53 results about "Enzalutamide" patented technology

The present disclosure provides a pharmaceutical composition that includes enclomiphene and pregnenolone, and pharmaceutical combinations and uses thereof. The present disclosure also provides a pharmaceutical combination that includes a selective estrogen receptor modulator and testosterone in a form suitable for oral administration, and uses thereof.

The present disclosure provides a pharmaceutical composition that includes enclomiphene and pregnenolone, and pharmaceutical combinations and uses thereof. The present disclosure also provides a pharmaceutical combination that includes a selective estrogen receptor modulator and testosterone in a form suitable for oral administration, and uses thereof.

The present disclosure includes methods, pharmaceutical compositions, and kits for the treatment of prostate cancer, wherein AZD5305 and enzalutamide are dosed in combination to a subject in need.

This invention relates to talazoparib, or a pharmaceutically acceptable salt thereof, in combination with enzalutamide, or a pharmaceutically acceptable salt thereof, for the treatment of homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer and methods of increasing overall survival thereof.

Methods and uses of increasing or accelerating liver regeneration in a subject in need thereof are provided. In some aspects, such methods and uses comprise administering an effective amount of an androgen receptor inhibitor to a subject in need thereof, including, but not limited to, a subject suffering from one or more risk factors of post-hepatectomy liver failure. Any androgen receptor is contemplated for use in the methods described herein including, but not limited to, enzalutamide, apalutamide, bicalutamide, darolutamide, flutamide, nilutamide, or proxalutamide.

Provided herein are methods of identifying a subject with prostate cancer (such as a human or veterinary subject) who will respond to enzalutamide therapy. In particular examples, the methods can determine with high accuracy whether a subject is likely to respond to enzalutamide therapy. Also provided are methods for treating a subject who is likely to respond to enzalutamide, for example by administering enzalutamide to the subject.

The invention provides a method for treating AR negative TNBC through combination of quercetin and enzalutamide, the quercetin up-regulates the AR expression level by inhibiting a high-expression solute carrier SLC7A5, so that tumor cells which are not sensitive to enzalutamide originally obtain drug sensitivity again; the combined use of an AR antagonist enzalutamide (1-80 [mu] M) can cooperatively block an AR signal channel and significantly inhibit cell proliferation (the inhibition rate of drug combination is 70%, Plt, 0.01 higher than that of a single drug). In-vitro experiments prove that the scheme has a synergistic effect (the effect is optimal when the mass ratio is 1: 1-5: 1) in MDA-MB-231 cells, and an animal model shows that the tumor volume inhibition rate reaches 70% or above. Safety evaluation shows that the drug combination does not cause abnormity of serum biochemical indexes (ALT / AST / BUN / CREA) or damage of main organs and tissues. The invention further provides a preparation method of an oral preparation (tablets / capsules / nanoparticles) containing quercetin (50-500 mg / day) and enzalutamide (40-160 mg / day), and a new strategy is provided for reversing AR-TNBC drug resistance.

The present invention belongs to the field of biomedicine technology, and relates to the application of the Lnc-FLJ gene in the treatment of castration-resistant prostate cancer. The application of the Lnc-FLJ gene inhibitor in the preparation of prostate cancer drugs. The present invention discovered for the first time that Lnc-FLJ can inhibit the proliferation and autophagy of castration-resistant prostate cancer. Lnc-FLJ is more highly expressed in castration-resistant prostate cancer cells and prostate cancer tissues with higher malignancy. Inhibiting Lnc-FLJ can inhibit the occurrence and development of castration-resistant prostate cancer. The preparation of Lnc-FLJ small molecule inhibitor shRNA is used to treat castration-resistant prostate cancer and cancer insensitive to enzalutamide, thereby inhibiting the AR signaling pathway. The present invention provides new ideas for further studying the pathogenesis of castration-resistant prostate cancer and the function of the Lnc-FLJ gene, and provides a new direction for the development of castration-resistant prostate cancer drugs.

Methods of treating prostate cancer, including castration-resistant prostate cancer and metastatic castration-resistant prostate cancer, comprising administering an effective amount of an androgen receptor (AR) antagonist and an effective amount of a nonsteroidal selective glucocorticoid receptor modulator (SGRM) are disclosed. The AR antagonist may be enzalutamide. The SGRM may be an octahydro fused azadecalin compound, such as exicorilant, ((4aR,8aS)-1-(4-fluorophenyl)-6-((2-methyl-2H-1,2,3-triazol-4-yl)sulfonyl)-4,4a,5,6,7,8,8a,9-octahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(4-(trifluoromethyl)pyridin-2-yl)methanone which has the structure: The AR antagonist and the SGRM may be administered once per day, and may be administered with food. Enzalutamide doses may be 150-200 mg / day, e.g., 160 mg / day. Exicorilant doses may be 100-350 mg / day, e.g., 240 mg / day, or 280 mg / day, or 320 mg / day.

