa dsie, in which participation of Kv1.3 channel upregulation wasl iimcapted in several ways. The fact that Kv1.3 channels are involved in thteiv ac tion and / or proliferation of many types of cse,l ilncludingmicroglia [Khanna R. et al., 200]1 and differentiation of neuronal progenitor ce [lWlsang T. et al. 201]0 further confirms that Kv1.3 inhibitor compounds may be bfeicniael in the treatment of neuroinflammatory and neurodegenerative disorders such as Alzheimer'esas deis, multiple sclerosis (MS), Parkinson's disea nsde amyotrophic lateral sclerosis (ALS) (e.g. followi vnigral infections). The present Kv1.3 inhibitor compounds are alsou uls inef a series of diseases regard winegight management and metabolic syndrome or related disorders. Pvoes oitiutcomes in animal models with Kv1.3 blockersve ha been described in obesity, diabetes and metabolic deisrosr [dXu J. et al. 200]3 [Xu J. et al.200]4. It has been observed that Kv1.3 channel regulahtees ac ttivity of lymphocytes, macrophages, or adip toisse ueand its blockade reduces inflammatory cytokinee steiocnr and improves insulin sensitivity in animalisth w metabolicsyndrome and in genetically obese mice and bloc tkhaedre of normalized glycaemia, insulin resistan acdeip,osity, andlipid profile [Zayas-Arrabal J. et al.20]2.3 Thus, the invention is useful in the treatmentr oerv pention of conditions associated with weight mgaenmaent, such as inhibiting weight gain, promoting weighsts lo, reducing excess body weight, and related deisrsor ads well as metabolic syndrome, insulin resistance, glucosoele inratnce, pre-diabetes, increased fasting gluceovseels l, or type 2 diabetes. In an embodiment the inhibitor compound of the n intvioen is used in the treatment or prevention ofo stmho muscle proliferative and / or migration disordersh s aucs restenosis, particularly in patients follow vinagscular surgeries like angioplasty. Upregulation of Kv1.3 channels v ianscular smooth muscle cells (VSMCs) has beenic imatpeld in their switch to proliferation resulting in intim hayl perplasia and other unwanted vascu relamrodelling events. which constitute a common pathological lesion in occleus vivascular diseases. Therefore, Kv1.3 channeli itnohrsib may be effective in occlusive vascular diseases by supspinrges proliferation and migration of vascular smooth muscle cell [Cidad P. et al.2015] [Cheong A. et al.2011]. The skilled person will understand that the Kv1h.3an cnel inhibitors are useful in other conditionlsat reed tothose e.g. as listed in the appended claims ohre in B trief Description of the Invention.Diagnostic methods utilizing the compounds of the invention The compounds according to the invention can aels uos bed in diagnosis of Kv1.3 channel related deisse,a ins particular in diseases in which Kv1.3 channels esxspiron level is upregulated. A subject in need of such administration may beub aje sct diagnosed for example with T cell (prefeyra Tbelm cell) overactivation. The patient can be diagno bsyed known method for diagnosis of the diseaseso dsisecdl herein asdiseases the treatment or prevention of whichs is i pbole by the inhibitor compounds of the invention.T cell activation can be measured by methods susc mhe aasuring reduction of IL-2 production by T c.ells Alternatively, T cell activation can be measured a b dyiagnostic method according to the inventione,fe prrably via a binding of the Kv1.3 potassium channel inhibitorm cpoound to Kv1.3 potassium channel of the activa Tt-ecdells and thereby assessing increased activation of T cells. In particular, once the level of Kv1.3 channel perinost in Tem cells is increased, this is indicat oivfe the Tem cell-related diseas [eBeeton C. et al.200].6 In such conditions, a diagnostic assay can bete cmopnlated that quantifies the degree of the binding of a selective Kv1.3b inithoiry compound of the invention to assess thel le ovfe the counterpart Kv1.3 channel protein in the examineldl p copulation. In an alternative embodiment of this method the. K3v i1nhibitor is labelled to allow detection of th Kev1.3channel – inhibitor complex and the compound of in thve ntion can be adapted to in vivo or in vitroag dniostic use.Such label may be a detectable tag, in particu flaluro arophore tag. In this embodiment the binding complex may be dtet dec via the detectable tag. In an alternative example, the inhibitor compounfd th oe invention has a detectable label which isec dteatbleby an imaging method. For example, such detect labl eel can be a radioactive label. Methods like a threis describede.g. in WO2012 / 170392 A2. For example such methods for diagnosing T cell matedi disorders may be carried out by flow cytom,etrydistinguishing between various cell types by potpiounla specific staining and using such fluorophoargeg ted versions of the Kv1.3 inhibitor compounds to assess the anmt o (nuumber) of Kv1.3 channel proteins in each c aenll,d determining intensity distributions for the diffenrte cell populations thereby quantifying mean or mianed Kv1.3 specific fluorescence intensities for differentl c peolpulations. Another effective method to detect Kv1.3 potass ciuhmannel or to quantitatively measure the levele tohfe mr ay be carried out by immunohistochemical-like metho Idns. a preferred variant of this method a labellnedhib iitorcompound is used and thereby intensity of spec bif nicding of the miniprotein of the invention can d be tected bydetecting the signal provided by the label of tnhheib iitor compound. Both types are described in more detail in thet cehra “pMeasuring the level of Kv1.3”. Measuring the level of Kv1.3 The level of Kv1.3 can be measured by several mdesth konown in the art. Such methods can be utilizned i diagnosis of patients with diseases characterizye idnc breased Kv1.3 level on various cell types. Epxelamry methods are listed below. Measurement techniques are also useful in laboyra otro rresearch processes and such methods of tehnet i onnvare also contemplated. For example, measurement of cellular expression Kv o1f.3 channel protein can be carried out by using microscopy or flow cytometry, whereby the said a sucerf expression is assessed by determining then bgin odfi the labelled or tagged inhibitor with a staining meth uosded in immunocytochemistry or immunohistochemy.istr Flow cytometry For example, such methods for detecting T cellsre esxsping the Kv1.3 channel protein may be carrietd b oyu sorting or distinguishing between various cell tsyp ine vitro using such fluorophore tagged versiofns th oe Kv1.3inhibitor compounds for use in flow cytometry th cat n detect autoreactive cells.An example of flow cytometry assessment of Kv1.3pr ex ssion in experimentally activated rat and hum Tanlymphocytes was described by [Beeton C. et al.,32].00 In their flow cytometry experiments, ShK-F6CA a, fluoresceinated analog of ShK toxin, specificaltlyain sed Kv1.3-expressing cells with a detection t lim ofi ~600 channels per cell. Rat and human T cells that heaedn b repeatedly stimulated 7–10 times with a relte avnatnigen could be readily distinguished on the basis of their h leigvhels of Kv1.3 channels from resting T cells. Such methods are also disclosed e.g. in W020065 / 014 A212. Flow cytometry is suitable for charactergizi cnells in suspension wherein fluorescence activated coertliln sg is used to select living cells on the ba osfis characteristics measured by flow cytometry. In flow cytometry, cse mllay be distinguished and selected on the basis ze of and shape as well as by the presence of the fluorescenchee in ce tlls. In general, a flow cytometer uses focu lasesedr light to illuminate cells as they pass the laser beaml iunid a s ftream. Immunohistochemistry Tissue events of overexpression or elevating le ovfe Klsv1.3 can be studied by immunohistochemicalh modest on biological samples like tissue sections. In a variant of the method tissue sections area prreedp by any usual method and then primary anti-3Kv1. antibody is added; a secondary labeled (e.g. b-ciootninjugated or fluorescently labeled or enzyme-elidn)k antibody is added. Non-specific binding can be excluded bya rteinpge the method with no or non-specific antibod aiess a control.The binding of labeled secondary antibodies isa vlis zued by appropriate techniques. Example for m theisthod isdescribed by Rangaraju S et [ aRl.angaraju S. et al., 20]1.5 Immunohistochemical methods can be used in anyog biicoall sample though. Immunostaining of T-cellsm fro synovial fluid and tissue was used for Kv1.3 ansd a istsociated Kβv2 subunit by Beeton et a [lB.eeton C. et al., 200].6 Analogous methods can be carried out by usingn th iebi itor compound of the invention instead of prrimy aantibodies. In an embodiment a peptide conjugartiean vta of the invention is used wherein a labelo insj cugated to the polypeptide component to allow detection of bind.in Ing another embodiment a fusion protein is useder weihn thefusion partner may also serve as a detectable y m.o Fieotr example, the fusion partner may be a pro dtei tnectable bya secondary antibody. In another variant the fus piaorntner may be a protein detectable by its func,t eio.g. by an enzyme reaction or may be a fluorescent proteein g lirkeen fluorescent protein. Fusion proteins and conjugates are described ine m deotrail in chapters “Fusion proteins comprising1. K3v inhibitor polypeptide components” and in “Polypedpetsi conjugates of the invention”. Further imaging techniques As an example, Tem cell motility and interactionth w Ai PCs and collagen was visualized by a DTH immune response by two-photon imaging methodology, whe areftienr 24 h from the DTH challenge enlarged Temls c weel re highly motile along collagen fibers and continuoed m tigrate rapidly for 18 hr. Tem cells rely on vaoglet-gated Kv1.3 potassium channels to regulate calcium signalinyg t.h Bis method it could be shown that ShK-186, aci sfipce Kv1.3 blocker, inhibited DTH and suppressed Tem cellr egnelmaent and motility in inflamed tissue but had e nffoect on homing to or motility in lymph nodes of naive anedn ctral memory T (Tcm) cell [sMatheu MP et al., 200]8 The skilled person will understand that any imag tiencghnique for detecting Kv1.3 expressing cells b cean used for indirect measurement of the effect of Kv1.3ib inithor compounds of the invention. Kv1.3 expression by RNA-seq Kv1.3 (KCNA3) expression can be measured by RNAue senqcing to quantify transcriptional levels in immeu cnells, especially effector memory T (Tem) cells. Eleva KteCdNA3 expression is associated with inflammatorynd ciotions and can potentially be used for patient stratiifoicna,t helping identify individuals who may benefriotm f Kv1.3-targeted therapies. Combined methods of diagnosis and therapy by using the inhibiting compounds of the invention In particularly preferred embodiments of the invioen ,t once a disease is diagnosed in a subject,h w ihsicassociated with Kv1.3 channel activation, e.g.a ocvteivration or elevated levels, treatment of theje scutb in need thereof may be carried out by the Kv1.3 channel inhibit cinogmpounds of the invention. In a variant, diagnosis finds an elevated Kv1.3n cnheal activation in an early stage or a tendenc tyhe of patient to develop such disease and treatment is carrite tdo o purevent onset of the disease, i.e. by preven ptui rpose. In a particular embodiment both the diagnosis oef p thatient and treatment of the disease is carruietd by o an inhibitor compound of the invention, wherein diagsinso can be carried out e.g. by a method as desdc irnib cehapter “Diagnostic methods utilizing the compounds of i tnhveention” whereas treatment of a disease as dbeesdcr ini chapter “Therapeutic methods and administration” can berie cdar out by an appropriate method of treatment eb.yg. administering a pharmaceutical composition as dibeesdcr herein. A diagnostic compound of the invention and a redla thteerapeutic compound may form a so-called thesrtaicno pair. Here the diagnosis in a subject can be cdar oruiet by the inhibiting compound made suitable d fioargnosis, e.g.carrying an appropriate label, whereas an analog cou mspound adapted to therapeutic purpose, like c oanrreyingtargeting moiety or a stabilizing moiety, or oneic whh consists essentially of a miniprotein of thvee in tion, is usedfor therapy of the subject. Fusion proteins comprising Kv1.3 inhibitor polypeptide components The Kv1.3 potassium channel inhibitor compound m coamyprise additional amino acid sequences N-terminal and / or C-terminal of the Kv1.3 inhibitor compone Fnot.r example, the ion channel blocker may be aon fus piroteincomprising the Kv1.3 inhibitor and one or more o funsi partners, e.g. heterologous peptide or polydpep stei quences,which may be referred to as heterologous compo.nents In an embodiment the fusion partner may be a bgind minoiety such as an antibody or a fragment ther liekoef, an Fc or other fragment. The presence of a binding moiety may be usefualr igne tting the polypeptide component, e.g. minipnro otefithe invention to the disease site. In case of tianrge the fusion partner may allow the targeting th oef conjugate to atissue subject to disease, e.g. inflammation. The presence of a binding moiety may be useful u dpiaognnostic applications as well, provided that b thineding of the inhibitor polypeptide moiety of the invenntio binds to the Kv1.3 channel and such binding i bse to detected by a further binding interaction. The binding moiety may be an antibody or antibo fdraygment wherein one or more complementarity- determining regions (CDRs) comprise a peptide snecqeue derived from a potassium channel inhibitor,ra cchtaerized in that the peptide sequence is incorporated itn lteoa ast one CDR of the antibody, In preferred embodiment, the binding moiety may a bne Fc fusion protein, which involves linking the polypeptide having Kv1.3 inhibitor activity to th Fec region of an antibody to enhance stability aenrdum s half-life, In a further embodiment, the Kv1.3 inhibitor polypptiede component may also be inserted within a heterologous polypeptide, which may be regarde ad “ asscaffold” for the Kv1.3 inhibitor polypeptiden. I such cases, the ion channel inhibitor compound may be conside tore comprise heterologous components N- and Ci-ntearlm of the Kv1.3 inhibitor, wherein the heterologous comnepnots are derived from the same molecule and icntte wriath one another, e.g. to fold into a single scaffold, hagv tihne Kv1.3 inhibitor displayed at its surface. For example, the Kv1.3 inhibitor may be insertedth wini a surface loop of a heterologous protein, i en.tgo. the CDR sequence of an antibody or an antibody frag,m lieknet an Fc fragment, containing the antigen bningd diomain. Analogously, other binding molecules may be userd th foe same purpose. Such binding molecules may.g b.e e anticalins, flagellins, single domain antibodiekse li nanobodies etc. In certain embodiments, in particular in diagnos atpicplications the conjugating moiety may be a l,a wbehlichmay be particularly useful to detect the inhibi ctor mpound.Labels, as specific heterologous components maluyd inec tags such as a polyhistidine tag, FLAG tag M oycr tag or any fluorescent moiety. Another purpose of preparing a fusion protein meay to b further increase the stability, e.g. the hliafelf- of the compound of the invention. Exemplary half-life enxdteing moieties that can be used include well kno hwumnan serum albumin, transthyretin (TTR), a thyroxine-bindinlgob gulin TGB), albumin-binding domains, or an Fc fr oargments thereof.The skilled person will understand that the fus piorontein can be expressed in an expression systoem a frsingle nucleic acid encoding the fusion protein. If the polypeptide component is inserted into onrke lid to a large binding molecule, like an antibo tdhye, size of the Kv1.3 potassium channel inhibitor compounady m be as large as the fusion partner and the itnohri pboilypeptide component together, e.g. even in the order of 2D0a0 o kr 150 kDa in case of antibodies or the like is. I tto be noted that the inhibitor compound may be a part of eve lanrg aer protein complex. In preferred embodiments the fusion partners aned p tohlypeptide component are smaller, for exampele th fusion protein or the ion channel inhibitor compdou (npossibly also comprising conjugating moiety orors pthetic groups) may form a smaller protein having the lehn ogft a typical protein, e.g. about 400 amino ac oidrs 3,00 amino acids or even smaller e.g. in case of smaller bnignd miolecules, e.g. in the order of 200 amino ac oidrs 1,50 amino acids or the like. In an embodiment the polypeptide component, evethn f wlainking polypeptides at either the C-terminurs th oe N-terminus or both may be at most 100 amino ac oirds 7,5 amino acids or at most 50 amino acids or c moamyprise a few or a small number of amino acids or no furt ahmerino acids at its N-terminus or C-terminus. In a particular embodiment the fusion protein maey fu brther conjugated to provide additional funcatiolitnies. Polypeptides conjugates of the invention The compounds of the invention can be prepared f ionrm a of a conjugate of a polypeptide (polypeptide conjugate). In the conjugate any other moieties different fr tohme polypeptide of the invention can be used wh micahy also be referred to as heterologous components. Either the C-terminal or the N-terminal of the ppoelyptide can be conjugated. Upon conjugation the polypeptide or miniprotein mt ruestain its 3D fold and binding capability. In th eevent that the conjugated part would impair these proiepse,rt a linker may be required. The conjugating moiety, e.g. the heterologous conmepnot may comprise a prosthetic group. Among others, the prosthetic group may have al siztianbgi or half-live extending function. In an embodiment, the half-life extending moiety th oef fusion protein described herein is conjuga tote tdhe peptide antagonist of Kvl.3 via a linker. Exemplary half-life extending moieties that can u bse d include polypeptide, in this case chemicainllkye ld bya linker, such as inert globular proteins like hunm saerum albumin or the like. Sugar moieties such as polysaccharides may alsroov imep stability. Biologically suitable or tolerable polymers or colypmoers can also be used, for example ethylene gl,lyco polyethylene glycol (PEG) molecules, such as PEG05 o0r0 PEG20000, dextran, polylysine, fatty acidsf aanttdy acid esters of different chain lengths, for examplea lateu,r myristate, stearate, arachidate, behenataet,e o,l aerachidonate, octanedioic acid, tetradecanedioic acid, octadedciaonice acid, docosanedioic acid, and the like, oec,tan orcarbohydrates (dextran, cellulose, oligo- or poclycsha rides. In another embodiment, the half-lifee endxting moietyof the fusion protein described herein is humanum se arlbumin, albumin binding domain (ADB), or polhyyeltene glycol (PEG). Such molecules may also adapt solubility and thyer tiesbsue presence of the compounds of the inve.ntion A further purpose of conjugation may be to add t aec dteable label or tag to the polypeptide moiety th oef invention. Such detectable label may be e.g. are flsucoent compound. Alternatively, the detectable m taagy be a binding moiety which can be bound to a surfacey or a b binding molecule, like immunoglobulin, and tehbeyr the binding to the Kv1.3 channel can be detected iann adw sich assay. The detectable label or tag thus may be selecotemd t fhre group consisting of the following agentsu vailsization agents, preferably selected from fluorescent la,b realdsiolabels, magnetic resonance imaging labenlsd, a agents enabling indirect labeling by high affinity bindin tog labeling molecules. Labels, as specific heterologous components maluyd inec tags such as a polyhistidine tag, FLAG tag M oycr tag or any fluorescent