28 results about "Pomalidomide" patented technology

Embodiments described herein relate to methods of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof, and pomalidomide, to the subject to treat the multiple myeloma.

The invention discloses a pharmaceutical composition for treating tumors and application thereof. According to the invention, the BrTAC with anti-tumor activity is constructed by adopting a specific branched skeleton and ligand molecules such as pomalidomide and BI 2536, and the degradation efficiency of target protein PLK1 can be greatly improved. Fluorescence imaging results prove that BrTAC can induce liquid-liquid phase separation in cells, and in-vivo experiment results show that compared with traditional bivalent PROTAC, BrTAC has a better effect in the aspect of PLK1 degradation.

This invention relates to pharmaceutical compositions, including compositions adapted for intranasal administration, comprising an active ingredient, including dexmedetomidine, pomalidomide, a selective phosphodiesterase type 4 inhibitor such as roflumilast, or combinations thereof, useful in the treatment of traumatic brain injury (TBI), including to prevent or reduce the neurological sequalae of TBI.

Embodiments of the invention relate to methods of treating multiple myeloma in a subject in need thereof by administering a therapeutically effective combination regimen comprising a GPRC5DxCD3 bispecific antibody and one or more of pomalidomide, daratumumab, or lenalidomide.

The invention discloses a pomalidomide-heterocyclic derivative for tumor treatment and application of the pomalidomide-heterocyclic derivative. The pomalidomide-heterocyclic ring derivative has the following structure as shown in the specification.

The invention discloses a proteolysis targeting chimeric molecule capable of degrading PTBP1 in a targeting manner as well as a preparation method and application of the proteolysis targeting chimeric molecule. The invention relates to a protease targeted chimeric RNA-PTAC of a nucleic acid ligand. The protease targeted chimeric RNA-PTAC is formed by connecting an E3 ubiquitin ligase ligand pomalidomide and an RNA fragment capable of being specifically combined with PTBP1 protein through polyethylene glycol Linker. The invention relates to an RNA-PROTAC (Ribonucleic Acid-PROTAC) brain targeting delivery preparation, which is a complex obtained by coupling cell penetrating peptides TAT and RVG (Recombinant Virus Growth) with the RNA-PROTAC. According to the TR + RNA-PROTAC complex disclosed by the invention, the targets of efficiently degrading PTBP1 protein in vitro and degrading PTBP1 protein in a brain in a targeted manner in vivo are achieved through the complex, and in-vivo experiments also prove that the TR + RNA-PROTAC complex can be used for treating learning and memory disorders of mice caused by A beta and shows a good curative effect of resisting Alzheimer's disease.

The application discloses a kind of PROTAC molecules with crizotinib as target head, preparation method and application, belong to the field of biological medicine;Preparation method includes: chloro carboxylic acid, thionyl chloride and anhydrous DMF are mixed, after heating reflux reaction, remove thionyl chloride, obtain acyl chloride;Pomalidomide, acyl chloride, organic solvent are mixed and reacted, then filtered to obtain intermediate M;Intermediate M, crizotinib, Na2CO3 are mixed and reacted, then filtered to obtain the PROTAC molecule with crizotinib as target head.The in vitro biological evaluation shows that the new PROTAC molecule can efficiently and selectively induce ubiquitination and degradation of target protein, and exhibits significant antiproliferative activity in drug-resistant tumor cell models and animal models;The application proves that the PROTAC molecule has great potential in overcoming drug resistance of traditional inhibitors, and provides a promising lead compound for developing new therapies for treating refractory diseases such as cancer.

The present application provides an isolated compound which is a related substance of paritaprevir mesylate. The present application also provides the use of said compound for the preparation of paritaprevir mesylate or a composition comprising paritaprevir mesylate.

This invention discloses a PROTAC compound targeting the STING protein, its preparation method, and its applications. The PROTAC compound includes an H-151 small molecule inhibitor, multiple PEG units as linkers, and pomalidomide as a ligand targeting CRBN ligase. The PROTAC compound of this invention can be used as an anti-inflammatory agent and a drug for the treatment of acute kidney injury. It exhibits excellent STING degradation activity and induces STING degradation through the ubiquitin-proteasome pathway, specifically by inhibiting downstream signaling and inflammatory factor release in the STING pathway at the cellular level, and demonstrates good in vivo safety in normal cell lines. Furthermore, the PROTAC compound exhibits a more significant in vivo anti-AKI effect than the small molecule inhibitor H-151, effectively inhibiting innate immune activation, STING signaling pathway transduction, and inflammatory factor release, thereby improving kidney injury and inflammatory responses.