The invention relates to a method for treating a condition and / or sepsis in a subject by administering a therapeutically effective amount of an anti-androgen small molecule. The method involves executing an analytical test to determine if the subject is an appropriate candidate for the treatment. If deemed suitable, the anti-androgen small molecule is administered, resulting in an improvement in the condition and / or sepsis compared to the subject without the treatment. The method also includes assessing the success of the treatment through various analytical tests performed at different time points after administration. The anti-androgen small molecule may include compounds such as sabizabulin, enzalutamide, or others, and is administered in a dose ranging from about 0.05 mg to about 2000 mg per day. The treatment is tailored based on the severity and stage of the condition and adjusted according to the subject's response.

The present invention relates to a solid dispersion comprising enzalutamide or its pharmaceutically acceptable salts, hydroxypropyl methylcellulose phthalate (HPMCP), soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol), surfactant, and optionally at least one pharmaceutically acceptable excipient. The present invention also relates to a pharmaceutical composition comprising the solid dispersion of enzalutamide and its use for treating prostate cancer. The present invention further relates to a process for preparation of the solid dispersion of enzalutamide and the pharmaceutical composition comprising the solid dispersion of enzalutamide.

The invention discloses an anti-prostatic cancer sulfonamide compound and application thereof, and belongs to the technical field of medicines. The structural formula of the sulfonamide compound is shown as a general formula (I), and the structure of the sulfonamide compound is different from that of traditional steroidal and non-steroidal androgen receptor antagonists. The compound has remarkable androgen receptor transcription inhibition activity, can be effectively combined with an androgen receptor ligand binding pocket in a competitive manner, blocks homologous dimerization of an androgen receptor, inhibits nuclear translocation of the androgen receptor, inhibits expression of downstream genes in an androgen receptor signal channel, and can be used for inhibiting the transcription of the androgen receptor. Further, the effects of antagonizing the transcriptional activity of an androgen receptor and inhibiting tumor cell proliferation are achieved; the compound can effectively inhibit the transcriptional activity of a mutant androgen receptor related to the clinical drug resistance of enzalutamide and the proliferation activity of drug-resistant cells, and shows better safety. The invention provides a new choice for prostatic cancer treatment and drug development.

The inventors have prepared a novel anti-Cath-D antibody (F1M1) that can reduce tumor growth in a Cath-D secreting basal-like TNBC cell line with strong immune infiltration, without significant toxicity. The F1M1 antibody prevents recruitment of immunosuppressive M2 polarized tumor-associated macrophages (TAMs) and induces activation of natural killer cells in the tumor, and the F1M1 also enhances activation of antitumor M1 polarized TAM, recruitment and maturation of conventional cDC1 dendritic cells in the tumor to promote antigen presentation and reduce depletion marker expression of CD4 + and CD8 + T cells in the tumor and drainage lymph nodes. It is worthy of noting that the affinity of the antibody F1M1 to Cath-D is better than that of the antibody F1 prepared by the inventor in advance. The inventors also have prepared a novel Fc-optimized F1M1-Fc + human antibody which can promote ADCC induction of cancer cells and CAF, improve anti-tumor efficacy, and trigger recruitment, activation and cytotoxic activity of NK cells in tumors. The F1M1-Fc + F1M1-Fc + can inhibit the growth of MDA-MB-231 and SUM159 TNBC cell xenografts and two TNBC-PDX (one of the TNBC-PDX is resistant to neoadjuvant chemotherapy), and has no obvious toxicity. In addition, the F1M1-Fc < + > improves the treatment effect of the paclitaxel and enzalutamide combined medicine. Thus, the present invention relates to anti-cathepsin-D antibodies and their use in the treatment of cancer, in particular triple negative breast cancer.

The invention provides an analysis method of Enzalocamide. Specifically, the analysis method of the enzaloutamine disclosed by the invention comprises the following step: analyzing a to-be-detected object containing the enzaloutamine by adopting a high performance liquid chromatography. According to the high performance liquid chromatography analysis method, all peaks can be completely separated, the accuracy is high, the stability is high, the sensitivity is good, a technical basis is provided for quality detection of an Enzaloutamide raw material medicine, based on the AQbD concept, specificity, quantitation limit, detection limit, linearity, precision, accuracy, solution stability and method durability verification is carried out on the method, and the method has good application prospects. The result shows that the method is high in specificity, good in reproducibility and high in analysis efficiency.