moiety. In an embodiment the role of the conjugating parr itsne targeting or adding a further binding prope. rty In such cases the conjugating moiety may be an bgin mdioiety such as an artificial antibody analogc,h s aus a synthetic nanobody, a synthetic anticalin or anam apetr or a receptor ligand. Nucleic acids may also be used as binding agen tatsrg oerting moieties provided that they are bound nu bcyleic acid binding molecules. The presence of a binding moiety may be useful u dpiaognnostic applications as well, provided that b thineding of the inhibitor polypeptide moiety of the invenntio binds to the Kv1.3 channel and such binding i bse to detected by a further binding interaction. A label, which may be particularly useful to det tehcet inhibitor compound. In case of targeting the conjugating moiety mayow all the targeting of the conjugate to a tissue scutb tjoe disease, e.g. inflammation. Nucleic acids may also be used as labels allowipnegci sfic detection, e.g. by specifically binding oligonucleotides or by an amplification reaction. According to a further preferred embodiment of p thre sent invention, the conjugate comprises oneo orre mlinker(s) preferably one or more spacer(s) betw tehen polypeptide of the invention and the prosthe gtriocup. Thelinker may be selected from the group of peptidre asm oino acids, dimethyl disulfide linker, maleic g olurtaryl linker, enzyme-cleavable linkers like cathepsin-cleavaibnlkee lr. Preferably, the conjugate comprises one or mokre r li(ns) (linked to the R1 and R2 Site) and optioyn oanlle ormore spacer(s) between the polypeptide of the itniovnen and the prosthetic group. Another function of prosthetic groups may be to s soelutbility of the polypeptide component or eve fnus aion protein of the invention. Such solubility modifying prosthetic groups are. e p.oglymers, like polyethylene glycol (PEG) e.g. d aes cribedabove or small molecules. Sugar moieties such as polysaccharide are alsoul u tsoef improve or set solubility, e.g. to increaseate wr solubility. Lipids or lipidoids may increase the hydrophobicar cahcter of the inhibitor compounds. Such conjug mataeys also enhance membrane permeability or associaftio thne o compounds. Formulation and administration of pharmaceutical compositions The miniproteins or miniprotein moieties of thee inv tion can be formulated in any known way of poplytpideeor protein formulation, once they retain their 3oDld f. The compounds are active even without special folartmioun methods and can be provided e.g. in usufafelr bsu. The inhibitor compounds of the invention may bem fourlated with an appropriate polymer and polymer properties like monomer composition. Particulate formulations, a form of depot formuolanti strategies, include microparticles. Polymeric microparticles (MPs) are a particularly preferreedth mod for formulation of the present polypeptiden atgs. MPs canbe used for even controlled release and can bel matoedu by selecting the appropriate polymer andm poelry propertieslike monomer composition or molecular weight (MW [T)akeuchi I. et al. 201]7; for example, poly(dl-lactideco-- glycolide) (PLGA) and poly(l-lactidec-o-glycolide) (PLLGA) copolymers can be used where foars example hydrophobicity and glass transition temperatureat glyre affects drug releas [eTakeuchi I. et al. 201]7. PLGA formulated microparticles may be preparedo irnm fulations of various types, for example in inajebclet formulation or in topical formulation or in oralr fmoulations. An example for topical administratiofn a o potent and specific Kv1.3 peptide inhibitor in a Tem cell-maetdeid autoimmune skin disease, i.e. in an atopimca dteitris model is demonstrated by Olsen C. et [ aOl.lsen C. et al.201]7. A review is provided by Lagreca E. et al. fromic whh the skilled person will learn various methods of such formuolnat tiechnologies [Lagreca E. et al., 202].0 Other polymeric microparticles may be prepared fro pmolylysine, polyesters, polylactic acid (PLA),polycaprolactone (PCL), poly(ester amide), polyshac ricdes etc.The skilled person will also understand that selve arltaernative methods exist for the formulation of polypeptides. For example, Ibeanu N. et al. revie awppsroaches to optimize polypeptide delivery orzgeadni by the commonly used routes of administration and formiounlat echniques which may lead to successful devmeelonpt of proteins and peptides in clinic [sIb.eanu N. et al.202]0. Without limitation, various formulation strategi mesay further include the following techniques. Various methods, including preparation of emuls,io linkse oil-in-water or water-in-oil emulsions, asel wl as nanoprecipitation can be used. Preparation of gels are also an appropriate fortmiounla method wherein besides natural polymers, n liakteural polymers, such as collagen, chitosan, xanthan gum ar, gum and carrageenan, polypeptide-compatiblylem peors cambe used; among other polymers, e.g. of the follogw tyinpe, may be used for these type of solution wse alls: PLGA,PEG, poly(vinylpyrrolidone) (PVP), hyaluronic aci odr hyaluronan (HA) or poly(acrylamide) (PAM). Maxtri characteristics and compositions will define mat crhixaracteristics such as interactions with thep peoplytide, and mechanical strength. In the case of polymers, polymerization and croinsksi-nlg are important techniques to provide a fi sneatlting of the parameter [sIbeanu N. et al.202].0 The compositions of the invention are not inten tdoed be limited to any particular type of adminisitorant. Amedical practitioner will be familiar with method osf administration depending on the patient and m thoede oftreatment, such as subcutaneous, intravenous, etc. For administration of the pharmaceutical compons,iti ao suitable route is subcutaneous injection.x Ianm Eple 10 of the present description subcutaneous admraintiiosnt was applied. Intravenous administration is also contemplatede. c Tohmposition may be in liquid form, which is pcaurtliarlyuseful in case of i.v. administration. The compounds can be formulated for parenteraln aidsmtraition by injection e.g. by bolus injection in ofrusion. Also contemplated are implantable devices for tim reeledase of the pharmaceutical compositions. The pharmaceutical compositions can be made inlid a f soorm (including granules, powders or supposieitso)r or in a liquid form (e.g., solutions, suspensio onrs e,mulsions). Solid dosage forms for oral administration canu indcel capsules, tablets, pills, powders, and gra.n Iunle ssuchsolid dosage forms, the inhibitor compounds of in thve ntion can be admixed with at least one inelrute dnit such assucrose, lactose, or starch. The formulations mlasoy a comprise, other excipients with certain funncsti,o likelubricating agents, buffering agents, flavoring a cnodloring agents or coating. For nasal or pulmonary administration or any oth aedrministration by inhalation, the pharmaceuticalcompositions for use according to the invention f aore mulated, for example in the form of an aero ssporlay, whichmay be pressurized, or a nebulizer, with the us seui otafble propellant. The inhibitory compounds of the invention comprgisi tnhe polypeptide moiety can also be formulated a as depot preparation. Such long-acting formulationns b cea administered by implantation or by intramuasrcu inljection. The formulations may comprise an ion channel blorc okfe the invention, or a salt thereof, togetherh w ait carrier, excipient or vehicle. Accordingly, the compounds of the present inven,t oiorn salts thereof, especially pharmaceuticallye apctacble salts thereof, may be formulated as compositions ph oarrmaceutical compositions prepared for storarge o administration, and which comprise a therapeutyic eafllfective amount of a compound of the invention r, a salt thereof. As to salt formation the amphoteric nat oufr tehe peptide chain is to be considered. Typyic,a thlle polypeptide component of the invention comprises basic (likes, L Ayrg or possibly His) and acidic (like Glu or A)s rpesidues which provide, together with other weaklier prot doonnor or acceptor side chains, an isoelectric p (oIEinPt) for the polypeptides which is advisably taken into consaidtieorn upon formulation. For example, in liquid stoioluns a pH different from the IEP may be advisable to keep c tohmepound in solution. In creams and ointments., in e. egmulsions the pH may be closer to the IEP. Suitable salts formed with bases include metals, sa slutch as alkali metal or alkaline earth metatls, sa folr example sodium, potassium or magnesium salts;o asnsdib ply ammonia salts. It has been observed thlta sto slautions stabilize potassium channel inhibitor scorpionn tosx [Ni ikouee, A. et al, 201]5. Further organic amine salts can be used as wetellr.n Ianl salts may also be formed. Amino acid adndi stioalts can also be formed with amino acids, such as ly,s gilnyecine, or phenylalanine. Similarly, when a compound of the present inven ction tains a basic moiety, salts can be formed u osrignagnicor inorganic acids, preferably pharmaceuticallye apctacble acids. Such salts are well known in th.e art Over the last two decades, limitations regardinrgm fuolation and delivery of peptide drugs have beveenrc oomein several ways by introducing modification straietesg and the development of formulation and deliv setry ategies.Recently multiple reviews have been published whi icgh light the recent progress made in peptidev deeryli methodsimportant for their enhanced clinical efficacy. Wleh tihere is still room for further development a dnidscovery of particularly useful formulation strategies apt p toec sific peptides or uses, the skilled person wnildle urstand that in general working strategies can be found to typi fcoarml ulation or administration methods [B.arman P et al. 2023][Nugrahadi PP et al. 20]2[3Ghorpade, R et al.202].2 Pharmaceutical dosing The "therapeutically effective amount" of the postiuams channel inhibitor compound of the invention c bae determined by standard experiments in the fieldc.e O ann animal model exists for the particular diese, a fosr example inflammatory disease, the appropriate dose rannge be ca determined. In one embodiment of the invention, administrat oiofn a compound or pharmaceutical composition of the present invention is started at lower dosages,h w ahrice increased until the desired effect of preivnegn / ttreating the relevant medical indication is achieved. This wo dueldfine a therapeutically effective amount. The skilled person, e.g. a clinician would be aw oafre various factors to be taken into considerat wiohnen determining an optimal dosage for a given subj Seucct.h considerations are known to the skilled pe.r Bsoansically, the FDA Guidelines [Rockville, MD 2005] can be used. A more detailed discussion of thete mr iast provided by Nair and Jacob [Nair AB and Jacob S 201].6 For the compounds of the present invention, alorn aes o part of a pharmaceutical composition, sucha hnum doses of the active compound may be between ab.0o1ut p 0mol / kg and 50 µmol / kg body weight, between about 0.05 pmol / kg and 30 µmol / kg body weight, or between 0.1 pmol / kg and µ 5m0ol / kg body weight. Preferably the dose of the compound may be between 50 pmol / kg bodyh wte aignd 5 µmol / kg body weight or between 10 pmol / kg and 0.5 µmol / kg, or in a particular embodiment between 1m00ol p / kg and 100 nmol / kg. In the present invention pharmacokinetic evalua otiof n a set of structurally related selective Kv1n.3hib i itor peptides was tested by a single subcutaneous asdtrmaitnioin to male rats in a single subcutaneous doof s 1e mg / kg. The results were evaluated by blood collectionim aet- tpoints 5m, 15m, 30m, 1h, 2h and 4h. The abisoonrp otf the novel peptides was somewhat slower than for Daildaeza utsed as a reference, while the elimination w raatse almost an order of magnitude lower.mCaxand AUC values of the new peptides were 1-2 or odfe mrsagnitude higher compared to Dalazatide. Preparation of the miniproteins of the invention by synthetic methods The polypeptides of the invention can be syntheds bizye any suitable peptide synthesis method. In s ounceh method, Fmoc-amino acids peptide chemistry is u Aseltedr.natively, solid-phase peptide synthesis emyipnlgo a Boc- Bzl protecting group strategy may be utilized tsoe amsble the primary structure as well as analog thse o pf eptide. The peptide, once synthesized, is cleaved from thed s pohlai se by any appropriate method, e.g. by anhysd HroFu, yielding the linear peptide ready for folding as describbeodv ae for the Fmoc synthesized peptide. Such methods are described for example in WO 982 / 511 a1nd for example by Fields, G.B. et al., 2002, “Principles and practice of solid-phase peptideth seysnis”. In: Synthetic Peptides (2nd Edition) [Fdisel G.B. et al., 2002]. Solid phase peptide synthesis methods ca anut boemated. Automated peptide synthesis can als aopp bleied tolarger peptides or 30 to 40 amino acids, evenh fo sre t which are difficult to synthesiz [eW.inkler D.F. 2020, WinklerD.F. 2015]. A review of the protein and peptide synthesish modet is provided by Hou W et a [lH.ou W., 2017]. Recent peptide and protein synthesis protocols pr aorveided in the book of Jensen, K.N. et al. [ EJde.nsen, KN. et al. 2013]. Specific methods exist to prepare Cys-contain pienpgtides like deprotection using palladium compslexe [Kamo, N.2019] and peptide hydrazides as thioester surrog [Zatheesng JS 201]3. With peptide synthesis method also non-proteinogenic amino acids can be added anaslolygo tou protein-forming amino acids. For example, an ion channel blocker peptide ma syy bnethesized by a method which comprises synthegsizin the peptide by means of solid-phase or liquid-ph paespetide synthesis methodology and recovering e thpetid pe thusobtained. Thereby any polypeptide, e.g. the polytipdep component of the inhibitor compound can bepa pre d.Additionally, by modifying the precursor peptideri vaants of the ion channel inhibitor of the inventi coan be prepared. For example, the precursor peptide may be mod bifiyed introduction of one or more non-proteinogenicin aom acids (e.g. Nle), introduction of the appropriate termli gnraoups R1 and R2, etc. Non-proteinogenic amino acids Non-proteinogenic amino acids (NPAAs) can be usoerd d feveloping peptide-based drug candidates. Byintroducing NPAAs in the sequence of active pep-t yidpee agents, stability of the polypeptides can in bcereased or other features, like activity or bioavailabilityn fei-tuned. Nevertheless, undesired effects suchox aiscity t or immunogenicity should also be tested. A recente rwevi on non-canonical amino acids as building blo fcokrs peptidomimetics is available from Castro T.G. e.t [C aal stro TG 202]3. Without limitation, exemplary non-proteinogenic anmoi acids are listed below. In parenthesis, thee pinro-t forming amino acids (proteinogenic amino acids) r tehpelacement of which with the respective non-pinrootgeenic amino acids can be considered as a conservativlaec reempent, are given. In certain cases alternataivmee ns are given. The below exemplary non-proteinogenic amino acrides k anown and typically available from commerciaulr scoes. Norleucine (Nle), (methionine; Met, M); ((2S)-2-Aminohexanoic acid, Caprine), Sarcosine (Sar, MeGly), (glycine, alanine, Gly, G, Ala, A); (N-methylglycein, or monomethylglycine), α-aminoisobutyric acid (Aib), (valine, alanine, V, A) alpha-aminobutyric acid (Abu) (Alanine, Valine, A, V); (homo-alanine), norvaline (Nva) (Valine, Isoleucine, Leucine, V, I, L), 2,3-diaminopropanoic acid (Dap), (Lysine, K) 2,4-diaminobutanoic acid (Dab), (Lysine, K) 2,5-diaminopentanoic acid (ornithine; Orn) (,Lysine, K) homo-Lys (homo-lysine; hK, hLys) (,Lysine, K) homo-glutamine (hQ, hGln or homo-Gln) (Glutamine, Asparagine, Lysin Qe;, N, K); (6-oxolysine) Phenylalanine analogues: F(4-F) (4-fluoro-phenylalanine), Phe (F) F(4-NH2) (4-amino-phenylalanine), Phe (F) F(4-NO2) (4-nitro-phenylalanine), Phe (F) F(4-CH3) (4-methyl-phenylalanine) Phe (F) Citrulline (Arg, R) Beta-hydroxy norvalineβ (-OH-Nva) (Threonine, T); (3-Hydroxynorvaline) 3-Iodo-tyrosine for Tyrosine (3-I-Tyr) (Tyrosine, Y) Pipecolic acid (Pip (P)) (Proline, P) Azetidine-2-carboxylic acid (Proline, P) Preparation of the compounds of the invention by genetic engineering In the embodiment the inhibitor compounds of theven intion comprise a polypeptide consisting of proteinogenic amino acids only, the polypeptideu seenqce can be prepared by genetic expression me.thods Therefore, the invention also relates to a vecotomrp crising an isolated polynucleotide encoding tnhheib iitor compounds polypeptide of the invention. The met ihso adlso suitable to prepare fusion proteins whe trheein nucleotide sequence encoding the full fusion protein may boene cdl into an expression vector. The skilled person will understand that polynucildeeost encoding the polypeptides according to then intivon are available and can be synthesized. Expressinon ta ckae place as a longer polypeptide chain whicehn t chan be cut or digested to the desired size. In a preferredo edmimbent a fusion peptide is prepared accordinghe to n teed or design of the inhibitor compound. Expression of the peptide or precursor peptide f aro nmucleic acid encoding the peptide or precurseoprtid pe may be performed in a cell or a cell-free exprenssi yostem comprising such a nucleic acid. For recombinant expression, the nucleic acid frangtms e ncoding the precursor peptide will normally beinserted in suitable vectors to form cloning orr ex spsion vectors. The vectors can, depending ono psuer apnd type ofapplication, without limitation, be in the form p olfasmids, such as vectors derived from bacteraiaslm plids, phages such as bacteriophages, cosmids, mini-chromoso omre vsir,us e.g. baculovirus vectors; may be episom anadl- virus- derived, may comprise transposons, yeast episo emtce.s, Preferred cloning and expression vectors (plasmeicdto vrs) are capable of autonomous replication,e tbhyerenabling high copy-numbers for the purposes of- hleigvhel expression or high-level replication. Nevher ltess, properfolding of the miniproteins may be important andpr aoppriate environment, e.g. not overly fast expiroens / stranslation, avoiding oxidative environment, sufficient ionicre sntgth, may be necessary. An expression vector usually comprises at leasrotm a poter for driving expression of the nucleic a fcraidgment,the nucleic acid fragment encoding the precursoprtid pe , and optionally a nucleic acid sequence einc god aterminator. They may comprise additional featuruecsh s as selectable markers and origins of replinca.t Aiolso, a nucleic acid sequence encoding a leader peptidbelin egna secretion may be useful. Also, purificatiorn a offinity tags may be encoded by the nucleic acid. Host cells comprising the vector of the inventioany m be used to produce the peptide or precursorid pee.p Tthe cells used for expression can be cultured for pgraoptioan of the nucleic acid fragments and vectonrsd, / o ar used for recombinant production of the precursor peptidte ms.a Iy be that different cell lines are used forfe driefnt purposes. Preferred transformed cells are micro-organismhs s ausc bacterial cells. Typically, bacterial exproenss siystemsprovide high yields sometimes at the cost of impero fpolding, which may pose problem when complexio fnus proteinsare expressed. Alternatively, cells of multicelrlu olarganism can be used. Typical microorganism, preferably bacterial expiroenss systems are Escherichia (e g. E. coli), Basci (lleu g. Bacillus subtilis), Salmonella, or Mycobacteriumre (fperably non-pathogenic, e g. M. bovis BCG), ysea (set.g., Saccharomyces cerevisiae and Pichia pastoris)o.z Poraonts may also be applied. As eukaryotic expression system for example, with liomuitation