Provided herein are methods and compositions for treating multiple myeloma, such as relapsed and / or refractory multiple myeloma and newly-diagnosed multiple myeloma, including transplant-ineligible newly-diagnosed multiple myeloma (TI-NDMM). The methods involve administering to human patients diagnosed with multiple myeloma an anti-BCMA antigen binding protein (e.g., an anti-BCMA antibody or anti-BCMA antibody drug conjugate) in combination with lenalidomide, pomalidomide, bortezomib, carfilzomib and / or dexamethasone.

Methods of treating, preventing and / or managing multiple myeloma are disclosed. Specific methods include administering an immunomodulatory compound, e.g., lenalidomide or pomalidomide with an anti-CS1 antibody, e.g., elotuzumab, to patients who have undergone autologous stem cell transplantation.

The present invention relates to: a novel pomalidomide derivative exhibiting effects better than those of pomalidomide; a preparation method therefor; and use thereof. The novel pomalidomide derivative according to the present invention has excellent binding force to cereblon, has low cytotoxicity, has a low potential for causing teratogenic side effects, can regulate the expression of TNF-α and proinflammatory cytokines, and has excellent in vivo pharmacokinetic stability even while inhibiting oxidative stress, and thus is expected to exhibit effects better than those of commercial thalidomide-based drugs.

The invention discloses a preparation method and application of a protein degradation agent targeting cGAS. The invention relates to a protein degradation targeting chimera cGAS-dsDNATAC, which is formed by linking a high-specificity ligand and a CRBN ligand pomalidomide through polyethylene glycol Linker, wherein the high-specificity ligand is in non-covalent binding with cGAS protein. According to the present invention, the dsDNA sequence is adopted as the high affinity recognition ligand of the cGAS, the PROTAC strategy is combined, and the coupled pomalidomide ligand efficiently recruits the E3 ubiquitin ligase to form the cGAS-PROTAC-CRBN ternary complex so as to achieve the efficient degradation of the proteasome pathway mediated cGAS protein, such that the innovative path is provided for AD neuroinflammation improvement and disease intervention. Compared with an existing cGAS small-molecule inhibitor, the cGAS small-molecule inhibitor has the advantages that the selectivity on cGAS protein action of different species is improved, and efficient inhibition on cGAS-STING pathways of different species is achieved.

The present disclosure provides methods for treating multiple myeloma. In certain embodiments, the present methods comprise administering to a subject in need thereof a BCMA inhibitor (e.g., a bispecific antibody or antigen-binding fragment thereof that binds to BCMA and CD3) in combination with an immunomodulator. In certain embodiments, the immunomodulator is a structural or functional analogue of thalidomide (e.g., lenalidomide or pomalidomide). In certain embodiments, the subject has been previously treated with one or more anti-cancer therapies.

The present invention relates to a novel pomalidomide derivative that exhibits improved effects compared to pomalidomide, and its manufacturing method and use. The novel pomalidomide derivative according to the present invention has excellent binding ability to cereblon, almost no cytotoxicity, low possibility of teratogenic side effects, can regulate TNF-α and proinflammatory cytokine expression, and has excellent pharmacokinetic stability in vivo while suppressing oxidative stress, and is expected to have improved effects compared to commercially available thalidomide drugs.

The invention discloses an application of Pomalidomide in preparation of a medicine for long-term immune reconstitution of an HIV (human immunodeficiency virus) patient. According to the application disclosed by the invention, the research finds that pomalidomide can be used for remarkably inhibiting the replication of HIV-1 in MT-4 and Jurkat cell lines, primary CD4 + T cells and humanized mouse models for the first time, and the Pomalidomide can be used for increasing the quantity of CD4 + T and the ratio of CD4 to CD8, increasing the activation of T cells, reducing the depletion of the T cells and promoting immune reconstruction no matter in a cell model or a mouse model. The invention provides a theoretical basis for research and development of medicines for long-term immune reconstitution of HIV patients, opens up a new application of Pomalidomide, provides a brand new method for treating HIV infection and promoting long-term immune reconstitution of HIV patients, and has a wide application prospect in the technical field of treatment of HIV infection.