The application discloses a furan amide compound and application thereof, and belongs to the technical field of medicines.The structural general formula of the furan amide compound is shown as formula (I).The application provides a novel furan amide AR antagonist, the compound and the derivative thereof have obvious antagonistic activity on an androgen receptor, and exhibit good biological activity in in-vivo and in-vitro biological evaluation, the androgen receptor antagonistic activity is better than that of enzalutamide, the compound is effective in an AR F877L / T878A double-point mutant cell model resistant to enzalutamide, the activity is better than that of darolutamide, and the compound has good safety.Therefore, the compound can be applied to the treatment of diseases related to the androgen receptor as an androgen receptor antagonist, including but not limited to the treatment of prostate cancer, breast cancer, ovarian cancer and the like.

The application belongs to the field of pharmaceutical chemical industry and particularly relates to a preparation method of enzalutamide. In the application, N-BOC-2-aminoisobutyramide is used as a starting material to form a ring with phenyl chlorothioformate to obtain 5,5-dimethyl-1-tert-butoxycarbonyl-2-thione imidazole-4-ketone, the obtained product is further subjected to nucleophilic substitution with 2-trifluoromethyl-4-bromobenzonitrile, is deprotected, and is subjected to nucleophilic substitution with 2-fluoro-4-bromobenzamide to obtain enzalutamide. The method uses N-BOC-2-aminoisobutyramide as a starting material, does not produce disubstituted impurities, has higher conversion rate, can obtain a product with high yield, and is more suitable for industrial amplification.

This invention relates to talazoparib, or a pharmaceutically acceptable salt thereof, in combination with enzalutamide, or a pharmaceutically acceptable salt thereof, for the treatment of metastatic castration-resistant prostate cancer and methods of increasing survival thereof.

The invention relates to the technical field of medicine production, and provides an enadostat fumarate crystal, a preparation method thereof and a hydrogel patch. According to the preparation method disclosed by the invention, the enadostat is prepared into the fumarate crystal, so that the solubility of the enadostat can be improved; the hydrogel type patch prepared from the enadostat fumarate crystal can reduce the drug dosage, avoid the first-pass effect, maintain the stable blood concentration and improve the patient compliance, and meanwhile, the hydrogel type patch also has good skin adhesiveness, the characteristic of being suitable for drug release and good physical and chemical stability; wide application prospects are realized.

The application relates to application of PUS1 in improving sensitivity of enzalutamide to prostate cancer treatment. Through bioinformatics analysis and a series of in-vivo and in-vitro experiments, the application first discovers and determines the key role of the expression level of PUS1 in reducing the sensitivity of enzalutamide in treating prostate cancer, and deeply studies the mechanism, and determines that the PUS1 promotes enzalutamide resistance of prostate cancer in dependence on the Psi modification activity. The application enriches the related mechanism of drug resistance generation and regulation in the process of enzalutamide in treating prostate cancer, provides sufficient scientific basis and theoretical basis for exploring new prostate cancer diagnosis, prognosis judgment and treatment molecular target, and developing new targeted drugs, and has important social value and scientific significance.

The present invention relates to a method of using taprazoparib or a pharmaceutically acceptable salt thereof in combination with enzalutamide or a pharmaceutically acceptable salt thereof for treating metastatic castration-resistant prostate cancer with homologous recombination repair (HRR) gene mutations and increasing the survival thereof.

The invention discloses an enadostat impurity and a preparation method thereof, and belongs to the technical field of pharmaceutical chemicals. The preparation method comprises the following steps: firstly, carrying out nucleophilic substitution reaction on a compound 1 and a compound 2 under the action of an acid-binding agent to generate a compound 4; hydrolyzing the compound 4 in an alkaline solution, and carrying out a decarboxylation reaction under an acidic condition to generate a compound 5; then carrying out amide condensation reaction on the compound 5 and the compound 3 under the action of a condensing agent, a solvent and alkali to generate a compound 6; and finally, carrying out hydrolysis reaction on the compound 6 in an alkaline solution and an organic solvent to generate a compound 7. The enrodostat impurity synthesized by the invention can be used for qualitative and quantitative analysis of impurities in production of enrodostat, and is convenient for effective monitoring and timely reduction of impurity content by adopting necessary means, so that the quality standard of the enrodostat intermediate is improved.