insect cell, plant cells, or an anim caelll such as a mammalian cell can be applied. Secretion into the culture medium (or into the plearsim) may be preferred. Thus, or optionally ae niucc alcid sequence encoding a leader peptide enabling soencr metaiy be added to the N-terminal of the polypeep (t5id’ end of the coding sequence). Cells expressing the nucleic fragment can be uosre sdm fall-scale or large-scale preparation of thpetid pe s ofthe invention. The skilled person is well aware of molecular cnlogni and protein expression techniques to provide the expression vectors and host cells of the invention. Preparation of the compounds of the invention by a combination of recombinant methods and chemical modification The skilled person will understand that the inhoirbi ctompounds of the invention can be prepared by a combination of recombinant techniques and chem.is Ctrhyemistry may include peptide chemistry as debsecdri in thechapter “Preparation of the miniproteins of thee in tvion by synthetic methods” above and e.g. contijounga chemistrye.g. as described in the chapter “Conjugates o pfo thlyepeptides”. Recent techniques, methods and protocols regar thdeinrgapeutic peptides are taught and reviewed byon N,ix E.N. Ed. 2014 [Nixon, E.N.2014]. EXAMPLES EXAMPLE 1: Screening target protein production (KcsA-Kv1.x T+F) The Kv1.1, Kv1.2 and Kv1.3 (collectively denoted K avs1.x) T+F chimeras were prepared as follows: Expression of Proteins: pET45b expression plasmids carrying the codingue snecqes (SEQ ID NO: 59, 83, 84 and 85) for the Kv1.x T+F chimeras (Figure 2) were tranmsfoerd into C41(DE3 E). coli cells and cultured on lysogeny broth (LB) agar plates supplemented with carbenicillind a gnlucose. From each plate a single colony wasu ilnaotecd into the starter cultures and after overnight incubat aiotn 37 °C, 5-5 ml was inoculated into 0.5-0.5-lit LeBr media supplemented with carbenicillin, glucose and gloycle arnd cultivated at 37 °C at 200 rpm. When reagch minid-log phase (OD600: 0.6) the cell culture temperature t wapaesred to 30 °C, 5 mM Ba2C wl as added, then the cultures were induced for 3 h with 1mM Isopropyl ß-D-1-thiogaloapcytranoside (IPTG). Cells were pelleted by cengtraiftuion at 5000g for 10 min and stored at –20 °C. Protein Purification: The cell pellets were resuspended in lysis bu sffueprplemented with protease inhibitor cocktail tablets, then lysed by sonication, follongwi the clarification of the lysate by centrifuganti aot 20,000g for 15 mins. The supernatant was subjected to ultraceungtartifion with 100,00g0 for 1 h at 4 °C. The pelleted membrane fraction was resolubilized in resolubilization beurff (50 mM Tris, pH 8.0, 300 mM KCl, 5 mM imidazole) supplemented with 20 mM N-Dodecβy-l-D-maltoside (DDM). Resolubilized material was a uclterntrifuged at 100,000g for 1 h, and the supernatant was loaded onto ara HpiT TALON Crude chromatographic column pre- equilibrated with washing buffer (50 mM Tris pH 8, .3000 mM KCl, 2 mM DDM, 5 mM imidazole) and connedct to an Akta Pure chromatographic device. The loa cdoeludmn was washed with washing puffer, then bounadte mrial was eluted with a linear gradient (0-100%, in 1l0um con volume) of elution buffer (50 mM Tris pH 8.300,0 mM KCl, 2 mM DDM, 250 mM imidazole) in 1 ml elution fracntios. Fractions were analyzed by SDS-PAGE. Fractions containing the protein of interest were pooled a lonadded onto a HiLoad® 16 / 600 Superdex® 200 pg i glteralt fion column, pre-equilibrated with gel filtration / storeag buffer (20 mM Tris pH 8.0, 300 mM KCl, 2 mM DDM a)nd connected to an Akta Pure chromatographic devicluet.io En was done at 1 ml / min flow rate. Eluted pe fraakctions (1 ml) were analyzed by SDS-PAGE then pooled, cnotnraceted using a spin concentrator device. The cnotnracteion of the purified protein was determined by measur thineg UV absorbance at 280 nm. Purified protein sleasm wpere analyzed by SDS-PAGE before flash frozen and st aotre –d80 °C. The monomers and tetramers of the crhaism weere also identified by employing western blot using mseou anti-His monoclonal antibody against an N-teraml 6inxHis- tag on the chimeric proteins. To assess activit tyhe of produced target protein solutions, they weurbeje scted to phage ELISA using a dilution series of M13 bacteriopha dgiseplaying HgTx1, which inhibits with similarly hhig potency Kv1.1, Kv1.2, and Kv1.3 channels (The phage ELISinAd bing assay is detailed later). For immobiliza,tio pnrotein samples were diluted in gel filtration buffer. Th aepplied phage concentrations were ranging betwe0e9-n10111particle / ml. EXAMPLE 2: Generation of phage libraries and individual polypeptide-displaying phages Combinatorial phage-display libraries were genedra utseing sequences from native nonselective or maotedleyr selective Kv1.3 inhibitory peptides belonging toe t shame structural scaffold family (E.g.: MeKTX13- A2g,TX2, AgTX3, KTX1). Based on homology and feasibility csoidnerations, the amino acid sequences of the ch poespetnides were divided into three segments (denoted A, B, C a)n.d The segments were linked by sharing nucleo ctoiddees for the second cysteine (segment A and B) and foro tuhreth f cysteine (segment B and C). The DNA oligosrw (fard and reverse, in equimolar amount) coding for individu saelgment were custom synthetized and aliquoted t ihneto designated well of a 96 well plate. The librarya ctrioen was as follows: first, the oligos were phoosrpyhlated by T4 polynucleotide kinase (PNK) enzyme at 37 °C for m 3i0n. The phosphorylated oligos were annealed bytin hgea the samples to 95 °C, then they were tapered slowl 2y4 to °C. All annealed oligos coding for segment Ad, a Cn weremixed in equimolar amount, and this “supermix” w aadsded to separate ligation reaction tubes eachai cnoin gt a singleB segment coding oligo to facilitate successfurla lriby assembly. The segments were cloned into ar liizneed pAS62phagemid vector (SEQ ID NO:90) using the follow cinognditions: 16 °C for 16 h, followed by 65 °C fo5r m 1 in, thenthe reactions were stored for 4 °C. The final phmaigde construct harbored a signal sequence followye ad m bember of the miniprotein library, a linker sequence (GSASSRA,T SEQ ID NO: 62), and the C-terminal part of th3e c Poat protein. Next day, the ligation reactions weres trfaonrmed into individual aliquots of SS320 electrmocpoetent cells, following the standard protocol: electrocompeteenltls c were thawed on ice, mixed with the ligationac rteion, thensubjected to electroporation, after which the c welelsre immediately supplemented with pre-heatedv re rcyo medium,then pooled together in a single flask, and inceudba fotr 30 min at 37 °C. Next, the cell culture w inafsected with M13KO7 helper phage solution and was incubated an fo ardditional 30 mins, then the culture was inotceudla into 2YT (2x Yeast extract and pepton) media supplementethd c wairbenicillin and kanamycin. Next day, the ce ulllture was pelleted by centrifugation at 8,0g00 for 20 min, then the supernatant was suppleme wnittehd PEG-NaCl solution, andwas incubated at room temperature for 20 min. Trheeci p itated phage particles were pelleted by cfeungtarition at18,000g for 20 min, then resuspended in phageg seto brauffer (TBS containing 0.5% bovine serum albu,m ain d0.05% (v / v) Tween-20), centrifuged again to rem ionvseoluble materials, then the phage supernatant tr wanas ferredinto fresh tube, and stored at 4 °C. The phageic plear ctoncentrations of phage solutions were detneermdi by a spectrophotometer, and the concentration was aesdse ascscording to the formula: (O26D8-OD320) × 5 × 1012particles / ml. The quality of the phagemid libraryas w assessed by next generation sequencing, whnicfihrm ceod the presence of more than 1 million miniprotein varsia onft the theoretical 2.3 million members of thera lirby. For the creation of individual miniprotein displnagyi phagemid vectors and phage production, the mdoetlohgoy followed the same protocols described for phagep-ladyis library assembly. The three segments (A, B C a)nd coding oligos (forward and reverse) were ordered in setepa truabes as lyophilized products. Phosphorylatedd a annnealedoligonucleotides encoding the peptide constructe w liegrated into linearized pAS62 phagemid vecto ar v aetctor / insertratio of 1:3. Plasmid quality was assessed by Sra snegqeuencing. EXAMPLE 3: Library screening campaigns and identified hits For target protein immobilization, 0.2 µg / 50µl h oef t KcsA-Kv1.3 T+F chimera, 0.025 µg / 50µl of theA K-cKsv1.2 T+F chimera, and 0.1 µg / 50µl of the KcsA-Kv1.1 T c+hFimera protein coating solutions were used. Foartin cgo, wells of a Pierce™ Clear, 96-Well Nickel Coated Plate4 (4125, Thermo Fisher) were incubated with 50 µl voelusm of coating solution supplemented with 5 mM tetrabumtymlaonium at room temperature for 1 h. The plate b wloacskedfor additional 1 h at room temperature with 180w µel / l TBS-BSA (20 mM Tris, 150 mM NaCl, pH 7.5, 0.5 B%SA)supplemented with 1 mM DDM after target immobilizoant. Starting with the initial phage library andn ctionuing with each subsequent amplified phage library, 811x1 p0hage particles per well were add teod the wells and incubated for 1 h at room temperature on a horizontal shakerg.e Ph satock solutions were diluted to working concaetniotrn with phage resuspension buffer (TBS-BSA containing 0 v.1 / v% Tween 20 and supplemented with 2 mM DDM). Af ttheer phage incubation period, the wells were subjecote ad w tashing cycle, which involved 8 washes with 3µ0L0 of TBS- Tween washing buffer (20 mM Tris, 150 mM NaCl, p.H5, 70.1% v / v Tween 20), using a Wellwash Versao mpiclarte washer (Thermo Fisher). This was followed by antio enlu step using 0.1 M HCl. The eluted phages wesreed u to infect mid-log phase E. coli cells and were subsequenmtlpyli afied with helper phages as previously descri ibne tdhe libraryproduction. Panning and enrichment of binders aorsesi pble due to the physical and clonal link betw tehen displayedphage and its encapsulated DNA. This ensurese thleactt sing phages with desired traits also selecets co thrresponding DNA sequences, allowing for their enrichment. Tchreee sning campaigns consisted of five rounds of i pnagn:n the first three rounds were conducted consecutively using Kc thseA-Kv1.3 T+F chimera, followed by two addition raolunds carried out simultaneously on Kv1.3, Kv1.2, and K.1v.1 Utilizing the ISEP base idn silico counter-screening approach, the inventors identified hundreds of sequences e txhhaitbited continuous enrichment on the KcsA-Kv T1+.3F chimera while showing decrease, no enrichment, or very r leolwative enrichment on the KcsA-Kv1.1 and KcsA-K2v1 T.+F chimeras. This strategic selection process ens thuarets the chosen sequences demonstrate high spiteyc fiofirc Kv1.3, minimizing cross-reactivity with closely relateda cnhnels, which is crucial for advancing the speictyific of potentialtherapeutic interventions. From the hundreds onft id fie d sequences, the most promising hits — th woisthe the highestpredicted affinity and selectivity for the KcsA-K.v31 T+F — were selected and produced individually ph inage- displayed form. Table 1 shows the sequences ofh wh thice high KcsA-Kv1.3 T+F affinity and selectivit wyas confirmed by phage-ELISA binding assay. Table 1. Sequences identified CompoundSequenceSEQ ID NO 1 KEIPVKCKHSGQCLQSCKEAGMTYGKCMNGKCRCYSSEQ ID NO 2KEIPVKCKHSGQCLQSCKEAGMTYGKCMNGKCRCFSEQ ID NO 3KEIPVKCKHSGQCLQSCKEAGMTYGKCMNGKCRCFGRSEQ ID NO 4KEIPVKCKHSGQCLQSCKEAGMTYGKCMNRKCKCFGR SEQ ID NO 5 VRIPVSCKHSGQCLQSCKEAGMTYGKCMNGKCRCFGRSEQ ID NO 6VGINVKCTGSKQCLQSCKEAGMTYGKCMNGKCRCSKISEQ ID NO 7VGINVKCTGSKQCLQSCKEAGMTYGKCMNGKCRCFGRSEQ ID NO 8VGINVKCTGSKQCLQSCKEAGMTYGKCMNRKCKCFGRSEQ ID NO 9VGINVKCTGSKQCLQSCKEAGMTYGKCMNRKCKCYPRSEQ ID NO 10TIINEKCSGSRDCLQSCKEAGMTYGKCMNGKCRCFGRSEQ ID NO 11TIINEKCSGSRDCLQSCKEAGMTYGKCMNRKCKCFGRSEQ ID NO 12TIINEKCTGSKQCLQSCKEAGMTYGKCMNGKCRCFSEQ ID NO 13TIINEKCTGSKQCLQSCKEAGMTYGKCMNRKCKCFGRSEQ ID NO 14TIINEKCTGSKQCLQSCKEAGMTYGKCMNRKCKCYPRSEQ ID NO 15TIINEKCTGSKQCLQSCKEAGMTYGKCMNGKCRCFGRSEQ ID NO 16QIYTSKECTGSKQCLQSCKEAGMTYGKCMNGKCRCFGRSEQ ID NO 17QIYTSKECTGSKQCLQSCKEAGMTYGKCMNRKCKCFGRSEQ ID NO 18GVEINVKCSGSPQCLQSCKEAGMTYGKCMNRKCKCYPRSEQ ID NO 19GVEINVKCTGSKQCLQSCKEAGMTYGKCMNRKCKCYPRSEQ ID NO 20GVEINVKCSGSPQCLQSCKEAGMTYGKCMNRKCKCFGRSEQ ID NO 21GVPINVPCTGSPQCLQSCKEAGMTYGKCMNGKCRCFGRSEQ ID NO 22GVPINVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGRSEQ ID NO 23GVPINVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCYPRSEQ ID NO 24TIINEKCTGSKQCLQSCKEAGMRFGKCMNGKCRCFSEQ ID NO 25TIINEKCTGSKQCLQSCKEAGMTFGKCMNGKCRCFSEQ ID NO 26TIINEKCTGSKQCLQSCKEAGMRYGKCMNGKCRCFSEQ ID NO 27TIINEKCTGSKQCLQSCKEAGMTYGKCMNRKCKCFSEQ ID NO 28TIINEKCTGSKQCLQSCKEAGMTYGKCMNRKCRCFSEQ ID NO 29GVPINVPCTGSPQCLQSCKEAGMTYGKCMNGKCKCFGRSEQ ID NO 30GVPINVPCTGSPQCLQSCKEAGMRFGKCMNRKCKCFGRSEQ ID NO 31GVPINVPCTGSPQCLQSCKEAGMTFGKCMNRKCKCFGR SEQ ID NO 32 GVPINVPCTGSPQCLQSCKEAGMRYGKCMNRKCKCFGRSEQ ID NO 33GVPINVPCTGSPQCKQSCKEAGMTYGKCMNRKCKCFGRSEQ ID NO 34GVPINVPCTGSPQCLESCKEAGMTYGKCMNRKCKCFGR SEQ ID NO 35 GVPINVPCTGSPQCLKSCKEAGMTYGKCMNRKCKCFGRSEQ ID NO 36GVPINVPCTGSPQCLQKCKEAGMTYGKCMNRKCKCFGRSEQ ID NO 37INVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGRSEQ ID NO 38VPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGRSEQ ID NO 39CTGSPQCLQSCKEAGMTYGKCMNRKCKCFGRSEQ ID NO 40GVPINVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFSEQ ID NO 41GAPINVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGRSEQ ID NO 42GVPANVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGRSEQ ID NO 43GVPINVPCTASPQCLQSCKEAGMTYGKCMNRKCKCFGRSEQ ID NO 44GVPINVPCTGSPQCLQACKEAGMTYGKCMNRKCKCFGRSEQ ID NO 45GVPINVPCTGSPQCLQSCKEAGMTYGKCMNKKCKCFGRSEQ ID NO 46GVPINVPCTGSPQCVQSCKEAGMTYGKCMNRKCKCFGRSEQ ID NO 47GVPINVPCTGSPQCLQSCKEAGMTFGKCMNRKCKCYGR EXAMPLE 4: Characterization of hits in phage displayed form by phage ELISA binding assay The phage displayed form is particularly usefu als tosess binding to the various K channels, wher reeinla ativelylarge number of sequences can be tested coste-enftfliyc.i In the present invention, the identified u se nqces wereevaluated for their effectiveness as Kv1.3 inhirbsito by comparing them to known benchmarks: MeKTX1,3 a-2 recognized low-affinity and low-selectivity Kv1.3nh iibitor, and Vm24, a phage-displayed peptide no foterd its high affinity and moderate selectivity [Varga e Zt. al., 2012; Kuzmenkov A. I e.t al., 2015]. The sequences (from SEQ ID NO: 1 to SEQ ID NO: w 4e7r)e tested in the phage ELISA binding assay using the KcsA-Kv1.3 T+F, and the off targets KcsA-Kv1 T.+2F, KcsA-Kv1.1 T+F. Coating and phage incubatinon th ie phage-ELISA procedure was similar to that in thnen pinag process except that for protein immobiliznat tihoe following amounts were used in a final volume of 50 µl / w Keclls:A-Kv1.1 T+F: 0.01 µg, KcsA-Kv1.2 T+F: 0.01 µgn,d a KcsA- Kv1.3 T+F: 0.05 µg. For phage incubation 39*1 p0hage particles / well was use Tdh.e plate was washed only 4x with washing buffer, then 50 µl anti-M13 IgG HRP (MA51-3265, Invitrogen) diluted 1:2500 in TBS-Tween (0.1 v% / v) was added to the wells and incubated for 1 h amt ro teomperature. The plate was washed again 4x w0i0th µ 3l / wellwashing buffer. Finally, 50 µl / well 1-Step Ultra TBM-ELISA solution (34028, Thermo Scientific) was aedd to thewells, and the developing signal was stopped w0ith µ 5l 1M HCl after 5 minutes. The light absorbancigena sl (3 parallel measurements) was read at 450 nm witho ano Byy absorbance 96 plate reader (Byonoy GmbH). The binding intensities were evaluated based oonr abbasnce (OD450), which is proportional to the numr obfe bound phages within limits of the ELISA assay. Table 2 shows the relative KcsA-Kv1.3 T+F bindinfg se oquences compared to MeKTX13-2, and their rveelati selectivity values over KcsA-Kv1.2 T+F and KcsA-K.1v1 T+F proteins. The relative binding selectivisty th ie ratio of absorbance values Kv1.3 / Kv1.2 or Kv1.3 / Kv1.1e (th igher the better). However, it is worth notinhgat t these selectivity values obtained at a uniform conceniotrnat are not proportional to the selectivity valu tehsat can be established from IC50 values based on the chanlnocekli bng effects. They are only approximate indicrsato f the ranking of selectivity compared either to eachr ot ohre to the benchmarking compounds MeKTX13-2 and2 V4.m For example, SEQ ID NO:2 showed 4.81-fold selectiviotyr K f v1.3 over Kv1.1 in phage binding assays (Ta 2b)l,e but more than 100-fold selectivity for channel-blocki enfgfects (see Table 4). It is also known for ale sdkil person that, in general, binding affinity to target proteins is naolwtays proportional with potency of functionale ecftfs such as channel blocking. Nevertheless, binding can predict funncatilo effects with good probability. Table 2. KcsA-Kv1.3 T+F binding and selectivity in phagend biing Relative Phage Binding Selectivities Intensities (Intensity / Intensity) Compound Relative KcsA-Kv1.3 Relative KcsA-Kv1.3 Relative KcsA-Kv1.3 T+F binding compared T+F selectivity over T+F selectivity over to MeKTX13-2 KcsA-Kv1.2 T+F KcsA-Kv1.1 T+F MeKTX13-21.00 1.22 1.05Vm248.03 1.98 9.01 SEQ ID NO 10.90 2.68 2.50SEQ ID NO 28.33 22.91 20.25SEQ ID NO 38.44 19.65 13.90SEQ ID NO 411.26 19.61 11.10SEQ ID NO 511.90 8.55 4.81SEQ ID NO 68.56 19.26 6.73SEQ ID NO 711.67 4.81 3.72SEQ ID NO 88.28 3.36 2.96SEQ ID NO 98.45 8.59 3.24SEQ ID NO 103.05 3.13 3.18SEQ ID NO 116.88 5.23 5.82SEQ ID NO 1211.99 22.83 23.00SEQ ID NO 135.72 14.47 13.52SEQ ID NO 1410.34 11.27 5.17SEQ ID NO 1510.34 14.68 13.65SEQ ID NO 1610.34 5.83 5.50SEQ ID NO 1710.90 6.26 7.16SEQ ID NO 184.66 16.48 9.24SEQ ID NO 197.64 13.33 6.54SEQ ID NO 2011.03 22.17 18.00SEQ ID NO 212.47 10.37 10.98SEQ ID NO 229.16 41.60 33.36SEQ ID NO 238.28 29.73 6.07SEQ ID NO 245.01 8.70 6.73SEQ ID NO 252.17 3.26 3.07SEQ ID NO 2613.13 8.07 5.65SEQ ID NO 2711.57 12.68 11.09SEQ ID NO 2812.17 10.92 9.52SEQ ID NO 295.96 25.66 28.25SEQ ID NO 304.00 14.38 3.86SEQ ID NO 315.36 18.12 9.08SEQ ID NO 3210.04 16.20 4.06SEQ ID NO 335.40 5.48 6.02SEQ ID NO 343.77 10.15 9.54SEQ ID NO 359.76 23.82 22.86SEQ ID NO 369.88 10.82 7.24SEQ ID NO 379.33 18.91 8.40SEQ ID NO 389.78 34.29 24.49SEQ ID NO 398.17 26.10 19.94SEQ ID NO 407.48 30.17 29.54SEQ ID NO 419.81 6.47 3.84SEQ ID NO 4210.00 11.86 8.58SEQ ID NO 439.37 23.08 16.54SEQ ID NO 4410.06 14.15 9.97SEQ ID NO 459.38 6.55 5.11SEQ ID NO 465.83 3.32 8.76SEQ ID NO 476.82 3.32 2.41The comparative analysis revealed that all teseteqdue snces demonstrated superior selectivity comp taored MeKTX13-2 and Vm24. Except SEQ ID NO: 1, all seqcueesn demonstrated significantly higher KcsA-Kv1.3F T+ binding intensity compared to MeKTX13-2. Additionlya,l some sequences either matched or surpasse Kdv t1h.e3 affinity observed with Vm24, indicating their poteianl as highly potent Kv1.3 inhibitors. EXAMPLE 5: Method of production and sequences of polypeptide compounds obtained in free miniprotein form A representative set of compounds from the pre insevnent tion, along with reference compounds, weredu pcroed either recombinantly or synthetically. Additiona,ll tyhree reference compounds—AgTx3, KTX1, and Datildaeza— were obtained from Alomone Labs. One reference cooumndp (Moka1) was produced in-house via recombinant expression, and another (si-544) was sourced froemCh Mem Express.These compounds along with the mfode o obtaining and their amino acid sequences are lis nte Tdable 3. Miniprotein expression and purification: For the recombinant production of miniproteinse,ir th corresponding DNA sequences were cloned into a pET-based expornes pslai smid as a C-terminal fusion to the DsbC (ldfidiseu isomerase C) fusion protein and the WELQ recogni stiiote of the staphylococcal serine protease S TphlBe. construct also encoded for an N-terminal 6xHis-tag