54 results about "Pomalidomide" patented technology

The invention discloses erianin PROTACs as well as a preparation method and application thereof, the structural formula of the erianin PROTACs is # imgabs0 #, E3 Ligand is pomalidomide, and Linker is an alkane chain or a PEG chain. The erianin PROTACs disclosed by the invention are superior to the prior art in the aspects of target protein degradation efficiency, anti-tumor activity, innovativeness, application prospect and the like, and show remarkable technical progress and practical value.

The present invention relates to a novel pomalidomide derivative that exhibits improved pharmacological effects compared to pomalidomide, and is used to treat brain diseases. The novel pomalidomide derivative developed in the present invention has excellent binding ability to cereblon, is almost non-cytotoxic, has low possibility of teratogenic side effects, and can regulate TNF-α expression, as well as suppress oxidative stress and has excellent in vivo pharmacokinetic stability, and shows excellent effects of improving the decrease in motor ability, which is a symptom of Parkinson's disease, and increasing the expression of tyrosine hydroxylase, which is decreased in Parkinson's disease, and can be used for the prevention or treatment of brain diseases such as Parkinson's disease.

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.

Compounds and pharmaceutical compositions useful to treat cancer (e.g., lymphoma), neurodegenerative diseases, and autoimmune disorders include (1) a first nucleic acid sequence capable of binding to a transcription factor, for example, a signal transducer and activator of transcription (STAT) factor, such as STAT3, (2) a second nucleic acid sequence capable of binding a Toll-like receptor protein, for example, a CpG oligodeoxynucleotide, and (3) a ubiquitin ligase binding compound capable of binding a ubiquitin ligase protein, for example, a compound that is capable of binding a cereblon protein, such as lenalidomide, pomalidomide, or thalidomide.

The present invention provides methods for treating multiple myeloma (e.g., refractory multiple myeloma or recurrent and refractory multiple myeloma) in an individual who has received at least two prior therapies for multiple myeloma. The methods comprise administering to the individual an anti-CD38 antibody, pomalidomide, and dexamethasone. Methods of ameliorating renal damage in an individual having multiple myeloma are also provided.

The present invention discloses a preparation method of pomalidomide derivatives. The following reaction conditions are used: an organic base and an organic amine raw material shown in formula (II) are added to an organic solvent containing a fluorinated thalidomide raw material shown in formula (I) heated to 140-180 °C. After the reaction is completed, the reaction solution is post-treated and then separated and purified to obtain a pomalidomide derivative shown in formula (III). The reaction time of this preparation method only needs 5-10 minutes, and the yield ranges from 85% to 95%. It solves the problems of long reaction time and difficult product purification in the existing preparation methods, and has the advantages of extremely short reaction time, high yield, easy product purification, and stable process conditions.

Provided are methods for treating hematologic malignancy, especially AML-MRC, MDS and / or MM. Specifically, provided are methods for treating AML-MRC and MDS with a compound of formula (I) or a pharmaceutically acceptable salt thereof, optionally in combination with at least one additional anti-cancer agent such as 5-azacitidine or cytarabine, and treating MM with a compound of formula (I) or a pharmaceutically acceptable salt thereof, optionally in combination with at least one additional anti-cancer agent such as pomalidomide, thalidomide, lenalidomide, and / or dexamethasone.

Described herein are CDK9 degraders that include a CDK9 binding moiety, such as AT7519 or VIP152, conjugated to a E3 ubiquitin ligase binding moiety, such as thalidomide, lenalidomide, or pomalidomide. These degraders can induce the ubiquitination of CDK9 and promote its degradation in cells. The linker covalently tethering the CDK9 binding moiety to the E3 ubiquitin ligase binding moiety can be selected to tune the solubility profile and potency of the degrader. Accordingly, the present disclosure provides compounds, compositions, kits, uses, and methods for the treatment of cancer (e.g., blood cancers such as acute myeloid leukemia or acute lymphoblastic leukemia).

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.

A pomalidomide derivative exhibiting effects better than those of pomalidomide, a preparation method therefor, and use thereof. The pomalidomide derivative 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.

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 present invention discloses a pomalidomide-linked urea feed additive and its preparation method and application, belonging to the technical field of functional feed additive synthesis. The technical solution of the present invention is as follows: the pomalidomide-linked urea feed additive molecule has a structure of 2-Boc aminobenzoic acid as the starting material, first reacting to obtain 2-(2,6-dioxopiperidin-3-yl)-4-aminoisoindoline-1,3-dione, and then converting the amine group on the structure into azide, and obtaining the target compound through a click reaction. The compound is loaded with exosomes by a supercritical method, has a certain inhibitory effect on cattle urease, and can be used as a potential feed additive.

The present invention discloses an artemisinin PROTACs, a preparation method and application thereof, wherein the structural formula is: The present invention uses artemisinin modified product artesunate as POI ligand, lenalidomide and pomalidomide as E3 ligands, and linkers selected from amino acid chains, PEG chains and fatty chains. The anticancer activity thereof is superior to that of artesunate, and the present invention has good potential application prospects in anticancer drugs and treatment of critical malaria.

The invention relates to the field of medical treatment, and discloses a method for detecting whether lenalidomide of a patient with multiple myeloma is effective or not. The method comprises the following steps: treating in-vitro bone marrow mononuclear cells of a subject by using lenalidomide, and respectively detecting the proportion of CD138 + cells and the IKZF1 / 3 expression quantity in cells of a lenalidomide treatment group and an untreated group. The method objectively reflects whether relapse and progression MM patients are resistant to the lenalidomide, if the patients are resistant to the lenalidomide, the patients are replaced with substituted chemotherapeutic drugs such as the lenalidomide and pomalidomide, and if the patients are not resistant to the lenalidomide, the patients are replaced with other chemotherapeutic drugs in the scheme. A theoretical basis is provided for replacing chemotherapeutic drugs for the MM patient, clinical medication is guided, invalid treatment is avoided through precise treatment, and the economic burden of the patient is relieved.

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 invention relates to a novel thalidomide-based compound derivative having significantly improved water solubility due to the introduction of a sugar or sugar derivative into lenalidomide or pomalidomide, which are thalidomide-based compounds, wherein the lenalidomide or pomalidomide derivative according to the present invention has significantly increased water solubility compared to conventional lenalidomide or pomalidomide and can thus be formulated into an injection or eye drop formulation. Therefore, the lenalidomide or pomalidomide derivative can be administered in the form of a high concentration therapeutic agent to a local area, and can be easily administered in combination with a different therapeutic agent developed as an injection or eye drop formulation.

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.

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

The invention relates to a quinazoline derivative and pomalidomide combined compound as well as a preparation method, a pharmaceutical composition and an application of the quinazoline derivative and pomalidomide combined compound. Specifically disclosed is a compound represented by formula I or a pharmaceutically acceptable salt thereof. The compound provided by the invention has good tumor inhibition activity.

The present invention relates to a method for selectively synthesizing 3,6'-dithiopomalidomide from pomalidomide. According to the present invention, the generation of byproduct 1,6-dithiopomalidomide is reduced during the synthesis of 3,6'-dithiopomalidomide, and the synthesis ratio of 3,6-dithiopomalidomide is selectively increased to more than 90%, thereby reducing the time and cost required for separating 1,6-dithiopomalidomide by HPLC or the like in the subsequent purification process, thereby having the advantages of improving the productivity and economy of 3,6'-dithiopomalidomide compounds.

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.