Downregulated miR-99b-5p and upregulated mTOR cooperatively promotes the African American (AA) PCa aggressiveness and drug resistance. Nuclear mTOR, AR, and SMARCD1 are highly expressed in AA PCa (MDA PCa 2b) compared to EA PCa (LNCaP) cell line. miR-99b-5p inhibited protein levels of mTOR, AR / AR-V7 and SMARCD1 in cytoplasm and nuclei of EA and AA PCa. miR-99b-5p effectively inhibits cell proliferation / survival and induced cell apoptosis in EA and AA PCa cells. Moreover, combination of miR-99b-5p and enzalutamide (Enz) synergistically enhances the cytotoxicity against aggressive AA PCa and castration resistant prostate cancer (CRPC). miR-99b-5p or miR-99b-5p / Enz significantly reduces the recruitment of mTOR to the genes involved in the metabolic reprogramming in CRPC. miR-99b-5p can function as an epigenomic driver to modulate the mTOR / AR / SMARCD1 signaling axis in AA PCa and resistant CRPC. miR-99b-5p can be utilized as a biomarker for identifying the presence of prostate cancer.

This disclosure provides formulations of enzalutamide and their use for treating hyperproliferative disorders.

The present invention discloses a synthesis method of a key intermediate of enzalutamide, which relates to the technical field of organic synthesis. Using 4-bromo-2-fluorobenzoic acid as the starting material, 4-bromo-2-fluorobenzoic acid reacts with a sulfuric acid ethanol solution to obtain ethyl 4-bromo-2-fluorobenzoate. Ethyl 4-bromo-2-fluorobenzoate undergoes an Ullmann reaction with ammonium chloride under the action of a ligand, a catalyst and an acid-binding agent to obtain ethyl 4-amino-2-fluorobenzoate. The present invention synthesizes the key intermediate ethyl 4-amino-2-fluorobenzoate of enzalutamide through an esterification reaction and an Ullmann reaction. This synthesis method can not only simplify the operation and reduce the cost, but also improve the yields of the intermediate and the product, thus being applicable to industrial production and providing high-quality intermediates for the preparation of enzalutamide.

One embodiment of the present invention provides a pharmaceutical composition in which enzalutamide is amorphized as a result of solid dispersion, and consequently a supersaturated state is maintained. Alternatively, one embodiment of the present invention provides a formulation comprising a pharmaceutical composition in which enzalutamide is amorphized as a result of solid dispersion, and consequently a supersaturated state is maintained. According to one embodiment of the present invention, the pharmaceutical composition includes an enzalutamide solid dispersion comprising enzalutamide in an amorphous form and a base. The pharmaceutical composition includes a pharmaceutically acceptable cationic polymer. The pharmaceutically acceptable cationic polymer may be a pharmaceutically acceptable cationic acrylic polymer or a pharmaceutically acceptable cationic vinyl polymer.

The invention belongs to the technical field of biological medicine, and particularly relates to an NTD inhibitor and application thereof. The invention provides a novel NTD inhibitor, a bisphenol A structure of EPI-001 is replaced by utilizing reasonable drug design means such as skeleton transition, the aromaticity of a core skeleton of a compound is increased, and drug design is developed on the basis of the novel core skeleton. The compound prepared by the invention has proliferation inhibition activity on an enzalutamide drug-resistant cell line, has inhibition activity on transcription of a shear mutant AR-V7, and simultaneously shows a good in-vivo half-life period and certain oral bioavailability.

The invention discloses a synthesis method of a key intermediate 4-bromo-2-fluoro-N-methyl benzamide of an anti-prostatic cancer drug enzalutamide. According to the method, 4-bromine-2-fluorobenzaldehyde (II) is taken as an initial raw material and firstly reacts with phosphorus pentachloride, and then a compound (III) reacts with a methylamine reagent (IV) to prepare the target product 4-bromine-2-fluoro-N-methylbenzamide (I). The method disclosed by the invention has the characteristics of short steps, simple process, simplicity and convenience in operation, high total yield and the like, so that the method has relatively high implementation value and social and economic benefits.

This disclosure provides formulations of enzalutamide and their use for treating hyperproliferative disorders.

An indazole hydrazide compound, as represented in formula (I); wherein, R is selected from substituted alkyl, substituted alkenyl and substituted phenyl; substituent in the substituted alkyl and substituted alkenyl includes phenyl and / or substituted phenyl; R′ is selected from H and alkyl. Compared with the prior art, the above indole hydrazide compound can be used as integrin avβ3 receptor antagonist. Besides, it has obvious anti-prostate cancer activity and has a significant inhibitory effect on enzalutamide-resistant cell lines. In addition, the above-mentioned compound has obvious anti-tumor angiogenesis activity and can be used in the preparation of anti-tumor angiogenesis drugs to inhibit tumor angiogenesis.

The present invention provides a pharmaceutical composition containing enzalutamide having excellent dissolution and dissolution retention properties, and a method for producing the pharmaceutical composition. [Solution] A pharmaceutical composition containing enzalutamide solid dispersion particles and a cellulose-based polymer.