recognit sioite for downstream applications. Chemically competent Shuffle T7 Express E. collis c (eNl ew England Biolabs) were transformed with s theequenceverified expression plasmid. Transformed cells w setre aked onto LB-agar plates supplemented with µ 1g0 / 0mLcarbenicillin (Car) and incubated at 37°C overnig nh at stationary incubator. A single colony wasec seteld to inoculate the LB-Car starter, which was grown overnight a°tC 3.0 The following large scale cell culture (inoctuelda with 1:100starter) was grown until mid-log phase at 37°C in sh a ker incubator at 200 rpm then induced with 1m IPMTG(Isopropyl β-D-1-thiogalactopyranoside). IPTG induced exprenss wioas performed at 28°C for 16 hours. Cells were pelleted by centrifugation at 5000g for 10 min.le Ptel was resuspended in ice-cold lysis buffer (PB pHS,:7.4, supplemented with 200mM NaCl and 0.3% Triton X-1 a0n0d) cells were disrupted with an ultrasound sotonric (a5min, 6:12 pulse, 65% amplitude). Cell lysate was ceungtreifd at 20,000 g for 20 mins and supernatant warisfie pdu by IMAC (Immobilized Metal Affinity Chromatography cohmr atography) using AKTA Pure chromatographic sys,tem HisTrap™ High Performance Cytiva column (Sigma, G7-E51248-01) and gradient elution of buffer A (PBS:7 p.H8 supplemented with 200mM NaCl and 5 mM imidazoled) a bnuffer B (PBS pH:7.8 supplemented with 200mM NaCland 500 mM imidazole). Product containing fractio wnesre collected and dialysed against 10mM pH: 7E.4P HES buffer using Amicon stirred cell under argon preress.u The concentration of the fusion protein wass mueread (UV absorbance at 280 nm) by NanoDrop Microvolume Sroppehctotometer. WELQut protease was added (1:10 enzyme / substrate ratio) to the fusion protein anzdym eatic mixture was incubated for 24h at 25°C w gitehntle agitation to remove the fusion tags from the peep.ti Cdleaved peptide solution was purified by IEXn (I eoxchange chromatography) using AKTA Pure chromatographicte smys, HiScreen SP HP Cytiva column (Sigma, 28950515) and gradient elution of buffer A (10mM sodium phhoastpe buffer pH:7.2) and buffer B (10mM sodium phhoastpe buffer pH:7.2 supplemented with 1 M NaCl). Pept cidoentaining fractions were further purified by Jas HcPoLC system using Teknokroma Europa Peptide C8 column ande gnratd eilution of Buffer A (H2O +0.1% formic acid) an Bduffer B (90% acetonitrile, 10% H2O +0.1% formic acid).ri Pfieud peptide solutions were aliquoted and lyoipzheidl. Peptides were analyzed by LC / MS. Miniprotein synthesis and folding: Synthetic peptides were produced by Fmoc solids-eph paeptide synthesis carried out at different contract manufacturinga onrigzations (e.g. MedChemExpress, Solid Science. P Ulncf)oldedpeptides were folded in glutathione redox buffesrte smy (10mM TRIS, 100mM NaCl, 5mM GSSG, 5mM GSH, pH: 8.0). Peptides were incubated in folding buffe 2r a mtg / ml concentration for 16 h at 25°C. Folded pideep stolution waspurified by Jasco HPLC system using Teknokroma p Eaur Poeptide C18 column and gradient elution of Bru Affe (H2O supplemented with 0.2% v / v acetic acid and % 0. v1 / v of 32% w / v ammonia stock solution) and Burf Bfe (90% acetonitrile and 10%2HO, supplemented with 0.2% acetic acid and 0.1 % am omf onia stock solution). Purified peptide solutions were aliquoted and lyophilized. Pepti wdes re analyzed by LC / MS.Table 3. Polypeptide compounds obtained in free minipro ftoerinm Recombinant or synthetic Compound Sequence production or Purchased SEQ ID NO: 2 Recombinant KEIPVKCKHSGQCLQSCKEAGMTYGKCMNGKCRCF^^ SEQ ID NO: 5 Recombinant VRIPVSCKHSGQCLQSCKEAGMTYGKCMNGKCRCFGR^^ SEQ ID NO: 9 Recombinant VGINVKCTGSKQCLQSCKEAGMTYGKCMNRKCKCYPR^^ SEQ ID NO: 11 Recombinant ^TIINEKCSGSRDCLQSCKEAGMTYGKCMNRKCKCFGR^^ SEQ ID NO: 12 Recombinant ^TIINEKCTGSKQCLQSCKEAGMTYGKCMNGKCRCF^^ SEQ ID NO: 17 Recombinant QIYTSKECTGSKQCLQSCKEAGMTYGKCMNRKCKCFGR^^ SEQ ID NO: 20 Recombinant GVEINVKCSGSPQCLQSCKEAGMTYGKCMNRKCKCFGR^^SEQ ID NO: 22 RecombinantGVPINVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGRSEQ ID NO: 26 Recombinant TIINEKCTGSKQCLQSCKEAGMRYGKCMNGKCRCF^^ SEQ ID NO: 29 Recombinant GVPINVPCTGSPQCLQSCKEAGMTYGKCMNGKCKCFGR^^ SEQ ID NO: 30 Recombinant GVPINVPCTGSPQCLQSCKEAGMRFGKCMNRKCKCFGR^^ SEQ ID NO: 32 Recombinant GVPINVPCTGSPQCLQSCKEAGMRYGKCMNRKCKCFGR^^ SEQ ID NO: 34 Recombinant GVPINVPCTGSPQCLESCKEAGMTYGKCMNRKCKCFGR^^ SEQ ID NO: 35 Recombinant GVPINVPCTGSPQCLKSCKEAGMTYGKCMNRKCKCFGR^^ SEQ ID NO: 36 Recombinant GVPINVPCTGSPQCLQKCKEAGMTYGKCMNRKCKCFGR^^ SEQ ID NO: 37 Recombinant INVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGR^^ SEQ ID NO: 38 Recombinant VPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGR^^ SEQ ID NO: 48 Synthetic GVPINVPCTGSPQCLQSCKEAG(Nle)RYGKC(Nle)NRKCKCFG-amide^ SEQ ID NO: 49 Synthetic GVPINVPCTGSPQCLQSCKEAGMRYGKCMNRKCKCFGR-amide^^ SEQ ID NO: 50 Synthetic GVPINVPCTGSPQCLQSCKEAGMRYGKCMNRKCKCFG-amide^ SEQ ID NO: 51 Recombinant GVPINVPCTGSPQCLQSCKEAGMRYGKCMNRKCKCFG^^ SEQ ID NO: 52 Synthetic GVPINVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGR-amide^^ SEQ ID NO: 53 Synthetic GVPINVPCTGSPQCLQSCKEAG(Nle)RYGKC(Nle)NRKCKCFG^^ SEQ ID NO: 54 Recombinant GVPINVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFG^^ SEQ ID NO: 55 Synthetic GVPINVPCTGSPQCLQSCKEAG(Nle)TYGKC(Nle)NRKCKCFGR^^ SEQ ID NO: 56 Recombinant GVPINVPCTGSPQCLQSCKEAGMTYGKCMNGKCKCFG^^SEQ ID NO: 57 SyntheticGVPINVPCTGSPQCLKSCKEAGMRYGKCMNRKCKCFG-amideKTX1PurchasedGVEINVKCSGSPQCLKPCKDAGMRFGKCMNRKCHCTPK (SEQ ID NO:58) AgTx3 Purchased GVPINVPCTGSPQCIKPCKDAGMRFGKCMNRKCHCTPK^ (SEQ ID NO:59) MeKTx13-2 Recombinant REIPVKCKGSKQCLQSCKEAGMTYGKCMNGKCNCTPKG^ (SEQ ID NO: 60) DalazatidePurchased[pTyr][AEEA]RSCIDTIPKSRCTAFQCKHSMKYRLSFCRKTCGTC-NH (SEQ ID NO: 61) si-544SyntheticTIINVKCTSPKQCLPPCKAQTGCPYGKCMNRKCKCNRC (SEQ ID NO: 91) Moka1RecombinantINVKCSLPQQCIKPCKDAGMRFGKCMNKKCRCYS (SEQ ID NO: 92) EXAMPLE 6: Characterization of sequences in miniprotein form by electrophysiology Human Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv1.5, Kv11.1 an KdCa3.1 channel blocking potencies of miniprotein compounds were assessed by whole cell patch-clasmsapys a. Cells for patch-clamp recording: For Kv1.1 and Kv1.2, Kv1.4, Kv1.5, and KCa3.1 triaens tly transfected Chinese Hamster Ovarian (CHOlls) cewere used. Cells were grown in DMEM-high glucospep sleumented with 10% FBS, 2 mM L-glutamine, 100 U / mL penicillin G, and 100 μg / mL streptomycin (Invitrogen) at 37 °C in a 5% CO an2d 95% air humidified atmosphere. Cells were passaged twice per week following an 5 i mnciubation in PBS containing 0.2 g / L EDTA. CHOlls ce were transiently transfected with plasmids encoding h.K1v,1 hKv1.2, hKv1.4, hKv1.5, or hKCa3.1 in pCMV6-AGCF-P plasmid (Cat# RC211000, RC222200, RC220205, RC231,9 R79C204457 OriGene Technologies, Rockville, MD) using Lipofectamine 2000 (Invitrogen, Carlsbad, C foAl)lowing the manufacturer’s protocol, then cueltdur under standard conditions. Transfected cells were was twheicde with 2 mL of extracellular solution (ECS, s bee low) andre-plated onto 35 mm polystyrene cell culture dsis (hCeellstar, Greiner Bio-One) before the patch cpla emxperiments. At 24 h after transfection GFP expressing transafnetcst were identified with NikonTE 2000U fluorescen mcicroscope(Nikon, Tokyo, Japan) using bandpass filters of- 4595 nm and 515-555 nm for excitation and emiss rieosnp,ectivelyand used for current recordings (~60-70% succetess fo rar co-transfection). In general, currents w rer ceorded 24 to36 h after transfection. hKv1.3 currents were recorded from activated perriaplh blood mononuclear cells (PBMCs, see below) 3–4 days after activation. Heparinized human periph veeranlous blood was obtained from healthy volunte Meorsn.onuclear cells were separated through Histopaque-1077 dye gnrsaidtient centrifugation. Collected cells wereh weads twice with Ca2+ and Mg2+ free Hanks’ solution containing 25 m HMEPES buffer, pH 7.4. Cells were cultured for 34 t doays in 24-well culture plates in a 5% CO2 incubator 37 at °C, in RPMI 1640 medium supplemented with 10%tal f cealf serum (Sigma-Aldrich), 100 μg / ml penicillin, 100 μg / ml streptomycin, and 2 mM L-glutamine (density.5, 0 x 106 cells per ml). Phytohemagglutinin A (PHA, Sigma-Aricldh) was added to the medium at μ 1g0 / mL to amplify the Kv1.3 expression. Cells were washed gently twicteh w 2i mL of ECS for the patch-clamp experiments. hKv11.1 currents were recorded from HEK 293 cetlalsbl sy expressing the hKv11.1 channel. Whole-cell patch-clamp recording: Conventional whole-cell patch-clamp electrophysgioylo was used to record ionic currents. Micropipe wttes repulled from GC150F-7.5 borosilicate capillariesr (vHaard Apparatus, Kent, UK) with tip diameters beetwne 0.5 and 1 μm resulting in a tip resistance of 2-8Ω M in the extracellular (bath) solution. All measureenmts were carried out by using Axopatch 200B amplifier connected to a pearslo cnomputer using Axon Digidata 1550A data acqiuoinsit hardware and Pclamp 10.7 software. The holdingn ptioatle was 120 mV. Records were discarded when a leta tkheholding potential was >10% of peak current at tehset p t otential. Experiments were performed at roeom p terature(20-24°C). Before analysis, whole-cell currente trsac were corrected for ohmic leakage and digitailltleyr fed with a three-point boxcar smoothing filter. Solutions: For recordings Kv1.1, Kv1.2, Kv1.3, K4v1 a.nd Kv1.5, the extracellular (bath) solution (E)CS contained 145 mM NaCl, 5 mM KCl, 2.5 mM CaCl2, 1 m MMgCl2, 10 mM HEPES, and 5.5 mM glucose (pH 7.35 with NaOH), while the intracellular (pipette) soiolunt (ICS) contained 140 mM KF, 2 mM MgCl2, 1 mM Cl2a,C 11 mM EGTA, and 10 mM HEPES (pH 7.22 with KOH). Focro rerdings of hKv11.1 currents, the ECS contained 140 mM choline-chloride, 5 mM KCl, 2 mM MgCl2, 2 mM Cal2C, 0.1 mM CdCl2, 20 mM glucose, and 10 mM HEPES (pH 7.35 with NaOH) and the ICS contained 140 mMl, K 1C0 mM EGTA, 2 mM MgCl2, and 10 mM HEPES (pH 7.3 with KOH). hKCa3.1 currents were recorded w ainth ECS of the following composition: 160 mM L-astpica arcid sodium salt, 5 mM KCl, 2.5 mM CaCl2, 1.0 mM MgCl a2n,d 10 mM HEPES (pH 7.4 with NaOH), while the composition of ICS was 150 mM L-aspartic acid psoituams salt, 5 mM HEPES, 10 mM EGTA, 8.7 mM CaCl2d, an 2 mM MgCl2 (pH 7.22 with KOH) giving ~2 µM free C+a2 to fully activate the KCa3.1 current. The osmiotyla orf the ECS and ICS were 302–308 mOsM and ~ 295 mOessMp,e rctively. The test substances and positiveo closn wtrere dissolved in ECS supplemented with 0.1 mg / mL bov sienreum albumin (BSA; Sigma-Aldrich Hungary, Budatp,es Hungary). Bath perfusion around the measured ciethll d wifferent extracellular solutions was achiev uesding a gravity flow micro perfusion system using a rate of 0.5 miLn / . Excess fluid was removed continuously. Voltage protocols: For measurement of hKv1.1–1.r5re cnuts, voltage steps to +50 mV were applied from a holding potential of –120 mV and the peak curreanst w measured every 15 seconds. For Kv1.3 curre5n-tms,s 1-long depolarizing pulses were applied. For Kv1.1 and. K4,v150-ms-long activating stimuli were used. Kv1 a.n2d Kv1.5 currents were evoked by 200-ms-long pulses. For1 K.1v1 channels, currents were evoked with a voltategpe t so +20 mV followed by a step to –40 mV, during which theea pk current was measured. The holding potential – w8a0s mV,and pulses were delivered every 30 s. hKCa3.1n ctusrr weere elicited every 15 s with voltage ramp +s5 to0 mV froma test potential of –120 mV at a rate of 0.85 mV. / Tmhse holding potential was set to –85 mV. Positive controls were applied at a concentratiqouniv ealent to their IC50 values (0.3 mM and 10 mMA T+E for Kv1.1 and Kv1.3, respectively, and 14 nM chadroytboxin (ChTx) for Kv1.2, or high K+ ECS (HK) soilounts for KV1.4 and KV1.5). Evaluation: The remaining current fraction (RCF a) a gtiven molar concentration was calculated as, w I / Ih0ere I0 is the peak current in the absence, and I is pe thaek current at equilibrium block or in the absee onfc inhibition after ~2 min perfusion by the investigated compound. e Pnetrc inhibitions (I%) were calculated as (1–RCF)x.10 F0or assessing approximate fifty percent inhibitory ceonntcrations (IC50 values) of the miniprotein tesbts stuances on Kv1.3 channels, their channel blocking effects (I w%e)re tested in 3-5 (per concentration) single we-hcoelll patch- clamp recording experiments at given concentra.tio Anpsproximate IC50 values were determined based th oen observed percent inhibition (I%) and by assumin sgta andard sigmoidal dose-response relationship.e T ehsetsimations were made relative to the inhibition profiles obvseedr for Kv1.2 and Kv1.1 channels. Approximate IC v5a0lues were estimated from the average I% values at 2 or 3 c toensctentrations assuming a sigmoidal curve fit atinccgording to the following equation 2: where Bottom = 0, Top=100, HillSlope=1 and X=I%. For assessing selectivity of the compounds of pnrte insevention, their blocking effect on all chann oetlsher than hKv1.3 was uniformly tested at test concentratiof n 10 o00 nM. The blocking potencies of the testedip mrionteins on human Kv1.3, Kv1.2, and Kv1.1 channels, expresse pde arcent inhibition and estimated IC50 values, p areresented in Table 4. In addition, their selectivity for Kv31. channel blocking over Kv1.2 and Kv1.1 (i.e. IC15.0x- / IC50-1.3, where IC50-1.x is the lower of IC50-1.2 and IC501-)1 c.hannel blocking is also indicated. The res suhltosw that all the representative compounds supporting the gen foerrmalula in Paragraph 2 of ‘Brief description ofe th invention’ are all >100-fold selective for Kv1.3, and major oitfy them is >1000-fold selective. Table 4. Kv1.3 blocking potency and selectivity of miniperoints tested by patch-clamp T.he notation "<x nM" indicates that inhibition is greater than0% 5 at x nM concentration but not greater than 50t% x / 1 a0 nMconcentration. The notation ">x nM" indicates th inahtibition is greater than 10% but less than 50% x a ntM. Thenotation ">>x nM" indicates that inhibition is le tshsan 10% at x nM. (Here, IC50Kv1.x stands for l tohweer value of the IC50s on Kv1.1 and Kv1.2.) Kv1.3 Kv1.2 Kv1.1 Selectivity Compound (IC50) (IC50) (IC50) (IC50Kv1.x / IC50Kv1.3) MeKTx13-2>100 nM >>1000 nM <1000 nM <10xSEQ ID NO 2<100 nM >>1000 nM >>1000 nM >100xSEQ ID NO 5<100 nM >1000 nM >>1000 nM >100x SEQ ID NO 9<10 nM >1000 nM >1000 nM >1000xSEQ ID NO 11<10 nM >>1000 nM >>1000 nM >1000xSEQ ID NO 12<100 nM >>1000 nM >>1000 nM >100xSEQ ID NO 17<10 nM >>1000 nM >>1000 nM >1000xSEQ ID NO 20<10 nM >>1000 nM >>1000 nM >1000xSEQ ID NO 22<1 nM >>1000 nM >>1000 nM >1000x SEQ ID NO 26<10 nM >>1000 nM >>1000 nM >1000xSEQ ID NO 29<100 nM >>1000 nM >>1000 nM >1000xSEQ ID NO 30<1 nM >1000 nM >>1000 nM >1000xSEQ ID NO 32<1 nM >1000 nM >>1000 nM >1000x SEQ ID NO 34<10 nM >>1000 nM >>1000 nM >1000xSEQ ID NO 35<1 nM >1000 nM >>1000 nM >1000xSEQ ID NO 36<1 nM >1000 nM >>1000 nM >1000xSEQ ID NO 37<10 nM >>1000 nM >>1000 nM >1000x SEQ ID NO 38<10 nM >>1000 nM >>1000 nM >1000xSEQ ID NO 48<10 nM >1000 nM >>1000 nM >1000xSEQ ID NO 49<1 nM >100 nM >>1000 nM >1000xSEQ ID NO 50<1 nM >1000 nM >>1000 nM >1000x SEQ ID NO 51<1 nM >1000 nM >>1000 nM >1000xSEQ ID NO 52<1 nM >1000 nM >>1000 nM >1000xSEQ ID NO 53<10 nM >>1000 nM >>1000 nM >1000xSEQ ID NO 54<10 nM >>1000 nM >>1000 nM >1000x SEQ ID NO 55<10 nM >>1000 nM >>1000 nM >1000xSEQ ID NO 56<100 nM >>1000 nM >>1000 nM >100xKv1.3 selectivity was evaluated across a broadl p oafn ceompounds. For several of these, off-targetitv aityc was assessed at a representative concentrationst ag uapi to six potassium channels associated witehn ptioal side effects: Kv1.2, Kv1.1, Kv1.4, Kv1.5, KCa3.1, and1 K1v.1 (hERG). The compounds showed minimal inhibnit oiof these off-target channels, with significant acytiv oibt served only at very high concentrations. Iny m caanses, selectivityratios exceeded 10,000-fold—and in some instan ecveesn, 50,000-fold—over Kv1.3. These findings undoerresc theexceptional specificity of the compounds and sutg age losw risk of off-target pharmacological or sayfe liat bilities. A1,000-fold selectivity over Kv1.1 and Kv1.2 is jiufisetd because partial inhibition of these chann heals been linkedto adverse neurological effects in previous Kv1a.r3g-etting efforts. Higher selectivity levels—10,00 t0o- 50,000- fold—further minimize the risk of off-target acttiyv.i Such extreme selectivity is crucial to enabalefe s systemic or chronic administration without triggering side ecftfse. These results based on channel current iniohnibsit measured at certain selected concentrations allowing selecytiv eitstimations are shown in Table 5 along with steivlietyc assessments on reference compounds including thKeTx M1e3-2, KTX1 and AgTx3, which were template toxi unssedin designing the libraries from which highly Kv1 s.3elective compounds of the present invention wdeerent i fied. Thereference compounds also included Dalazatide, M,o skia-5144 described as selective compounds. The results (Table 4 and Table 5) show that allp co umnds of the present invention listed in Tablexh 4ib eitsuperior Kv1.3 selectivity compared to the referee cnocmpounds, which display less than 100-fold stievlietyc. Table 5 further demonstrates that several lead compo aucnhdiseved even more pronounced selectivity—excee 1d0in,0g00-and up to exceeding 50,000-fold—underscoring thgeh h sipecificity of this compound series for Kv1.3.Table 5. Potassium channel blocking test concentration ( / nM ef)ficacy (I%: mean±SEM, n=3-5), and selectiv oitfy compounds Kv1.3 Kv1.2 Kv1.1 Kv1.4 Kv1.5 KCa3.1 Kv11.1 Selectivity Compound (% inhi- (% inhi- (% inhi- (% inhi- (% inhi- (% inhi- (% inhi- (IC50Kv1.x / bition) bition) bition) bition) bition) bition) bition) IC50Kv1.3) SEQ ID NO 17 10 nM / 1000 nM / 1000 nM / ND ND ND ND >10,000 x 64±3% <10% <5% SEQ ID NO 20 10 nM / 88±2% 1000 nM / 1000 nM / ND ND ND ND >50,000 x 0.5 nM / <10% <5% 46±7% SEQ ID NO 22 1 nM / 55±3% 1000 nM / 1000 nM / 1000 nM / 1000 nM / 1000 nM / 1000 nM / >50,000x IC50 = <10% <10% <10% <10% <10% <10% 830 pM SEQ ID NO 30 1 nM / 1000 nM / 1000 nM / ND ND ND ND >10,000 x 57±6% 18±1% <5% SEQ ID NO 34 1 nM / 1000 nM / 1000 nM / ND ND ND ND >10,000 x 29±3% <10% <5% SEQ ID NO 35 1 nM / 1000 nM / 1000 nM / ND ND ND ND >100,000 x 76±4% <10% <5% SEQ ID NO 36 nM / 1000 nM / 1000 nM / ND ND ND ND >100,000 x 56±3% 12±1% <5% SEQ ID NO 37 1 nM / 1000 nM / 1000 nM / ND ND ND ND >10,000 x 46±3% <10% <5% SEQ ID NO 38 1 nM / 1000 nM / 1000 nM / ND ND ND ND >10,000 x 29±5% <10% <5% SEQ ID NO 48 0.5 nM / 1000 nM / 1000 nM / ND ND ND ND >10,000 x 41±1% 20±2% <5% SEQ ID NO 49 1 nM / 90±4% 1000 nM / 1000 nM / 55 nM / 55 nM / 55 nM / 55 nM / >10,000 x IC50 = 61±4% <10% <10% <10% <10% <10% 55 pM SEQ ID NO 50 1 nM / 85±4% 1000 nM / 1000 ND ND ND ND >50,000 x IC50 = 31±8% nM / <5% 31 pM SEQ ID NO 51 1 nM / 72±2% 1000 nM / 1000 nM / ND ND ND ND >50,000 x IC50 = 17±1% <5% 250 pM SEQ ID NO 52 1 nM / 1000 71±11% 1000 nM / <10 ND ND ND ND >100,000 x IC50 = nM / <5% % 31 pM SEQ ID NO 53 10 nM / 1000 nM / 1000 nM / ND ND ND ND >50,000 x 76±11% <10% <5% SEQ ID NO 54 1 nM / 1000 nM / 1000 nM / ND ND ND ND >100,000 x 42±3% <10% <5% SEQ ID NO 55 10 nM / 1000 nM / 1000 nM / ND ND ND ND >50,000 x 58±3% <10% <5% SEQ ID NO 57 1 nM / 95±2% 100 nM / 1000 nM / 100 nM / 100 nM / 100 nM / 100 nM / >50,000 x IC50 = 9±2% <10% <10% <10% 11±3% <10% 21 pM KTX1 1nM / 10 nM / ND ND ND ND ND <10x 68% 87% AgTx3 1 nM / 1000 nM / 10 nM / ND ND ND ND <100x 70% 33% 42% MeKTx13-2 100 nM / 1000 nM / 1000 nM / ND ND ND ND <10x 40% <10% 58% Dalazatide 0.07 nM* / 1 nM / ND ND ND ND ND <20x 82% 89% si-544 1 nM / 1000 nM / 100 nM / ND ND ND ND ~100x 46±4% <10% 43±5% Moka1 1 nM / 1000 nM / 1000 nM / ND ND ND ND <50x 12±1% 62±1% <10% *: the test concentration was equal to a publis