The present invention relates to clinically proven subcutaneous pharmaceutical compositions comprising anti-CD38 antibodies and methods of their uses in combination with pomalidomide and dexamethasone.

The invention provides application of pomalidomide and derivatives thereof as electrochemical luminescence probes. Pomalidomide and a derivative probe thereof are respectively added into a potassium persulfate co-reactant solution, and an electrochemical luminescence reaction is carried out to generate an electrochemical luminescence signal. By modifying the molecular structure of the pomalidomide, the butyne derivative in the pomalidomide derivative has higher ECL efficiency (125%) and longer emission wavelength (696 nm) than classical ruthenium dipyridyl, can be prevented from being interfered by high-potential side reaction, and can effectively avoid ultraviolet region interference of a complex matrix through a near-infrared electrochemical luminescence signal; therefore, the method has a wider application prospect in the field of medical examination.

The application relates to the technical field of medicine synthesis, in particular to synthesis and application of a PROTAC small molecule. The application designs a PROTAC small molecule capable of specifically degrading CBX3. Test results show that the PROTAC small molecule with the structure of QTARK(Me3)T-(NH-PEG4-CH2COOH-) -Pomalidomide can reduce the CBX3 protein expression level in prostate cancer, and has the effect of preventing cancer.

The invention discloses a PROTAC medicine for targeted degradation of ACLY protein and a preparation method and application of the PROTAC medicine, and belongs to the technical field of medicine. The structure of the PROTAC drug for targeted degradation of the ACLY protein is shown as a general formula A-L-B, A is an ACLY protein ligand NDI-091143 or a derivative thereof, L is a connecting chain, and B is a small molecule ligand of E3 ubiquitin ligase protein; the connecting chain is connected with A and B through covalent bonds; the micromolecular ligand of the E3 ubiquitin ligase protein is at least one of pomalidomide, thalidomide, lenalidomide or a derivative thereof; the PROTAC drug for targeted degradation of the ACLY protein is applied to preparation of an ACLY protein degradation agent and preparation of drugs for prevention and / or treatment of MAFLD, obesity or diabetes mellitus.

The present invention relates to a use of a novel pomalidomide derivative which is for treating brain diseases, and exhibits improved pharmacological effects as compared to pomalidomide. The novel pomalidomide derivative according to the present invention exhibits excellent binding to cereblon, has almost no cytotoxicity, is unlikely to cause teratogenic adverse effects, can control TNF-α expression, exhibits excellent in vivo pharmacokinetic stability while suppressing oxidative stress, ameliorates a decrease in motor function which is a symptom of Parkinson's disease, and increases tyrosine hydroxylase expression which is reduced by Parkinson's disease, and thus can be used for preventing or treating brain diseases such as Parkinson's disease.

The application discloses application of pomalidomide in preparation of a medicine for preventing or treating seizures of Dravet syndrome or an antiepileptic medicine, and relates to the technical field of Dravet syndrome and medicines for preventing and treating epilepsy. The application discloses application of pomalidomide in preparation of a medicine for preventing or treating seizures of Dravet syndrome or an antiepileptic medicine. The epilepsy intervention potential of pomalidomide is verified in a mouse model of Dravet syndrome related to SCN1A mutation for the first time. The pomalidomide can significantly increase a body temperature threshold required for seizures, reduce a seizure duration, reduce a Racine score grade, and improve long-term survival rate, and thus indicates that the pomalidomide has significant neuroprotective and anti-seizure abilities. Intervention of the pomalidomide on an early stage of immune activation can also effectively reduce a subsequent seizure risk, which has a reference value for "pre-heat drug administration" or "intervention on children with high infection risk" in the clinic.

The invention discloses a benzodioxolame and pomalidomide combined compound as well as a preparation method and application thereof. The structural formula of the compound is as shown in formula I in the specification. The compound disclosed by the invention has good tumor inhibition activity and relatively high application value.