IhCe5d0 value [Pennington M.W. et al., 2009] Dose-response curves on the Kv1.3 channel were m aelsaosured for five lead compounds (SEQ ID NO: 292,, 4 50, 51, 52, and 57), as shown in Figure 3. EXAMPLE 7: Testing serum stability of miniproteins Human serum stability of SEQ ID NO: 22 and itsv daetriives and truncated versions (SEQ ID NO: 52, 49, 51, 5570), were assessed and compared with that of Dalazatide. Human serum was obtained from Sigma (Cat no: S7502 m3l-). Compounds were dissolved in PBS (Gibco,cat. no: 10010-031) at 1mg / ml concentration anudte ddil further with ice-cold serum in 1:3 ratio tohi aecve 0.25mg / ml concentration. Of these mixtures, pairs of 200a-µmlp sles were aliquoted into separate low proteindi bnign tubes. Thenumber of pairs was equal to the number of stayb diluitration endpoints. Half of the aliquoted samp wles re frozenimmediately, stored at 80°C and used as contro sla (tm0ples), while the other half of the samples w inecreubated at 37°C until the stability endpoints (1, 2 and 3 d)a.y Asfter the given time of incubation frozen conltr soamples andsamples incubated at 37°C were precipitated byn agd 9d0i % acetonitrile 10% water +0.2% TFA buffer i:n1 1 ratio.The mixture was vortexed, cooled on ice for 15 m, i vnosrtexed again, then centrifuged at 13,000g f0or m 1ins.Supernatants were analyzed by Jasco HPLC systenmg u Tseiknokroma Europa Peptide C18 column and grat dienelution of Buffer A (H2O +0,1% trifluoroacetic acid) and Buffer B (90%t aocneitrile, 10% H2O +0.1% trifluoroacetic acid). Stability was calculated by the ratio of tAhUeC of the stability tested samples versus the A oUfC controlsamples. Figure 3 shows that after 72 hours ofb iantcioun, >80% of the tested compounds (SEQ ID NO,: 522 , 49,51, 50) are still intact, while Dalazatide almoostm cpletely degrades within 24 hours. In conclusi tohne, examinedminiproteins of present invention in contrast tola Dza tide show exceptional stability in human ser wuhmich is acritical advantage in therapeutic applications. . EXAMPLE 8: Testing the effects of Kv1.3 blockers in T cell activation assays in vitro Isolated human effector memory T (Tem) cells wesre d u to assess the efficacy of SEQ ID NO: 22, 4,95, 051compared with that of Dalazatide (Figure 5, Fig 6u)r.e This method involves stimulating the Tem ce wliltsh anti-CD3 antibodies and subsequently assessing T-cell aticotniv bay measuring the expression of activation merasrk (CD25 and CD40L) with and without the presence of Kv1.3 inithoibrs. Peripheral blood mononuclear cells (PBMCs) werela itseod by standard Ficoll-Paque density gradient centrifugation from buffy coats purchased from H thuengarian National Blood Transfusion Service. Teemlls c were isolated from PBMCs by magnetic separation usineg h tuhman CD4+ Tem cell isolation kit from Miltenyio Btec, according to the manufacturers’ instructions. Plate-bound anti-CD3 (BioLegend, clone OKT-3) wasesd u to stimulate Tem cells.96-well plates werete cdoa with 0.5 µg / well anti-CD3 antibody in 50 microlit PerBS (Gibco) for 2 hours at 37°C. Tem cells (2*10 c^e5ll / well in200 µL medium) were preincubate ed with the tebsst t saunces for 30 minutes at the targeted test cotrnactieon in anuncoated plate. The cell culture medium comprisePdM RI-1640 medium (Sigma) supplemented with GlutamI,ax-10% fetal bovine serum and 1% penicillin / streptomin.y Acfter the preincubation, the medium contain tihneg cells andthe test substance were transferred onto anti-CoDa3te-cd 96-well plates and activated for 24 hour 3s7 a°Ct in a 5%CO2 incubator. After 24 hours, the cell surfacer ex spsion of activation markers was visualized byub inaction withfluorescently labelled anti-CD25-PE and anti-CD4F0ILT-C antibodies (BioLegend) for 30 minutes at 4E °Cff.ect of Kv1.3 blockers on activation marker expression q,u aasntified by median fluorescent intensity (MFI)a,s w measured by flow cytometry using a MACSQuant® 10 Analyzer. In the first experiment, all the test substancerse w aepplied at a concentration of 50 nM (Figure A 5c)t.ivationmarker expression intensities in presence of intohrisbi were compared to CD3 stimulus control with toeust substancetreatment. Statistical Analysis: One-Way ANOVA foowlled by Dunnett’s post-hoc test comparing to thimeu sltated control. Data are presented as mean+SD of n=3le pla mraelasurements. **** indicates statistical sigicnaifnce with p < 0.0001. The results show that the expression ocef l Tl-specific activation markers CD25 (IL-2Ra) a CndD40L (CD154) was significantly inhibited by all applie todxin analogues with no significant difference orbvseed between them. The biological significance of these findin isgs that the suppressed activation state, eviden bcyed ecreasedCD25 expression on CD4+ Tem cells, leads to redu incted rleukin-2 binding, proliferation, and cellul eaxrpansion.Additionally, the lower expression of CD40L resu inlts an impaired capacity to bind to CD40 on thefa scuer of antigen-presenting cells (APCs). This interaction is crul c foiar APC activation, so its inhibition leads toc dre ased cytokineproduction and a less intensive immune response. In the second experiment, concentration-responlasetio rneship of the Kv1.3 channel blocker SEQ ID N 2O2: on T cell activation was also investigated. Thet c teosmpound was applied in a concentration rang 0e.1 o6f-100 nM before CD3 (OKT3) stimulus. Activation states aftfe drient concentrations were compared to CD3 stimsu clountrol without peptide treatment. The results sh ao cwoncentration-dependent inhibition of T cell-spfiecc aictivation marker expression by SEQ ID NO: 22, which was statistyic sailglnificant already at the lowest test conceniotnra otf 0.16 nM (Figure 6). Statistical Analysis: One-Way ANOVAl foowl ed by Dunnett’s post-hoc test comparing to tthimeu slated control. Data are presented as mean+SD of n=3le pla mraelasurements. Statistical significance **p<0;. *0*1** p < 0.0001. The effective inhibition of CD4+ Tem cells at lowon ccentrations underscores the high potency ofo txhien tanalogue. This potent inhibition indicates thatn ev aet lower concentrations, the toxin analogue cigan if sicantlyreduce interleukin-2 binding and proliferation d tuoe lower CD25 expression, as well as impair ther iancttion with antigen-presenting cells through reduced CD40L e esxspiorn, leading to decreased cytokine productiodn an diminished immune response. EXAMPLE 9: Testing effect of Kv1.3 inhibitors in the T cell cytokine release assay Inhibitory effect of SEQ ID NO: 22 on T-cell funoctni was tested and compared to Dalazatide in al T cel cytokine release assay as well. This approach e aspp alictivating Tem cells on anti-CD3-coated 96-w pelalltesantibodies as and measuring the subsequent re olef a inste rferon-gamma (IFNγ-), as shown in Figure 7.Supernatants of Tem cells after 48 hours of aciotivna wt ere collected and measured with the IγFN D-uoSet ELISA Kit from R&D Systems according to the manutufarcers’ instructions with minor modifications. Bfrliye, 96- well Nunc Maxisorp plates were coated with 2 µg / amnLti-IFN-γ capture antibody in 100 µl PBS (Gibco) per well at4°C, overnight. Next day, plates were washed th timree s with 250 µl PBS supplemented with 0.05% (v T / wv)een-20(PBST). Plates were blocked with 250 µl PBS plus (m 1% / v) bovine serum albumin (BSA) per well for 1u hro at room temperature (RT). After washing three times withS PTB, 80 µl of cell culture supernatant or IFγN s-tandard (2-folddilution calibrating series from 2500 to 39 pg / m wLe)re measured into the wells and plates incubaotred 2 f hours atRT. After three times washing, 200 ng / mL biotinyeldat anti-IFN-γ antibody in 1% (m / v) BSA-PBS was measured into each well in a volume of 100 µl for 1 hour. Aftears whing, HRP-conjugated streptavidin in 1:40 dilnut wioas added for 20 minutes. Plates were developed by additifo 1n0 o0 µl per well TMB solution (Thermo Fisher). Rcetioan was stopped with 1N HCl. Optical density of each wealls w measured immediately using a SpectraMax iD3o mpliactrereader set to 450 nm with wavelength correction 62 o0f nm. Secreted IFNγ- levels were calculated and plotted inGraphPad Prism using standard curves to interpo (slaetceond order polynomial / quadratic / ). Both Kv1.3 channel targeting peptides were app alite 5d0 nM concentration for 30 minutes before anrdin dgu the CD3 (OKT3) stimulus. Inhibition was compared C toD3 stimulus control without peptide treatment.ta Da re illustrated as mean ± SD of n=4 parallel measuretsm.e Sntatistical Analysis: One-Way ANOVA with Dunnt’set post- hoc test. ns p>0.05; *** p < 0.001; **** p < 0.000.1 As shown in Figure 7, SEQ ID NO: 22 inhibited I-FγN secretion of Tem cells similarly to Dalazatide, supportinge t chritical role of Kv1.3 inhibition in modulatingc Tell function. EXAMPLE 10: Long-term effect of Kv1.3 inhibitors in the T cell cytokine release assay after inhibitor removal We also wanted to test if our inhibitors are abole bl tock T cell functions for a week even after aor sth exposure time, supporting once-a-week dosage of the pat.ients Long-term inhibitory effect of SEQ ID 49, 50, 57)er we compared to si-544 in a T cell cytokine rele aassseay as well. This approach applied Kv1.3 channel inthoirbsi at 25 nM for 4 hours, followed by removal an 4d-day resting period. After resting, Tem cells were stimulated a onnti-CD3-coated plates for 72 hours, and IγFN le-vels in the supernatants were measured using a DuoSet ELISAD (R S&ystems). Inhibition was compared to CD3-stimeudlat control without peptide treatment. Data represeenatn m ± SD (n=4); statistical analysis was perform useidng one-wayANOVA with Dunnett’s post hoc test (ns p > 0.05;* * p* < 0.001; **** p < 0.0001). As shown in Figure, 8 SEQ IDNO: 49, 50, and 57 significantly inhibited IFγN- secretion, in contrast to si-544, supporting thuesta sined immunomodulatory effect of Kv1.3 inhibition. Supeartannts of Tem cells after 72 hours of activationre w ceollected and measured with the IFγN- DuoSet ELISA Kit from R&D Systems according to t mheanufacturers’ instructions with minor modifications. Briefly, 96-well Nunc Maisxorp plates were coated with μ 2g / mL anti-IFN-γ capture antibody in 100 μl PBS (Gibco) per well at 4°C, overnight. Next d palya,tes were washed three times with 2 μ5l P0BSsupplemented with 0.05% (v / v) Tween-20 30 (PBSTla).te Ps were blocked with 25 μ0l PBS plus 1% (m / v) bovineserum albumin (BSA) per well for 1 hour at roomp teemrature (RT). After washing three times with PBS 80T, μl of cell culture supernatant or IFγN s-tandard (2-fold dilution calibrating series fro 2m500 to 39 pg / mL) were measured into the wells and plates incubated for 2 hour RsT a.t After three times washing, 200 ng / mL biotinyeldat anti-IFN-γ antibody in 1% (m / v) BSA-PBS was measured into e waeclhl in a volume of 100 μl for 1 hour. After washing, HRP- conjugated streptavidin in 1:40 dilution was add35ed for 20 minutes. Plates were developed by adnd oitifo 100 μl per well TMB solution (Thermo Fisher). Reaction wasp spteod with 1N HCl. Optical density of each well w maesasuredimmediately using a SpectraMax iD3 microplate rera sdeet to 450 nm with wavelength correction of 62m0. n SecretedIFN-γ levels were calculated and plotted in GraphPadsm Pr uising standard curves to interpolate (seconder ord polynomial / quadratic / ). EXAMPLE 11: Pharmacokinetic evaluation of selective Kv1.3 inhibitor peptides Further to the serum stability assessment of Exeam 6p,l a pharmacokinetic (PK) study was performed to evaluate pharmacokinetics of a structurally rela ftaemdily of selective Kv1.3 inhibitor peptides fowlloing a single subcutaneous dose of 1 mg / kg in male rats and croem topa published results for Dalazatide (Tarchal. e,t 2 a012). In-life phase: Briefly, test items were formulated in physiologlic saaline and administered to the rats subcutaneously at a dosing volume of 1 mL / kg. Bl wooads collected at the following time points usin2g-E KDTA as anticoagulant: 5m, 15m, 30m, 1h, 2h and 4h. Thep sleasm were collected from 4 animals / group at eamchep tioint. The plasma was separated and stored in an ultra-fre (beezleorw -70°C) until analysis. Bioanalytics: For quantification of the peptides in rat plasm rael aiable LC / MS / MS method was developed. Reference standard of the analytes was provide VdR bGyT (test item peptides). The blank rat K2-EDTAas pml a wascollected from healthy drug-free rats and stored a i dneep-freezer when not in use. The concentra ratinogne of thecalibration curve was 1 ng / ml - 50 ng / ml. The low limerit of quantification was 1 ng / ml. For unknowanm sples plasma concentrations were calculated and results werend reodu to 3 valuable digits. In case plasma concteionntrsa wereoutside the range of the calibration curve thea lrin re lationship was extrapolated. Mean plasma cnotnracteions areshown in Figure 9. PK analysis: Maximal plasma concentrationsm (aCx) and time to maximal plasma concentrationmsax) (t were determined based on the observed highest averagsmea pl concentrations. AUlaCstvalues were calculated using thetrapezoidal method. Peak concentrations of all it te msts occurred at 0.25h - 0.5h after administrna.t Tiohe absorptionand elimination of all test items were rapid wibthso arption and elimination half-lives between 6-1n5d a 45-60 minutes,respectively. The pharmacokinetic parameters (claatlecdu by non-compartmental analysis) are showna ibnle T 6. From a PK perspective all tested peptides are dlikrueg m- olecules with high exposure and maximal plasm concentration. All peptides were absorbed rapi wdlhyi,le the elimination rate was in agreement witeh r tehnal excretion observed for high solubility and low volume of driibsuttion compounds (e.g. inulin) in rat Ps.lasma concentrations and PK parameters were also compared to publisahtead fo dr Dalazatide and its metabolite (Tarcha. e,t 2 a0l12). Based on tmax values the absorption of the novel peptides wamse swohat slower than for Dalazatide, while the eliamtiionn rate was almost an order of magnitude lowemra.xC and AUC values of the new peptides were 1-2 or odfe mrsagnitude higher compared to Dalazatide (Figure 8). Table 6: Mean pharmacokinetic parameters (n=4). Dose: 1kg m fgo / r each peptide s.c. PK parameters for Dalazatide and its metabolite were calculated ba osne tdhe plasma concentration taken from Tarchal., e 2t0 a12. SEQ ID SEQ ID SEQ ID SEQ ID SEQ ID SEQ ID Dalazatide Dalazatide NO: 22 NO: 52 NO: 51 NO: 49 NO: 50 NO: 57 metabolite AUC 25235.8 15335.8 24757.7 7199.5 15860.6 12330.1 5150. 309.5 (nM.min) Cmax(nM) 262.4 194.3 250.2 99.8 152.7 109.5 10.0 12.0 tmax(min) 30 30 30 15 15 15 5 5 ke(1 / min) 0.014 0.015 0.016 0.015 0.012 0.014 0.092 0.045 EXAMPLE 12: Effect of Kv1.3 blocker treatment in a rat delayed-type hypersensitivity (DTH) test in vivo The ability of the Kv1.3 blocker SEQ ID NO: 22 teod ruce oxazolone induced ear swelling, a DTH rena,ctio was investigated and compared with the respons veeh toicle and Dalazatide treatment. The experimenetsre w performed in female Sprague-Dawley rats (N=6 peorup g)r aged 10 weeks. Oxazolone (2 m / v% in 96% ethanol, 300 ml / animala))s w applied onto the shaved abdominal skin of roats t induce DTH (sensitization) on Day -6 and Day -5. d Oany 0, the rats were challenged by smearing 3 m0-L30 of 2%oxazolone solution onto both sides of the right. e Caorntrol (left) ears were treated with 96% etha ino al similarmanner. The test compounds (lyophilized powder)e w freershly dissolved in saline and injected subceuotaunsly at a dosing volume of 2 mL / kg on Day 0 before oxazolo chnaellenge. The ear thickness was measured withlip aer ca beforethe treatment on Day 0 and on Day 1, approxima 2te4ly hours after the challenge. Ear swelling wasu cla tlecd foreach animal as the difference in ear thicknessa oyn 1 D and Day 0 expressed in percentage of earn tehsicsk on Day 0. Oxazolone-treatment exerted an average of 80%w eeallrin sg in the control group treated with vehiclfete ar 24hours, while the thickness of the ethanol-treataerds e did not change significantly.As shown in Figure 10, both SEQ ID NO: 22 and Datliadze significantly suppressed ear swelling to l sairmi extent from 80% (vehicle control) to an average 47 o%f and 40%, respectively. These data indicate S thEaQt ID NO:22, as a representative member of the compo oufnd psresent invention demonstrates t ihne vivo effectiveness, expected for a Kv1.3 blocker. EXAMPLE 13: In silico immunogenicity assessment of Kv1.3 inhibitor peptides in humans The machine learning tool netMHCIIpan-4.3 was u tsoed predict the immunogenicity for a set of Kv1.3 inhibitors of the present invention an codmpetitor reference polypeptid (eTsable 7.). Developed at the University of Denmark (Nilsson, 2023), NetMHCIIpan-4.3 predictespt pide binding to HLA class II molecules using Aficrtiial Neural Networks (ANNs). The model was trained on ex atnensive dataset of over 650,000 measuremen Btisnd oifng Affinity (BA) and Eluted Ligand mass spectrometEryL (). The output of the model is a prediction score h foer l tikelihood of a peptide to be naturally presden btey an MHCII receptor of choice. The output includes %REaLn,k which normalizes the prediction score by cominpgar it to predictions of a set of random peptides. The pep itsid identified as a strong binder if it is founmdo ang the top 2% predicted peptides, while it is as a weak binde %rR ifankEL is above the threshold of the strong brisnd beut below10%. %RankEL scores above 10 indicate very weaekra inct ion between the peptide and the MCHII molec aunldeanticipate no antigen presentation and, there ifmorme,unogenicity. Allele subtypes were extendedl to ”M aSl covered” human HLA alleles and allele subtypes and %RankilEteLri fng was set to 20%. The number of identifietrdon sg and weak binding amino acid sequences for each pep atloidneg with the number of hits are reported. No immunogenic HLAII interactions were predictedr t fhoe lead sequences. Competitors si-544, OsK1[H],34A Moka1 and AgTx3 were predicted to be weakly immuennoicg. MeKTx132 contains a very immunogenic peptide fragment and is predicted be strongly immunogenic.Table 7. Number of strong binder (SB) and weak binder (W eBpi)topes in a representati sve t of highly selectiveKv1.3 inhibitors of the present invention and inrio vaus competitor reference polypeptides as asse bsysed netMHCIIpan-4.3. No. of SB No. of WB Protein (%RankEL <2) (2 < %RankEL < 10) SEQ ID NO 22 0 0 SEQ ID NO 34 0 0 SEQ ID NO 35 0 0 SEQ ID NO 36 0 0 SEQ ID NO 32 0 0 SEQ ID NO 30 0 0 SEQ ID NO 54 0 0 SEQ ID NO 57 0 0 SEQ ID NO: 92 (Moka1) 0 6 SEQ ID NO 59 (AgTx3) 0 17 SEQ ID NO 60 (MeKTx132) 1 25 SEQ ID NO 91 (si-544) 0 3 EXAMPLE 14: Secondary structure and fold predictions for the Kv1.3 inhibitor peptides All 47 protein sequences (SEQ ID NO:1 to 47) weerene grated into a FASTA file format. Multiple sequenc alignment (MSA) algorithm aligned the common reseisdu to consensus positions, like cystein residue psos initions 8, 14, 18, 28, 33, and 35. MSA tools for the analy inscisluded ClustalW [Larkin M.A. 2007] and MAFFT [Koaht K. et al, 2002] solutions. For secondary structure prediction, a locally extaebclue version of AlphaFold [Jumper J. et al, 20 w21a]s utilized. All 47-monomer protein structure predictions showedila srim outputs, which were analyzed using the Chim [Pereattersen E.F. et al., 2004] visualization program (Figure1s a 1nd 12). In designing these miniproteins, the presence olyf on three disulfide bonds—rather than the four commo fonulynd in related Kv1.3 inhibitors such as Vm24 a sni-d544— was a deliberate feature. This reduction simpli ofiexisdative folding, decreases the likelihood of p maiisred cysteineresidues, and improves chemical synthesis efficyie anc d yield. Importantly, three disulfide bridgeesr we found to besufficient for maintaining structural stability, wileh also contributing to improved solubility andd rueced aggregation, making these scaffolds well-suited for therape dueticvelopment. INDUSTRIAL APPLICABILTY The invention relates to potassium ion channelk belorsc having improved affinity and selectivity forv1 K.3 ion channel, and enhanced stability. The inhibitor compounds comprise a polypeptide conmepnt which is a miniprotein. the invention alsloat re sto therapeutic indications and diagnostic useshe of in thibitor compounds. The miniproteins retain their 3D fold, whereas m baey completed with additional fusion partners anodst phretic groups to adapt them to various uses in therapy d aiangdnostics. REFERENCES Altschul S. F., Gish, W., Miller, W., Myers, E. W L.i,pman D. J., Basic local alignment search to1o9l,9 (0) Journal of Molecular Biology, Volume 215, Issue 3, Page3s- 4010Ausubel F. M. et al., Short Protocols in Molecu Blaiorlogy: A Compendium of Methods from Current Prcootols in Molecular Biology, John Wiley & Sons, (1999) Short Protocols in Molleacru Biology, Chapter 18 Barman, P., Joshi, S., Sharma, S., Preet, S., Sah,a Sr.m, & Saini, A. (2023). Strategic approache ism tporovise peptide drugs as next generation therapeutics. Internalt jio unranal of peptide research and therapeutics4,) 2,96(1. doi:10.1007 / s10989-023-10524-3. Beeton, C., Wulff, H., Singh, S., Botsko, S., Crleoys,s G., Gutman, G. A., ... & Chandy, K. G. (200 A3) n.ovel fluorescent toxin to detect and investigate Kv1 c.h 3annel up-regulation in chronically activated T lymphocytes. Journal of Biological Chemistry, 2718)(,19928-9937. doi.org / 10.1074 / jbc.M212868200 Beeton, C., Wulff, H., Standifer, N. E., Azam, M P.u,llen, K. M., Pennington, M. W., ... & Chandy, K G.. (2006). Kv1. 3 channels are a therapeutic target for T-m cel dl iated autoimmune diseases. Proceedings of theNational Academy of Sciences, 103(46), 17414-174 d1o9i.o.rg / 10.1073 / pnas.060513610 Beeton, C., Wulff, H., Standifer, N.E., Azam, P.u,l Mlen, K.M., Pennington, M.W., et al. (2006). Kv1 c.h3annels are atherapeutic target for T cell-mediated autoimm duinse ases. Proceedings of the National Academyci oefn Scesof the USA, 103(44), 17414-17419. https: / / doi.o0rg.1 / 1073 / pnas.0605136103 Bielanska, J., Hernández-Losa, J., Pérez-Verdag Mu.e,r M,oline, T., Somoza, R., Ramón, Y., Cajal, C So.,ndom, E., Ferreres, J.C., Felipe, A. (2009). Voltage-depetnd peontassium channels Kv1.3 and Kv1.5 in human cra.nce Current Cancer Drug Targets, 9(8), 904-914. ht / tdposi:. / org / 10.2174 / 156800909790192400 Cañas, C.A., Castaño-Valencia, S., Castro-Herr Fe.ra (2,022). Pharmacological blockade of KV1.3 chaln anse a promising treatment in autoimmune diseases. Jour onfal Translational Autoimmunity, 5, 100146. https: / / doi.org / 10.1016 / j.jtauto.2022.100146 Castro, T.G., Melle-Franco, M., Sousa, C.E.A., Ccaov-Paaulo, A., Marcos, J.C. (2023). Non-Canonicalin Aom Acids as Building Blocks for Peptidomimetics: Structur Feu,nction, and Applications. Biomolecules, 13, 981. https: / / doi.org / 10.3390 / biom13060981 Chandy, K.G., Sanches, K., Norton, R.S. (2023)u.c Stutrre of the voltage-gated potassium channel K:V I1n.s3ights into the inactivated conformation and binding toer tahpeutic leads. Channels (Austin), 17(1), 2253104. https: / / doi.org / 10.1080 / 19336950.2023.2253104 Cheong, A., Li, J., Sukumar, P., Kumar, B., Zen.g,, R Fiches, K., Munsch, C., Wood, I.C., Porter, K,. BEe.ech, D.J. (2011). Potent suppression of vascular smooth meu cseclll migration and human neointimal hyperplasyia b KV1.3 channel blockers. Cardiovascular Researc(h2,) 8,9282-289. https: / / doi.org / 10.1093 / cvr / cvq305 Choi, B. H., & Hahn, S. J. (2010). Kv1. 3: a potiaeln pt harmacological target for diabetes. Acta Phaacromlogica Sinica, 31(9), 1031-1035. doi: 10.1038 / aps.2010..133 Cidad, P., Miguel-Velado, E., Ruiz-McDavitt, C.,o Anlso, E., Jiménez-Pérez, L., Asuaje, A., Carmon,a G Ya.rcía- Arribas D., López J., Marroquín Y., Fernández Mo.,q Rué M., Pérez-García M.T. & López-López, J. R.1 (52)0. Kv1. 3 channels modulate human vascular smoothl me u cseclls proliferation independently of mTOR sigina glpathway. Pflügers Archiv-European Journal of Phlyosgiyo, 467, 1711-1722. https: / / doi.org / 10.1007 / s040-42 014-1607-yComes, N., Bielanska, J., Vallejo-Gracia, A., Sneorr-aAlbarrás, A., Marruecos, L., Gómez, D., ... &lip Fe , A. (2013).The voltage-dependent K+ channels Kv1.3 and Kv i1n. h 5uman cancer. Frontiers in physiology, 4, 283.Fernández, I., Romi, R., Szendeffy, S., Martin-Ela iurec, M.F., Rochat, H., Van Rietschoten, J., Po Mn.s,, Giralt, E.(1994). Kaliotoxin (1–37) Shows Structural Diffecren s with Related Potassium Channel Blockers.Biochemistry, 33(47), 14256-14263. https: / / doi.o1r0g.1 / 021 / bi00251a038 Fung-Leung, W.P., Edwards, W., Liu, Y., Ngo, K.,g Asnana, J., Castro, G., Wu, N., Liu, X., SwansonV,., R. Wickenden, A.D. (2017). T Cell Subset and Stimuolnat Si trength-Dependent Modulation of T Cell Activoanti by Kv1.3 Blockers. PLoS One, 12(1), e0170102. h: / t / tdposi.org / 10.1371 / journal.pone.0170102 Garcia, M.L., Garcia-Calvo, M., Hidalgo, P., Lee.,, A Mackinnon, R. (2000). Purification and Charaicztaetrion of Three Inhibitors of Voltage-Dependent K+ Chann Jeolsu.rnal of Biological Chemistry, 275(41), 6834-6.839 Ghorpade, R., & Kumar, M. S. (2022). Formulation p oefptides and peptidomimetics. In Peptide andd Poemptiimetic Therapeutics (pp.213-234). Academic Press. do / 1i.o0r.1g016 / B978-0-12-820141-1.00017-0. Hansen, L. K. (2014). The role of T cell potassi cuhmannels, KV1. 3 and KCa3. 1, in the inflammatoarysc cade in ulcerative colitis. Danish medical journal, 61(1 B1)4,946-B4946. . Hou, W., Zhang, X., Liu, C.F. (2017). Progress ihne Cmical Synthesis of Peptides and Proteins. Tratinosnasc of Tianjin University, 23, 401-419. https: / / doi.org / .1007 / s12209-017-0068-8Ibeanu, N., Egbu, R., Onyekuru, L., Javaheri, Hh.,aw K, P.T., Williams, G.R., Brocchini, S., Awwad, ( S2.020). Injectables and Depots to Prolong Drug Action ofote Pirns and Peptides. Pharmaceutics, 12(10), 999. https: / / doi.org / 10.3390 / pharmaceutics12100999 Immler, R., Nadolni, W., Bertsch, A., Morikis, V R.,ohwedder, I., Masgrau-Alsina, S., ... & Sperand Mio., (2022). The voltage-gated potassium channel KV1. 3 regsula nte utrophil recruitment during inflammation.Cardiovascular research, 118(5), 1289-1302. 10. / 1c0vr9 / 3cvab133 Jensen, K. J., Shelton, P. T., & Pedersen, S.d Ls.. ()E. (2013). Peptide synthesis and applicatio.n 2s5 (3p). New York: Humana Press. Jumper, J., Evans, R., Pritzel, A., Green, T., r Fnigouv, M., Ronneberger, O., ... & Hassabis, D. (2)0.2 H1ighly accurate protein structure prediction with AlphadF.o Nlature, 596(7873), 583-589. DOI: 10.1038 / s41052816- 03819-2Kamo, N., Hayashi, G., Okamoto, A. (2019). Chemi Scyanl thesis of Cys-Containing Protein via ChemostievlecDeprotection with Different Palladium Complexes. S AC Publications, Collection. https: / / doi.org / 10.1021 / acs.orglett.9b03152 Kappelmann-Fenzl, M. (Ed.). (2021). Next generati soenquencing and data analysis. Springer Internaaltion Publishing; doi.org / 10.1007 / 978-3-030-62490-3 Katoh, K., Misawa, K., Kuma, K. I., & Miyata, T.0 (202). MAFFT: a novel method for rapid multiple seqnuce alignment based on fast Fourier transform. Nucle aiccids research, 30(14), 3059-3066. doi.org / 10.1093 / nar / gkf436 Khanna, R., Roy, L., Zhu, X., & Schlichter, L. C2.0 (01). K+ channels and the microglial respiratouryrs bt. American Journal of Physiology-Cell Physiology, 280(4), C-7C98606. doi: 10.1152 / ajpcell.2001.280.4.C796. Khanna, R., Roy, L., Zhu, X., Schlichter, L.C. (210).0 K+ channels and the microglial respiratory bt.u Arsmerican Journal of Physiology - Cell Physiology, 280(4),9 C67-806. https: / / doi.org / 10.1152 / ajpcell.2001.28C07.49.6 Kundu-Raychaudhuri, S., Chen, Y. J., Wulff, H., &ay Rchaudhuri, S. P. (2014). Kv1. 3 in psoriatica dsisee: PAP-1, asmall molecule inhibitor of Kv1. 3 is effectivne t ihe SCID mouse psoriasis–xenograft model. Jou orfnalAutoimmunity, 55, 63-72. https: / / doi.org / 10.101j6a / uj.t.2014.07.003 Kuzmenkov, A.I., II, Peigneur S., Tytgat J., Vaesvssilki A.A. (2019). Pharmacological Characterisatio fn MeKTx13-2 and MeKTx13-3, Peptide Ligands of Potuamssi Channels From the Scorpion Mesobuthus eupeus Venom. Russ. J. Physiol., 105, 1452-1462. httposi:. / o / drg / 10.1134 / S0869813919110074Kuzmenkov, A.I., Vassilevski, A.A., Kudryashova,S K.,. Nekrasova, O.V., Peigneur, S., Tytgat, J.,a Fneo vf, A.V.,Kirpichnikov, M.P., Grishin, E.V. (2015). Variabtiyli of potassium channel blockers in Mesobuthus u esupe scorpion venom with focus on Kv1.1: An integratreadn tscriptomic and proteomic study. Journal of Bgioicloal Chemistry, 290(19), 12195-12209. https: / / doi.org.1 / 10074 / jbc.M115.637611 Lagreca E., Onesto V., Di Natale C., La Manna Se.,tti N PA., Vecchione R. (2020). Recent advanceshe in t formulation of PLGA microparticles for controlledru dg delivery. Prog Biomater., 9(4), 153-174. https: / / doi.org / 10.1007 / s40204-020-00139-y Larkin, M. A., Blackshields, G., Brown, N. P., Chnean, R., McGettigan, P. A., McWilliam, H., ... & Hgigins, D. G. (2007). Clustal W and Clustal X version 2.0. bioirnmfatics, 23(21), 2947-2948. doi: 10.1093 / bioinformatics / btm404. Legros, C., Pollmann, V., Knaus, H. G., Farrell, M A.., Darbon, H., Bougis, P. E., ... & Pongs, O.0 (02)0. Generating a high affinity scorpion toxin receptor in KcsA-K.v13 chimeric potassium channels. Journal of Bioclaolgi Chemistry, 275(22), 16918-16924. https: / / doi.org.1 / 10074 / jbc.275.22.16918 Lowinus, T., Bose, T., Simeoni, L., Schraven, Bo.,m Bmhardt, U. (2020). Kv1.3 Potassium Channels: Pisrionmg Therapeutic Targets in Hematological Malignanc Jie Cs.ell Signal, 1(3), 79-86.Matheu, M. P., Beeton, C., Garcia, A., Chi, V., Rga rnaju, S., Safrina, O., ... & Cahalan, M. D. (2)0.0 Im8 aging ofeffector memory T cells during a delayed-type hyspeenrsitivity reaction and suppression by Kv1. 3 cnhealn block. Immunity, 29(4), 602-614. doi: 10.1016 / j.imunmi.2008.07.015. Nair, A.B., Jacob, S. (2016). A simple practiced geu fior dose conversion between animals and hum Baans.i Jc Clin Pharm, 7(2), 27-31. https: / / doi.org / 10.4103 / 09760-50.177703Navarro-Pérez, M., Capera, J., Benavente-Garc,ia C,a As.sinelli, S., Colomer-Molera, M., & Felipe, ( A2.024). Kv1.3 in the spotlight for treating immune diseases. Ertxp Oepinion on Therapeutic Targets, 28(1–2), 67–82. doi.org / 10.1080 / 14728222.2024.2315021 Nikouee, A., Khabiri, M., & Cwiklik, L. (2015). Scropion toxins prefer salt solutions. Journal of mcoullear modeling, 21, 1-14. doi.org / 10.1007 / s00894-015-2822-y Nixon, A. E. (Ed.). (2014). Therapeutic peptidese.t Mhods and Protocols, Springer. Norton, R.S., Pennington, M.W., Wulff, H. (2004)o.t Passium channel blockade by the sea anemone S tohxKin for the treatment of multiple sclerosis and other amumtouine diseases. Curr Med Chem, 11(23), 3041-3052. https: / / doi.org / 10.2174 / 0929867043363947. Nugrahadi, P. P., Hinrichs, W. L., Frijlink, H. W S.,chöneich, C., & Avanti, C. (2023). Designing fourlmation strategies for enhanced stability of therapeutipcti pde s in aqueous solutions: A review. Pharmacse,u 1ti5c(3),935. doi: 10.3390 / pharmaceutics15030935. Olsen, C., Lustig, K., Iadonato, S., Tarcha, E. G,u &ttman-Yassky, E. (2017).695 Topical applicat oiofn KPI-150, a potent inhibitor of Kv1. 3 channels on effector moermy T cells, demonstrates preclinical efficacy itnop aic dermatitis model. Journal of Investigative Dermoagtoyl, 137(5), S119. doi.org / 10.1016 / j.jid.2017.028.71 Panyi, G., Varga, Z., Gaspar, R. (2004). Ion Chalsn anned Lymphocyte Activation. Immunol Lett, 92, 5665-. Pechmann, S., Frydman, J. (2014). Interplay betw ceheanperones and protein disorder promotes the t eiovnolu of protein networks. PLoS Comput Biol, 10(6), e1003.6 h7t4tps: / / doi.org / 10.1371 / journal.pcbi.1003674. Pennington, M.W., Beeton, C., Galea, C.A., Smith.J,., B Chi, V., Monaghan, K.P., Garcia, A., Ranga,ra Sju., Giuffrida, A., Plank, D., Crossley, G., Nugent, DK.h,aytin, I., Lefievre, Y., Peshenko, I., Dixon,, C. hauhan, S., Orzel, A., Inoue, T., Hu, X., Moore, R.V., Nonrt, R.S., Chandy, K.G. (2009). Engineering a stab nlde selective peptide blocker of the Kv1.3 channel in ly Tmphocytes. Mol Pharmacol, 75(4), 762-773. https: / / doi.org / 10.1124 / mol.108.052704 Pérez-García, M. T., Cidad, P., & López-López, . J. (2 R018). The secret life of ion channels: Kv1.o 3ta pssium channels and proliferation. American Journal of s Piohlyogy-Cell Physiology, 314(1), C27-C42. https: / / doi.org / 10.1152 / ajpcell.00136.2017 Pettersen, E. F., Goddard, T. D., Huang, C. C.,c Ch,o Gu. S., Greenblatt, D. M., Meng, E. C., & Fe,rr Tin. E. (2004). UCSF Chimera—a visualization system for explorato rerysearch and analysis. Journal of computational chemistry, 25(13), 1605-1612. doi: 10.1002 / jcc.240.0 P8MID: 15264254. Rangaraju, S., Gearing, M., Jin, L. W., & Levey, ( A2.015). Potassium channel Kv1. 3 is highly expereds bsy microglia in human Alzheimer's disease. Journa Al l ozfheimer's disease, 44(3), 797-808. doi: 10.32A3D3 / -J 141704. Rockville, MD: US Food and Drug Administration; (0250). Guidance for Industry: Estimating the Maximu Smafe Starting Dose in Adult Healthy Volunteer. Rudy, B. (1988). Diversity and ubiquity of K chanlsn.e Neuroscience, 25(3), 729-749. doi.org / 10.1031066 / 0- 4522(88)90033-4. Serrano-Albarrás, A., Estadella, I., Cirera-Roco Ssa.,, Navarro-Pérez, M., & Felipe, A. (2018). Kv1:. a 3 multifunctional channel with many pathological imicpaltions. Expert opinion on therapeutic targets(2, 2),2101- 105. doi.org / 10.1080 / 14728222.2017.1420170 Sharonov, G. V., Nekrasova, O. V., Kudryashova, S K.,. Kirpichnikov, M. P., & Feofanov, A. V. (2021). Bioengineered System for High Throughput Screen oifn Kgv1 Ion Channel Blockers. Bioengineering, 8(11), 187. https: / / doi.org / 10.3390 / bioengineering8110187 Szekér, P., Bodó, T., Klima, K., Csóti, Á., Hanh.,N N., Murányi, J., Hajdara, A., Szántó, T.G., Pan Gy.i,, Megyeri, M., Péterfi, Z., Farkas, S., Gyöngyösi, N., Horn,y Pák. (2024). KcsA-Kv1.x chimeras with complete n ligda binding sites provide improved predictivity for e scerning selective Kv1.x blockers. Journal of Biocloagli Chemistry. https: / / doi.org / 10.1016 / j.jbc.2024.105715 Takacs, Z., Toups, M., Kollewe, A., Johnson, E.e,l Clou, L.G., Driessens, G., Biancalana, M., Koide.,, P Aonte, C.G., Perozo, E., Gajewski, T.F., Suarez-Kurtz, G., Ko, i Sd.e, Goldstein, S.A.N. (2009). A designer liganpdec sific for Kv1.3 channels from a scorpion neurotoxin-ba lsiberdary. Proceedings of the National Academy oife Snc esof the USA, 106(52), 22211-22216. https: / / doi.o0rg.1 / 1073 / pnas.0910123106 Takeuchi, I., Tomoda, T., Hamano, A., Makino, K0.1 (27). Effects of physicochemical properties of p(loalcytide-co- glycolide) on drug release behavior of hydropho dbricug-loaded nanoparticles. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 520, 77781.- h7ttps: / / doi.org / 10.1016 / j.colsurfa.2017.02.054 Tarcha, E.J., Chi, V., Muñoz-Elías, E.J., Bailey.,, L Dondono, L.M., Upadhyay, S.K., Norton, K., Ban, k As., Tjong, I., Nguyen, H., Hu, X., Ruppert, G.W., Boley, S. SEl.a,uter, R., Sams, J., Knapp, B., Kentala, D.,s Heann, Z., Pennington, M.W., et al. (2012). Durable pharmagcioclaol responses from the peptide ShK-186, a spcecifi Kv1.3 channel inhibitor that suppresses T cell mateodris of autoimmune disease. Journal of Pharmayco alnodg Experimental Therapeutics, 342(3), 642-653. ht / tdposi:. / org / 10.1124 / jpet.112.191890 Tarcha, E.J., Olsen, C.M., Probst, P., Peckham M, Du.ñ,oz-Elías, E.J., Kruger, J.G., Iadonato, S.P0.17 (2). Safety and pharmacodynamics of dalazatide, a Kv1.3 cha innnheiblitor, in the treatment of plaque psoriasis: A randomized phase 1b trial. PLoS ONE, 12(7), e0128.0 h7t6tps: / / doi.org / 10.1371 / journal.pone.0180762 Tyagi, A., Ahmed, T., Jian, S., Bajaj, S., Ong,. S, . GToay, S.S.M., Zhao, Y., Vorobyov, I., Tian, C. h,andy, K.G., Bhushan, S. (2022). Rearrangement of a unique K sve1l.e3ctivity filter conformation upon binding of d arug. Proceedings of the National Academy of Sciences t ohfe USA, 119(5), e2113536119. https: / / doi.org / 10.1073 / pnas.2113536119Varga, Z., Gurrola-Briones, G., Papp, F., Rodríg duez la Vega, R.C., Pedraza-Alva, G., Tajhya, R G.Ba.s,par, R.,Cardenas, L., Rosenstein, Y., Beeton, C., Pos Ls.aDn.i,, Panyi, G. (2012). Vm24, a natural immunosuepspsrive peptide, potently and selectively blocks Kv1.3 psosituam channels of human T cells. Molecular Pharmloagcyo, 82(3), 372-382. https: / / doi.org / 10.1124 / mol.112.00768 Varga, Z., Tajti, G., & Panyi, G. (2021). The Kv 31. K+ channel in the immune system and its “precnisio pharmacology” using peptide toxins. Biologia fut,u 7ra2, 75-83. https: / / doi.org / 10.1007 / s42977-0217-010-07 Visan, V., Fajloun, Z., Sabatier, J.M., Grissme.r (,2 S004). Mapping of maurotoxin binding sites onv h1K.2, hKv1.3, and hIKCa1 channels. Molecular Pharmacology, 661(150),3-1112. https: / / doi.org / 10.1124 / mol.104.002774 Wang, T., Lee, M.H., Johnson, T., Allie, R., Hu, LC.alabresi, P.A., Nath, A. (2010). Activated T-lsce inl hibit neurogenesis by releasing granzyme B: rescue by.3 K bvl1ockers. Journal of Neuroscience, 30, 5020-.50.27 doi: 10.1523 / JNEUROSCI.0311-10.2010Wang, X., Li, G., Guo, J., Zhang, Z., Zhang, S.u, , Z Yh., ... & Tao, J. (2020). Kv1. 3 channel as ay k theerapeutictarget for neuroinflammatory diseases: state of a trhte and beyond. Frontiers in neuroscience, 133,.13d9oi: 10.3389 / fnins.2020.00163. Winkler, D.F. (2020). Automated Solid-Phase Pept Sidyenthesis. Methods in Molecular Biology, 2103,9549.- https: / / doi.org / 10.1007 / 978-1-0716-0227-0_5 Winkler, D.F., Tian, K. (2015). Investigation ofe th automated solid-phase synthesis of a 38mer pee wptitidh difficult sequence pattern under different synthesis streast.egi Amino Acids, 47(4), 787-794. https: / / doi.org / 10.1007 / s00726-014-1909-6 Wulff, H., Calabresi, P. A., Allie, R., Yun, S.,n Pneington, M., Beeton, C., & Chandy, K. G. (2003h).e T voltage- gated Kv1.3 K+ channel in effector memory T cealsls new target for MS. The Journal of Clinical Intvigeastion, 111(11), 1703-1713. https: / / doi.org / 10.1172 / jci11692 Wulff, H., Castle, N. A., & Pardo, L. A. (2009). Vltaoge-gated potassium channels as therapeuticts ta.r Ngeature Reviews Drug Discovery, 8(12), 982-1001. https:i / . / odrog / 10.1038 / nrd2983 Xu, J., Koni, P.A., Wang, P., Li, G., Kaczmarek,, W L.u, Y., Li, Y., Flavell, R.A., Desir, G.V. (200.3 T)he voltage- gated potassium channel Kv1.3 regulates energyo hsotmaseis and body weight. Human Molecular Genetics, 12(5), 551-559. https: / / doi.org / 10.1093 / hmg / ddg049 Xu, J., Wang, P., Li, Y., Li, G., Kaczmarek, L. K W.,u, Y., ... & Desir, G. V. (2004). The voltage-egdat potassium channel Kv1. 3 regulates peripheral insulin sevnistyit.i Proceedings of the National Academy of Sceiesn,c 101(9), 3112-3117. doi: 10.1073 / pnas.0308450100. Zayas-Arrabal, J., Alquiza, A., Rodríguez-de-Yur Are.,, Echeazarra, L., Fernández-López, V., Galle Mg.o,, & Casis, O. (2021). Kv1.3 channel blockade improves inflaamtomry profile, reduces cardiac electrical remodge,li annd prevents arrhythmia in type 2 diabetic rats. Cavradsiocular Drugs and Therapy, 1-11. https: / / doi.org / 10.1007 / s10557-021-07264-1 Zheng, J.S., Tang, S., Qi, Y.K., et al. (2013).m Chiceal synthesis of proteins using peptide hydraszi adse thioester surrogates. Nature Protocols, 8, 2483–2495. h / tdtposi.:o / rg / 10.1038 / nprot.2013.152