(3R, 4S)-3-(4-hydroxy-3,5-dimethoxyphenyl)-4-(4-hydroxyphenyl)-8-methyl-3,4-dihydro-2H- chromen-7-ol (TRX-E-002-1) for use in a method of treatment for a hematological cancer being acute myeloid leukemia or multiple myeloma in a subject in need thereof, the method comprising administering to the subject an effective amount of TRX-E-002-1. The method may further comprise administering to the subject an effective amount of a second compound selected from the group consisting of (i) a BCL-2 inhibitor such as venetoclax, navitoclax or obatoclax, (ii) a deoxycytidine analogue chemotherapeutic such as cytarabine or gemcitabine, (iii) a hypomethylating agent such as azacitidine or decitabine, (iv) an anthracycline chemotherapeutic such as daunorubicin, doxorubicin, epirubicin, idarubicin, valrubicin or mitoxantrone, (v) a proteasome inhibitor such as carfilzomib, bortezomib, and ixazomib, (vi) an immunomodulatory drug such as pomalidomide, lenalidomide, and thalidomide and(vii) a corticosteroid drug such as dexamethasone or prednisone, and (viii) an alkylator such as bendamustine, cyclophosphamide, melphalan, and melflufen. Corresponding combination pharmaceutical compositions.

The invention provides a glycosylated phthalimide compound as shown in a formula (I), and an isomer, a solvate or a hydrate or a pharmaceutically acceptable salt of the glycosylated phthalimide compound. The invention further provides a preparation method and application of the glycosylated phthalimide compound, the isomer or the pharmaceutically acceptable salt of the glycosylated phthalimide compound in the technical scheme. The compound provided by the invention can effectively inhibit proliferation of multiple myeloma forming drug resistance to existing clinical drugs lenalidomide and pomalidomide, has higher inhibitory activity to brain glioma, and can be used as a lenalidomide and pomalidomide drug-resistant myeloma treatment drug and a potential drug for brain tumor treatment.

The invention discloses a PROTAC compound derived based on chlorogenic acid as well as a preparation method and application of the PROTAC compound, and relates to the technical field of medicinal chemistry and PROTAC. The structure of the PROTAC compound derived based on chlorogenic acid is shown as a formula I. The preparation method of the PROTAC compound derived based on chlorogenic acid comprises the following steps: taking chlorogenic acid and pomalidomide with linkers with different lengths as raw materials, and synthesizing PROTAC with anticancer activity through an amide condensation reaction. The anticancer activity of the chlorogenic acid-derived PROTAC compound is remarkably improved compared with that of chlorogenic acid, proliferation of cancer cells A375 is effectively inhibited, and the chlorogenic acid-derived PROTAC compound can become a novel anticancer drug and has a good development prospect.

The invention discloses an NAPG proteolysis targeting chimera capable of resisting multiple myeloma as well as a preparation method and application of the NAPG proteolysis targeting chimera. The NAPG protein hydrolysis targeting chimera is prepared by connecting (5-phenyl-1H-benzo [d] imidazole-2-yl) methylamine or 4-(2-(aminomethyl)-1H-benzo [d] imidazole-5-yl) benzoic acid and a derivative thereof or connecting the (5-phenyl-1H-benzo [d] imidazole-2-yl) methylamine or 4-(2-(aminomethyl)-1H-benzo [d] imidazole-5-yl) benzoic acid and a derivative thereof with lenalidomide, thalidomide, hydroxyl thalidomide and a pomalidomide E3 ligase ligand through a linker. The compound provided by the invention can effectively degrade multiple myeloma (MM) cells and NAPG protein in exosomes secreted by the MM cells. The degradation effect affects related signal channels to further inhibit proliferation and osteoclast differentiation of MM cells, so that the activity of resisting multiple myeloma is exerted. The compound has a good degradation effect on NAPG protein and has the potential of being developed into a novel NAPG degradation agent medicine.

This invention discloses an arbutin PROTAC, its preparation method, and its application. The structural formula is as follows: [Structure formula would be inserted here], where E3 Ligase is nalidomide or pomalidomide, and the Linker is a first fatty chain, a second fatty chain, or a PEG chain, wherein the first fatty chain is -NH-(CH2). n1 -NH-(CH2)3- CO-, where the second fatty chain is -NH-(CH2). n2 -CH2-NH-, the PEG chain is -NH-(CH2-CH2-O). n3 -CH2-CH2-NH-. This invention shows promising application prospects in the preparation of therapeutic compositions for hyperuricemia and anti-inflammatory compositions, providing new drug candidates for the clinical treatment of related diseases.