Claims

CLAIMS 1. A Kv1.3 potassium channel inhibitor compound, coimsinpgr a Kv1.3 inhibitor polypeptide component, wherein said polypeptide component comprises three diseul bfirdidges and said polypeptide component comprises the follow ainmgino acid sequence of formula (1) or a sequence comprising at most 1 or 2 or 3 further mutationrse,fe prably at most 1 or 2 or 3 conservative replaecnetms: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 X X X X X X X C X X S X X C X X X C K E A G X X X G K C X N X K C X C X X X(1)(SEQ ID NO: 63); wherein, independently, X1 is any proteinogenic amino acid, or a non-proteinogenic amino acid selected from the group consisting of Nle, sarcosine (MeGly), 2,3-diaminopropionic acDidp (r), 2,4-diaminobutyric acid (Dbu), Orn, homo-lnyesi (hLys), Nva, Abu, Aib, homo-glutamine (hGln), beta-hydroxynolrinvae (β-OH-Nva), 3-iodo-tyrosine (3I- Tyr), citrulline, pipecolic acid (Pip), azetidine--c2arboxylic acid (Aze), and a Phe derivative; or a deletion; X2is any proteinogenic amino acid, or a non-proteinogenic amino acid selected from the group consisting of Nle, sarcosine (MeGly), 2,3-diaminopropionic acDidp (r), 2,4-diaminobutyric acid (Dbu), Orn, homo-lnyesi (hLys), Nva, Abu, Aib, homo-glutamine (hGln), beta-hydroxynolrinvae (β-OH-Nva), 3-iodo-tyrosine (3I- Tyr), citrulline, pipecolic acid (Pip) or azetidine-2-carboxylicd ac (Ai ze), and a Phe derivative or a deletion; X3 is any proteinogenic amino acid, or a non-proteinogenic amino acid selected from the group consisting of Nle, sarcosine (MeGly), 2,3-diaminopropionic acDidp (r), 2,4-diaminobutyric acid (Dbu), Orn, homo-lnyesi (hLys), Nva, Abu, Aib, homo-glutamine (hGln), beta-hydroxynolrinvae (β-OH-Nva), 3-iodo-tyrosine (3I- Tyr), citrulline, pipecolic acid (Pip), azetidine--c2arboxylic acid (Aze), and a Phe derivative; or a deletion; X4 is any proteinogenic amino acid, or a non-proteinogenic amino acid selected from the group consisting of Nle, sarcosine (MeGly), 2,3-diaminopropionic acDidp (r), 2,4-diaminobutyric acid (Dbu), Orn, homo-lnyesi (hLys), Nva, Abu, Aib, homo-glutamine (hGln), beta-hydroxynolrinvae (β-OH-Nva), 3-iodo-tyrosine (3I- Tyr), citrulline, pipecolic acid (Pip), azetidine-2-carboxylic ac (Aidze), and a Phe derivative; or a deletion; X5 is any proteinogenic amino acid, or a non-proteinogenic amino acid selected from the group consisting of Nle, sarcosine (MeGly), 2,3-diaminopropionic acDidp (r), 2,4-diaminobutyric acid (Dbu), Orn, homo-lnyesi (hLys), Nva, Abu, Aib, homo-glutamine (hGln), beta-hydroxynolrinvae (β-OH-Nva), 3-iodo-tyrosine (3I- Tyr), citrulline, pipecolic acid (Pip) or azetidine-2-carboxylicd ac (Ai ze), and a Phe derivative; or a deletion;X6 is a hydrophobic amino acid, an acidic amino a ocrid a basic amino acid, preferably selected from( V )a,lGlu(E) and Lys(K), respectively, or a non-proteinogenic amino acid selected from the group consisting of 2,3-diaminopropionic acid (Dpr), 2,4-diaminobuty aric id (Dbu), Orn, homo-lysine (hLys), N,v Aabu, Aiband homo-glutamine (hGln); or a deletion;X7is Pro(P), Lys(K), Glu(E) or Ser(S), or a non-proteinogenic amino acid selected from the group consisting of 2,3-diaminopropionic acid (Dpr), 2,4-diaminobuty aric id (Dbu), Orn, homo-lysine (hLys), homo-glutame in(hGln), pipecolic acid (Pip) or azetidine-2-carboxylic ac (Aidze) and Aib; or a deletion; or any one of X1to X7is a pyroglutamate (pGlu), provided that said p iGsl Nu-terminal, X9is Thr(T), Lys(K), or Ser(S), or a non-proteinogenic amino acid selected from the group consisting of beta-hydroxynorvalineβ (-OH-Nva), 2,3-diaminopropionic acid (Dpr), 2,4-diianmobutyric acid (Dbu), Orn, homo-lysine (hLys) and Aib; X10is Gly(G), His(H) or Ala(A), or a non-proteinogenic amino acid selected from the group consisting of sarcosine (MeGly), Abu and Aib; X12is Pro(P), Gly(G), Lys(K) or Arg(R), or a non-proteinogenic amino acid selected from the group consisting of sarcosine (MeGly), 2,3-diaminopropionic acid (Dp 2r,)4,-diaminobutyric acid (Dbu), Orn, homo-lysine (hLys), citrulline, pipecolic acid (Pip), azetidi-n2e-carboxylic acid (Aze); X13is Gln(Q), Asp(D), Glu(E) or Asn(N), preferablyn G(Ql ) or Asp(D); or homo-glutamine (hGln), X15is Leu(L), Lys(K) or Val(V), preferably Leu(L); or a non-proteinogenic amino acid selected from the group consisting of Nle, 2,3-diaminopropionic acid (Dpr), 2,4-diaminotybruic acid (Dbu), Orn, homo-lysine (hLys), N,v Aabu, Aib and homo-glutamine (hGln); X16is Gln(Q), Glu(E) or Lys(K), or a non-proteinogenic amino acid selected from the group consisting of 2,3-diaminopropionic acid (Dpr), 2,4-diaminobuty aric id (Dbu), Orn, homo-lysine (hLys) and homo-glutamine (hGln); X17is Ser(S), Lys(K) or Ala(A), or a non-proteinogenic amino acid selected from the group consisting of Abu, Aib, 2,3-diaminopropionic acid (Dpr), 2,4-diaminobuty aric id (Dbu), Orn, homo-lysine (hLys) andhomo-glutamine (hGln); X23is Met(M) or Nle; X24 is Arg(R) or Thr(T); or citrulline or beta-hydronxoyrvaline (β-OH-Nva); X25 is Tyr(Y) or Phe(F), or a non-proteinogenic amino acid selected from the group consisting-i oofd 3o-tyrosine (3I-Tyr) and a Phe derivative; X29 is Met(M) or Nle; X31 is Arg(R), Lys(K) or Gly(G), preferably Arg(R) o Grly(G); or a non-proteinogenic amino acid selected from the group consisting of citrulline, 2,3-diaminopropionic acid (Dpr), 2,4a-dmiinobutyric acid (Dbu), Orn, homo-lysine (hLys)d an sarcosine (MeGly);X34is Lys(K) or Arg(R), or a non-proteinogenic amino acid selected from the group consisting of 2,3-diaminopropionic acid (Dpr), 2,4-diaminobuty aric id (Dbu), Orn, homo-lysine (hLys) and citrull;ineX36 is Phe(F), Tyr(Y) or Ser(S), preferably Phe(F) T oyr (Y), more preferably Phe(F),or a non-proteinogenic amino acid selected from the group consistingi obf, A 3-iodo-tyrosine (3I-Tyr) and aPhe derivative, preferably a Phe derivative, X37is Gly(G), Ser(S) or Pro(P), preferably Gly(G) P orro(P), or a non-proteinogenic amino acid selected from the group consistinga orcfo ssine (MeGly), pipecolic acid sarcosine (MeGly), (Pip), azetidine-2-carboxylicid a (cAze), or a deletion; X38is Lys(K), Arg(R), or a hydrophobic amino acid, p inarticular Lys(K), Arg(R), or Ile(I), preferablyr Ag(R), or a non-proteinogenic amino acid selected from the group consisting of 2,3-diaminopropionic acid (Dpr), 2,4-diaminobuty aric id (Dbu), Orn, homo-lysine (hLys), citrulline,va Nand Nle, preferably citrulline; or a deletion; wherein a Phe-derivative is selected from the gr coounpsisting of - 4-fluoro-phenylalanine, - 4-amino-phenylalanine, - 4-nitro-phenylalanine, - 4-methyl-phenylalanine; and wherein optionally any one of said amino acidsn is al apha-methyl amino acid, in particular at mos atm 5ino acids is / are alpha-methyl amino acid; wherein optionally any one of said amino acidso astit pions from 1 to 10, preferably 1 to 7 and 2124 to is an N-methyl amino acid, in particular at most 5 am aincoids is / are N-methyl amino acid; wherein optionally at most 5 amino acids selecrteodm f X1, X2, X3, X4, X5 is a D amino acid; or a salt thereof, andwherein said inhibitor compound is capable of steivlec ly inhibiting a Kv1.3 potassium channel prot.ein2. The potassium channel inhibitor compound accord toin cglaim 1, wherein said polypeptide component comprises the following amino acid sequence of fuolarm (1): 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 X X X X X X X C X X S X X C X X X C K E A G X X X G K C X N X K C X C X X X(1)(SEQ ID NO: 63); wherein, X1, X2, X3, X4 and X5 are each independently a pnryoteinogenic amino acid, or a non-proteinogenic amino acid selected from the group consisting of Nle, sarceos (MineGly), 2,3-diaminopropionic acid (Dpr), 2,4- diaminobutyric acid (Dbu), Orn, homo-lysine (hLy Ns)v,a, Abu, Aib, homo-glutamine (hGln), beta- hydroxynorvalineβ (-OH-Nva), 3-iodo-tyrosine (3I-Tyr), citrulline, peipcolic acid (Pip), azetidine-2-carboxylic acid (Aze), and a Phe derivative, and a pyroglutaem (paGlu), provided that said pGlu is N-terminarl, a o deletion;X6 is a hydrophobic amino acid, an acidic amino a ocrid a basic amino acid, preferably selected from( V )a,lGlu(E) and Lys(K), respectively, or n aon-proteinogenic amino acid selected from the group consisting,3 o-f 2 diaminopropionic acid (Dpr), 2,4-diaminobutyricd ac (iDbu), Orn, homo-lysine (hLys), N,v Aabu, Aib, homo- glutamine (hGln), and a pyroglutamate (pGlu) proevdid that said pGlu is N-terminal; or d aeletion; X7 is Pro(P), Lys(K), Glu(E) or Ser(S), or n aon-proteinogenic amino acid selected from the group consisting of2,3-diaminopropionic acid (Dpr), 2,4-diaminobuty aric id (Dbu), Orn, homo-lysine (hLys), homo-glutame in(hGln), pipecolic acid (Pip) or azetidine-2-carboxylic ac (Aidze), Aib, and a pyroglutamate (pGlu) providedat th said pGlu is N-terminal; or d aeletion; X9 is Thr(T), Lys(K), or Ser(S), or n aon-proteinogenic amino acid selected from the group consistinge otaf- b hydroxynorvalineβ (-OH-Nva), 2,3-diaminopropionic acid (Dpr), 2,4-diianmobutyric acid (Dbu), Orn, homo- lysine (hLys) and Aib; X10is Gly(G), His(H) or Ala(A), or a non-proteinogenic amino acid selected from the group consisting of sarcosine (MeGly), Abu and Aib; X12is Pro(P), Gly(G), Lys(K) or Arg(R), or n aon-proteinogenic amino acid selected from the group consisting of sarcosine (MeGly), 2,3-diaminopropionic acid (rD),p 2,4-diaminobutyric acid (Dbu), Orn, homo-lysine (hLys), citrulline, pipecolic acid (Pip), azetidi-n2e-carboxylic acid (Aze); X13 is Gln(Q), Asp(D), Glu(E) or Asn(N), preferablyn G(Ql ) or Asp(D); or homo-glutamine (hGln), X15is Leu(L), Lys(K) or Val(V), preferably Leu(L); o ar non-proteinogenic amino acid selected from the group consisting of Nle, 2,3-diaminopropionic acid (Dp 2r,)4,-diaminobutyric acid (Dbu), Orn, homo-lysineLy (hs), Nva, Abu, Aib and homo-glutamine (hGln); X16 is Gln(Q), Glu(E) or Lys(K), or a non-proteinogenic amino acid selected from the group consisting,3 o-f 2 diaminopropionic acid (Dpr), 2,4-diaminobutyricd ac (iDbu), Orn, homo-lysine (hLys) and homo-glutam (ihnGeln); X17is Ser(S), Lys(K) or Ala(A), or a non-proteinogenic amino acid selected from the group consistingb ouf, AAib, 2,3-diaminopropionic acid (Dpr), 2,4-diaminobuty aric id (Dbu), Orn, homo-lysine (hLys) and homo-glutamine (hGln); X23and X29are each, independently Met(M) or Nle; X24is Arg(R) or Thr(T); or citrulline or beta-hydronxoyrvaline (β-OH-Nva); X25is Tyr(Y) or Phe(F), or a non-proteinogenic amino acid selected from the group consisting-i oofd 3o- tyrosine (3I-Tyr) and a Ph deerivative; X31 is Arg(R), Lys(K) or Gly(G), preferably Arg(R) o Grly(G); or a non-proteinogenic amino acid selected from the group consisting of citrulline, 2,3-diamopinropionic acid (Dpr), 2,4-diaminobutyric acid (D)b,u Orn, homo-lysine (hLys) and sarcosine (MeGly); X34 is Lys(K) or Arg(R), or a non-proteinogenic amino acid selected from the group consisting,3 o-f 2 diaminopropionic acid (Dpr), 2,4-diaminobutyricd ac (iDbu), Orn, homo-lysine (hLys) and citrulline;X36 is Phe(F), Tyr(Y) or Ser(S), preferably Phe(F) T oyr (Y), more preferably Phe(F), or n aon-proteinogenicamino acid selected from the group consisting obf, A 3i-iodo-tyrosine (3I-Tyr) and a Phe derivative, preferably a Phe derivative, X37 is Gly(G), Ser(S) or Pro(P), preferably Gly(G) P orro(P), or a non-proteinogenic amino acid selected from the group consisting of sarcosine (MeGly), pipecco alciid sarcosine (MeGly), (Pip), azetidine-2-carybliocx acid (Aze), or a deletion; X38 is Lys(K), Arg(R), or a hydrophobic amino acid, p inarticular Lys(K), Arg(R), or Ile(I), preferablyr Ag(R),or a non-proteinogenic amino acid selected from the group consisting,3 o-fd 2iaminopropionic acid (Dpr), 2,4- diaminobutyric acid (Dbu), Orn, homo-lysine (hLy csi)t,rulline, Nva and Nle, preferably citrulline; oar deletion; wherein a Phe-derivative is selected from the gr coounpsisting of - 4-fluoro-phenylalanine, - 4-amino-phenylalanine, - 4-nitro-phenylalanine, - 4-methyl-phenylalanine; and wherein optionally any one of said amino acidsn is al apha-methyl amino acid, in particular at mos atm 5ino acids is / are alpha-methyl amino acid; wherein optionally any one of said amino acidso astit pions from 1 to 10, preferably 1 to 7 and 2124 to is an N-methyl amino acid, in particular at most 5 am aincoids is / are N-methyl amino acid; wherein optionally at most 5 amino acids selecrteodm f X1, X2, X3, X4, X5 is a D amino acid; or a salt thereof, andwherein said inhibitor compound is capable of steivlec ly inhibiting a Kv1.3 potassium channel prot.ein3. The potassium channel inhibitor compound accnogrd toi claim 1 or 2, wherein said polypeptide component comprises thlloew foing amino acid sequence of formula (1): 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 X X X X X X X C X X S X X C X X X C K E A G X X X G K C X N X K C X C X X X(1)(SEQ ID NO: 68); wherein, independently, X1 is Gly(G) or Gln(Q), or a deletion; X2 is Val(V), Thr(T), Lys(K), Ile(I) or Ala(A), or a deletion; X3 is Pro(P), Ile(I), Glu(E), Gly(G), Tyr(Y) or Ar(gR), or a deletion; X4 is Ile(I), Thr(T) or Ala(A), or a deletion; X5 is Asn(N), Pro(P) or Ser(S), or a deletion; X6 is Val(V), Glu(E) or Lys(K), or a deletion; X7 is Pro(P), Lys(K), Glu(E) or Ser(S), or a deolent;i X9 is Thr(T), Ser(S), Lys(K), preferably Thr(T) S orer(S); X10 is Gly(G), His(H) or Ala(A), preferably Gly(G o)r His(H); X12 is Pro(P), Lys(K), Arg(R) or Gly(G); X13 is Gln(Q) or Asp(D), preferably Gln(Q); X15 is Leu(L), Lys(K) or Val(V); preferably Leu(L);X16 is Gln(Q), Glu(E) or Lys(K); preferably Gln(Q o)r Lys(K);X17 is Ser(S), Lys(K) or Ala(A), preferably Ser( oSr) Lys(K); X23 is Met(M) or Nle; X24 is Arg(R) or Thr(T); X25 is Tyr(Y) or Phe(F); X29 is Met(M) or Nle; X31 is Gly(G), Arg(R) or Lys(K), preferably Arg(R o)r Lys(K); X34 is Lys(K) or Arg(R); X36 is Phe(F) or Tyr(Y) or Ser(S), preferably Ph)e o(Fr Tyr(Y);X37 is Gly(G), Pro(P) or a deletion; preferably G(Gly); X38 is Arg(R) or Ile(I), preferably Arg(R), or al deetion; wherein preferably said polypeptide component coismepsr COOH or CONH2on the C terminus; or a salt thereof, andwherein said inhibitor compound is capable of steivlec ly inhibiting a Kv1.3 potassium channel prot.ein4. The potassium channel inhibitor compound accnogrd toi any one of claims 1 to 3 wherein said polypeptide component comprises thlloew foing amino acid sequence of formula (2) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 X X X X X X X C X X S X X C L X X C K E A G X X X G K C X N X K C X C X X X(2)(SEQ ID NO: 70); wherein, independently, X1 is Gly(G), Gln(Q), or a deletion; X2 is Val(V), Thr(T), Lys(K) or Ile(I), or a deleotin; X3 is Pro(P), Ile(I), Glu(E), Gly(G), Tyr(Y) or Ar(gR), or a deletion; X4 is Ile(I), Thr(T) or a deletion; X5 is Asn(N), Pro(P) or Ser(S), or a deletion; X6 is Val(V), Glu(E) or Lys(K); X7 is Pro(P), Lys(K), Glu(E) or Ser(S), preferab Plryo(P), Lys(K) or Glu(E);X9 is Thr(T), Ser(S) or Lys(K), preferably Thr(T o)r, Ser(S);X10 is Gly(G) or His(H), preferably Gly(G); X12 is Pro(P), Lys(K), Arg(R) or Gly(G), preferab Plyro(P), Lys(K) or Arg(R); X13 is Gln(Q) or Asp(D), preferably Gln(Q);X16 is Gln(Q), Glu(E) or Lys(K), preferably Gln(Q o)r Lys(K);X17 is Ser(S) or Lys(K), preferably Ser(S); X23 is Met(M) or Nle; X24 is Arg(R) or Thr(T); X25 is Tyr(Y) or Phe(F), preferably Tyr(Y); X29 is Met(M) or Nle; X31 is Arg(R) or Gly(G); X34 is Lys(K) or Arg(R); X36 is Phe(F) or Tyr(Y), preferably Phe(F); X37 is Gly(G) or Pro(P), or a deletion; preferably Gly(G) or a dieolne;t X38 is Arg(R) or a deletion; or a salt thereof, wherein preferably said polypeptide component coismepsr COOH or CONH2 on the C terminus,wherein said inhibitor compound is capable of steivlec ly inhibiting a Kv1.3 potassium channel prot,e ain dwherein preferably said inhibitor compound hasn ahnib iition selectivity value of at least 100 overth bo Kv1.2 and Kv1.1 proteins.

5. The potassium channel inhibitor compound accnogrd toi any one of claims 1 to 4, wherein said polypeptide component comprises thlloew foing amino acid sequence of formula (3)1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 X X X X X X X C X G S X X C L X X C K E A G X X X G K C X N X K C X C X X X(3)(SEQ ID NO: 72); wherein, independently, X1 is Gly(G) or Gln(Q), or a deletion; X2 is Val(V), Ile(I), Thr(T), or a deletion;X3 is Pro(P), Ile(I), Glu(E), Gly(G) or Tyr(Y), o ar deletion;X4 is Ile(I), Thr(T) or a deletion; X5 is Asn(N) or Ser(S), or a deletion; X6 is Val(V), Glu(E) or Lys(K); X7 is Pro(P), Lys(K) or Glu(E); X9 is Thr(T) or Ser(S); X12 is Pro(P), Lys(K) or Arg(R); X13 is Gln(Q) or Asp(D), preferably Gln(Q);X16 is Gln(Q), Glu(E) or Lys(K), preferably Gln(Q o)r Lys(K);X17 is Ser(S) or Lys(K), preferably Ser(S); X23 is Met(M) or Nle; X24 is Arg(R) or Thr(T); X25 is Tyr(Y) or Phe(F), preferably Tyr(Y); X29 is Met(M) or Nle; X31 is Arg(R) or Gly(G); X34 is Lys(K) or Arg(R); X36 is Phe(F) or Tyr(Y), preferably Phe(F); X37 is Gly(G) or Pro(P), or a deletion, prefera Gbllyy(G) or a deletion; X38 is Arg(R) or a deletion; or a salt thereof; wherein preferably said polypeptide component coismepsr COOH or CONH2 on the C terminus,wherein said inhibitor compound is capable of steivlec ly inhibiting a Kv1.3 potassium channel prot,e ain dwherein preferably said inhibitor compound hasn ahnib iition selectivity value of at least 1000 oveorth b Kv1.2 and Kv1.1 proteins.

6. The potassium channel inhibitor compound accnogrd ainy one of claims 1 to 5, wherein said polypeptide component comprises thlloew foing amino acid sequence of formula (4) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 X X X X X X X C X G S X X C L X X C K E A G X X X G K C X N X K C X C F X X(4)(SEQ ID NO: 74); wherein X1 is Gly(G) or Gln(Q), or a deletion; X2 is Val(V), Ile(I) or Thr(T), or a deletion;X3 is Pro(P), Ile(I), Glu(E), Gly(G) or Tyr(Y), o ar deletion;X4 is is Ile(I) or Thr(T), preferably Ile; X5 is Asn(N) or Ser(S); X6 is Val(V), Glu(E) or Lys(K); X7 is Pro(P), Lys(K) or Glu(E);X9 is Thr(T) or Ser(S); X12 is Pro(P), Lys(K) or Arg(R); X13 is Gln(Q) or Asp(D), preferably Gln(Q);X16 is Gln(Q), Glu(E) or Lys(K), preferably Gln(Q o)r Lys(K); in particular Gln(Q);X17 is Ser(S) or Lys(K), preferably Ser(S); X23 is Met(M) or Nle; X24 is Arg(R) or Thr(T); X25 is Tyr(Y) or Phe(F); X29 is Met(M) or Nle; X31 is Arg(R) or Lys(K); X34 is Lys(K) or Arg(R); X37 is Gly(G) or a deletion; X38 is Arg(R) or a deletion; or a salt thereof; wherein preferably said polypeptide component coismepsr COOH or CONH2on the C terminus,wherein said inhibitor compound is capable of steivlec ly inhibiting a Kv1.3 potassium channel prot.ein7. The potassium channel inhibitor compound accnogrd toi any one of claims 1 to 6, wherein said polypeptide component comprises thlloew foing amino acid sequence of formula (5) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 X X X IX X X C X G S X Q C L X X C K E A G X X X G K C X N X K C X C F X X(5)(SEQ ID NO: 77); wherein X1 is Gly(G) or Gln(Q), or a deletion; X2 is Val(V) or Thr(T), or a deletion;X3 is Pro(P), Ile(I), Glu(E), Gly(G) or Tyr(Y), o ar deletion;X5 is Asn(N) or Ser(S); X6 is Val(V), Glu(E) or Lys(K); X7 is Pro(P), Lys(K) or Glu(E); X9 is Thr(T) or Ser(S); X12 is Pro(P), Lys(K) or Arg(R); X16 is Gln(Q) or Lys(K), in particular Gln(Q); X17 is Ser(S) or Lys(K), preferably Ser(S); X23 is Met(M) or Nle; X24 is Arg(R) or Thr(T); X25 is Tyr(Y) or Phe(F); X29 is Met(M) or Nle; X31 is Arg(R) or Lys(K); X34 is Lys(K) or Arg(R); X37 is Gly(G) or a deletion; X38 is Arg(R) or a deletion; wherein preferably said polypeptide component coismepsr COOH or NH2 on the C terminus;or a salt thereof; andwherein said inhibitor compound is capable of steivlec ly inhibiting a Kv1.3 potassium channel prot.ein8. The potassium channel inhibitor compound accnogrd toi any one of claims 1 to 7, wherein said polypeptide component comprises thlloew foing amino acid sequence of formula (6) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 X X X IN V P C X G S P Q C L X X C K E A G X X X G K C X N X K C X C F X X(6)(SEQ ID NO: 79); wherein X1 is Gly(G) or Gln(Q), or a deletion; X2 is Val(V) or Thr(T), or a deletion;X3 is Pro(P), Ile(I), Glu(E), Gly(G) or Tyr(Y), o ar deletion;X9 is Thr(T) or Ser(S); X16 is Gln(Q) or Lys(K), in particular Gln(Q); X17 is Ser(S) or Lys(K), preferably Ser(S); X23 is Met(M) or Nle; X24 is Arg(R) or Thr(T); X25 is Tyr(Y) or Phe(F), preferably Tyr(Y); X29 is Met(M) or Nle; X31 is Arg(R) or Lys(K); X34 is Lys(K) or Arg(R); X37 is Gly(G) or a deletion; X38 is Arg(R) or a deletion; wherein preferably said polypeptide component coismepsr COOH or CONH2 on the C terminus; or a salt thereof; andwherein said inhibitor compound is capable of steivlec ly inhibiting a Kv1.3 potassium channel prot.ein9. The potassium channel inhibitor compound accnogrd toi any one of claims 1 to 5, wherein said poplytipdecomponent comprises the following amino acid seqceue onf formula (7): 1 2 3 4 5 6 7 8 9 1011121314151617181920212223242526272829303132333435363738 X1 X2 X3 X4 X5 X6 X7 C X9 G S X12 Q C L X16 X17 C K E A G X23 X24 X25 G K C X29 N R K C K C F G X38 (7) (SEQ ID NO: 83); wherein, X1 is Gly(G), Gln(Q), or a deletion; X2 is Val(V), or Ile(I), or a deletion; X3 is Pro(P), Glu(E), Tyr(Y), or a deletion; X4 is Ile(I), Thr(T), or a deletion; X5 is Asn(N), Ser(S), or a deletion; X6 is Val(V), or Lys(K); X7 is Pro(P), Lys(K), or Glu(E); X9 is Thr(T), or Ser(S); X12 is Pro(P), or Lys(K); X16 is Gln(Q), Glu(E) or Lys(K);X17 is Ser(S), or Lys(K); X23 is Met(M) or Nle;X24 is Arg(R) or Thr(T);X25 is Tyr(Y) or Phe(F); X29 is Met(M) or Nle; X38 is Arg(R) or a deletion; or a salt thereof, wherein preferably said polypeptide component coismepsr COOH or CONH2 on the C terminus,wherein said inhibitor compound is capable of steivlec ly inhibiting a Kv1.3 potassium channel prot.ein10. The potassium channel inhibitor compound acincogr tdo claim 9, wherein said polypeptide component comprises the following amino acid sequence of fuolarm (8): 1 2 3 4 5 6 7 8 9 1011121314151617181920212223242526272829303132333435363738 G V X3I N V X7C X9G S P Q C L X16X17C K E A G X23X24Y G K C X29N R K C K C F G X38(8) (SEQ ID NO:84); wherein, X3 is Pro(P), or Glu(E); X7 is Pro(P), or Lys(K); X9 is Thr(T), or Ser(S);X16 is Gln(Q), or Lys(K);or a salt thereof. wherein preferably said polypeptide component coismepsr COOH or CONH2on the C terminus,wherein said inhibitor compound is capable of steivlec ly inhibiting a Kv1.3 potassium channel prot.ein11. The potassium channel inhibitor compound acincogr tdo claim 10, wherein said polypeptide component comprises the following amino acid sequence of fuolarm (9): 1 2 3 4 5 6 7 8 9 1011121314151617181920212223242526272829303132333435363738 G V P I N V P C T G S P Q C L X16S C K E A G M X24Y G K C M N R K C K C F G X38(9) (SEQ ID NO: 85); or a salt thereof. wherein preferably said polypeptide component coismepsr COOH or CONH2on the C terminus,wherein said inhibitor compound is capable of steivlec ly inhibiting a Kv1.3 potassium channel protein12. The potassium channel inhibitor compound acincogr tdo claim 1, having a sequence selected from gr thouep consisting of: VGINVKCTGSKQCLQSCKEAGMTYGKCMNRKCKCYPR (SEQ ID NO 9,) TIINEKCSGSRDCLQSCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO 1),1 TIINEKCTGSKQCLQSCKEAGMTYGKCMNGKCRCF (SEQ ID NO 12), QIYTSKECTGSKQCLQSCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO71), GVEINVKCSGSPQCLQSCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO02), GVPINVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO2) 2,TIINEKCTGSKQCLQSCKEAGMRYGKCMNGKCRCF (SEQ ID NO 26), GVPINVPCTGSPQCLQSCKEAGMTYGKCMNGKCKCFGR (SEQ ID NO9) 2, GVPINVPCTGSPQCLQSCKEAGMRFGKCMNRKCKCFGR (SEQ ID NO0) 3, GVPINVPCTGSPQCLQSCKEAGMRYGKCMNRKCKCFGR (SEQ ID NO2) 3, GVPINVPCTGSPQCLESCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO4) 3, GVPINVPCTGSPQCLKSCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO53), GVPINVPCTGSPQCLQKCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO63), INVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO 37), VPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO 38), GVPINVPCTGSPQCLQSCKEAG(Nle)RYGKC(Nle)NRKCKCFGam-ide^(SEQ ID NO 48), GVPINVPCTGSPQCLQSCKEAGMRYGKCMNRKCKCFGRam- ide^(SEQ ID NO 49), GVPINVPCTGSPQCLQSCKEAGMRYGKCMNRKCKCFGa-mide (SEQ ID NO 50), GVPINVPCTGSPQCLQSCKEAGMRYGKCMNRKCKCFG (SEQ ID NO) 5,1 GVPINVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGRa-mide (SEQ ID NO 52), GVPINVPCTGSPQCLQSCKEAG(Nle)RYGKC(Nle)NRKCKCF^G (SEQ ID NO 53), GVPINVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFG (SEQ ID NO) 5,4 GVPINVPCTGSPQCLQSCKEAG(Nle)TYGKC(Nle)NRKCKCFGR (SE IQD NO 55), and GVPINVPCTGSPQCLKSCKEAGMRYGKCMNRKCKCFGa-mide (SEQ ID NO 57); or a salt thereof.

13. The potassium channel inhibitor compound acincogr tdo claim 1, having the sequence GVPINVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGR (SEQ ID NO2) 2; or a salt thereof.

14. The potassium channel inhibitor compound acincogr tdo claim 1, having the sequence GVPINVPCTGSPQCLQSCKEAGMRYGKCMNRKCKCFGRam- ide^(SEQ ID NO 49); or a salt thereof.

15. The potassium channel inhibitor compound acincogr tdo claim 1, having the sequence GVPINVPCTGSPQCLQSCKEAGMRYGKCMNRKCKCFGa-mide (SEQ ID NO 50); or a salt thereof.

16. The potassium channel inhibitor compound acincogr tdo claim 1, having the sequence GVPINVPCTGSPQCLQSCKEAGMRYGKCMNRKCKCFG (SEQ ID NO) 5;1 or a salt thereof.

17. The potassium channel inhibitor compound acincogr tdo claim 1, having the sequence GVPINVPCTGSPQCLQSCKEAGMTYGKCMNRKCKCFGRa-mide (SEQ ID NO 52); or a salt thereof.

18. The potassium channel inhibitor compound acincogr tdo claim 1, having the sequence GVPINVPCTGSPQCLKSCKEAGMRYGKCMNRKCKCFGa-mide (SEQ ID NO 57); or a salt thereof.

19. The potassium channel inhibitor compound acincogr tdo any one of claims 1 to 18, consisting esiasellynt of the Kv1.3 inhibitor polypeptide component or a s thaeltreof.

20. The potassium channel inhibitor compound acincogr tdo any one of claims 1 to 18, which is selected from the group consisting of a - fusion protein, and a - protein conjugate.

21. A pharmaceutical composition comprising thea pssoitum channel inhibitor compound according to o anney of claims 1 to 20, and a pharmaceutically accepeta ebxcl ipient or carrier, preferably wherein said pharmaceutical composi itsio fnormulated with a polymer for controlled or sauisnted release of the potassium channel inhibitor compo. und 22. The pharmaceutical composition according toim cl 2a1 as formulated for parenteral administratiorn f injection, preferably wherein said pharmaceuticoaml cposition is formulated for subcutaneous, intracmuulasr or intravenous injection.

23. The pharmaceutical composition according toim cl 2a2, as formulated for subcutaneous injection.

24. The pharmaceutical composition according toim cl 2a1, as formulated for inhalation, preferably wrehine said pharmaceutical composition is formulated for inatrsaanl or pulmonary administration.

25. The potassium channel inhibitor compound acincogr tdo any one of claims 1 to 20 for use in theat tmreent or prevention of a disease in a subject, whereinw foinllog administration of the inhibitor compound toid s saubject, the inhibitor compound is capable of selectivelhyib initing a Kv1.3 potassium channel protein.

26. The potassium channel inhibitor compound foer a ucscording to claim 25, wherein the inhibitor coomunpdselectively inhibits Kv1.3 over Kv1.1 and / or Kv1 b.2y a factor of at least 2000.

27. The potassium channel inhibitor compound foer a ucscording to claim 25, wherein the inhibitor coomunpdselectively inhibits Kv1.3 over Kv1.1 and / or Kv1 b.2y a factor of at least 10000.

28. The potassium channel inhibitor compound foer a ucscording to claim 25, wherein the inhibitor coomunpdselectively inhibits Kv1.3 over Kv1.1 and / or Kv1 b.2y a factor of at least 50000.

29. The potassium channel inhibitor compound acincogr tdo any one of claims 1 to 20 or the pharmaceaul ti composition according to any one of claims 21 t,o fo 2r4 use in the treatment or prevention of a dsisee oar for use in the in vivo diagnosis of a disease in a subject; preferableyre wihn the level of Kv1.3 is elevated in said subject in cells associated with the disease.

30. The potassium channel inhibitor compound acincogr tdo any one of claims 1 to 20 or the pharmaceaul ti composition according to any one of claims 21 t,o fo 2r4 use in the treatment or prevention in o vrivo diagnosis of an immunological disorder, preferably inflammoant,i preferably in chronic inflammatory diseasesc,lu indingautoimmune disease; wherein preferably, the inflamtomry disorder or disease is a T cell mediatedr d eisro,preferably an effector memory T cell (Tem cell) miaetedd disorder.

31. The potassium channel inhibitor compound acincogr tdo any one of claims 1 to 20 or the pharmaceaul ti composition according to any one of claims 21 t,o fo 2r4 use in the treatment or prevention of can pcreerf,erablywherein the level of Kv1.3 channel protein is eltev da.

32. The potassium channel inhibitor compound acincogr tdo any one of claims 1 to 20 or the pharmaceaul ti composition according to any of claims 22 to 24r, u fsoe in the treatment or prevention of a neuraominfml atory or a neurological disorder, preferably wherein l tehveel of Kv1.3 channel protein is elevated.

33. An in vitro diagnostic use of the potassium channel inhib ciotomrpound according to any one of claims 1 to20 wherein the binding of said potassium channheilb in tor compound to a Kv1.3 potassium channel itsec dte din a sample obtained from a subject, wherein preferably said potassium channel inhib citoomrpound comprises a detectable label.

34. An in vitro diagnostic method for the diagnosis of a diseass dee afined in any one of claims 29 to 32, wherein - a biological sample is provided from said sub,je scatid sample comprising expressing Kv1.3 potass cihuamnnel proteins, - the potassium channel inhibitor compound accogrd toin any one of claims 1 to 20 is added to the sleam top contact the inhibitor compound with the Kv1.3 postiuams channel proteins,- binding of the potassium channel inhibitor comnpdou to the Kv1.3 potassium channel proteins is dte dte.c35. The in vitro diagnostic method according to claim 34, said modet ahlso comprising the following steps:- quantifying the binding of the potassium chan in heilbitor compound to the Kv1.3 potassium channreolte pins,wherein the level of binding correlates with thvee lle of the expressed Kv1.3 potassium channel pnrsot ieni the sample, - comparing the level of the expressed Kv1.3 poiutamss channel proteins in the sample with a normvaell l,e wherein if the level of the expressed Kv1.3 potuamss cihannel proteins in the sample is higher th naonr amal level, considering the subject as having the deise thaes diagnosis of which was expected or assumed.

36. A nucleic acid molecule encoding potassiumn cheal n inhibitor compound according to any one ofm clsai 1 to 20, wherein each of the amino acid residues of thes psoiutam channel inhibitor compound is a proteinoge anmicino acid residue, and wherein any conjugating moiety, if present, alsnos cisot of proteinogenic amino acid residue(s).

37. A vector comprising the nucleic acid molecucleco arding to claim 36.

38. A cell comprising the nucleic acid moleculeo arcdcing to claim 36 or the vector according to cla 3i7m.

Images