95 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 invention discloses application of atypical retinoid A-7 in preparation of androgen receptor inhibitors and antitumor drugs, and belongs to the technical field of medicines. It is proved for the first time that AR can be degraded through a CMA pathway, and the atypical retinoid A-7 serving as an AR inhibitor can obviously reduce the AR protein level in prostate cancer cells; in addition, the Atypic retinoids 7 can be used for inhibiting the growth and proliferation capacity of the prostate cancer cells LNCaP; in addition, the invention further provides an anti-tumor medicine composition, the anti-tumor medicine composition comprises the Atypic retinoid-7 and Enzalutamide, and the anti-tumor medicine composition can be used for treating the prostatic cancer and has important clinical significance.

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.

To provide a pharmaceutical tablet containing enzalutamide as an active ingredient which has physical properties that a dissolved state of eluted enzalutamide is maintained for a long period.SOLUTION: A pharmaceutical tablet containing enzalutamide as an active ingredient includes a solid dispersion composition containing enzalutamide and water-soluble polymer carrier, disintegrator, and hydroxypropyl methyl cellulose acetate succinate. By prescribing hydroxypropyl methyl cellulose acetate succinate in combination with solid dispersion containing the active ingredient, the concentration of solution of poorly water soluble enzalutamide can be maintained for a long time.SELECTED DRAWING: None

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 present disclosure discloses application of PRDX5 and GPX4 genes in preparation of drugs for castration-resistant prostate cancer and belongs to the technical field of biological medicines. The present disclosure proposes that silencing or interfering with the expression of the PRDX5 and / or GPX4 genes can be used in the treatment or adjuvant treatment of castration-resistant prostate cancer. The present disclosure proposes for the first time a new strategy for preparing the drugs for the treatment of CRPC using siRNA in combination with an androgen receptor antagonist. The pharmaceutical composition comprising siRNA in combination with an androgen receptor antagonist according to the present disclosure can be used for the treatment of castration-resistant prostate cancer and significantly improves the inhibitory effect of enzalutamide on castration-resistant prostate cancer, which provides the basis for the design and clinical application of nucleic acid drugs with important clinical therapeutic significance.

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 present invention relates to stable pharmaceutical compositions comprising amorphous enzalutamide, and a combination of hypromellose phthalate and cellulose acetate phthalate, wherein the composition exhibits a dissolution rate of less than 15% of drug release in 30 minutes when tested in 300 ml of 0.03N pH 1.2 hydrochloric acid and at least 75% drug release in 90 minutes when tested in 900 ml pH 6.8 phosphate buffer in a USP apparatus Type II at 50 rpm at 37◦C.

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.

Provided herein are methods of treating prostate cancer having at least one pathogenic AR mutation using 7-chloro-2-(4-(3-methoxyazetidin-1-yl)cyclohexyl)-2,4-dimethyl-N-((6-methyl-4-(methylthio)-2-oxo-1,2-dihydropyridin-3-yl)methyl)benzo[d][1,3]dioxole-5-carboxamide, or a pharmaceutically acceptable salt thereof, alone or in combination with a therapeutically effective amount of an androgen receptor signaling inhibitor (ARSI) such as enzalutamide.

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 invention relates to the technical field of cell engineering, in particular to an enzalutamide drug-resistant neuroendocrine prostate cancer cell line and application thereof, the cell line is preserved, and the cell line has a drug-resistant index of 7.18 or above and meets the evaluation standard of a drug-resistant cell line. The application can be used for researching the drug resistance mechanism of the neuroendocrine prostate cancer, evaluating the activity of drugs for resisting the neuroendocrine prostate cancer, preparing a neuroendocrine prostate cancer cell model or preparing a neuroendocrine prostate cancer animal model, and screening and developing drugs for reversing the drug resistance of the neuroendocrine prostate cancer. According to the invention, a new experimental material is provided for the research on the drug resistance of the prostate cancer, and the application has important scientific research value and application prospect. The invention can be used for screening and developing the drug for treating the neuroendocrine prostate cancer and detecting the sensitivity of the drug for resisting the neuroendocrine prostate cancer.

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 invention belongs to the field of biomedicine, and specifically discloses a method for screening a cell line resistant to enzalutamide and an application thereof, comprising the following steps: 1) reviving Lncap cells, and plating cells after the Lncap cells grow to a normal state; 2) after plating the cells, replacing the culture medium with an incomplete culture medium, and starving the Lncap cells; 3) after the starvation treatment, replacing the culture medium with a complete culture medium, and adding testosterone and 0.1-1 mg / mL acetylnitrosourea ENU, and treating for 8-24 hours to induce cell mutation; 4) washing the cells twice with a complete culture medium, and replacing the complete culture medium to continue culturing for more than 24 hours; 5) adding a first concentration of enzalutamide and culturing for one week; 6) using a second concentration of enzalutamide with an increased concentration to culture for one week; 7) using a third concentration of enzalutamide with a further increased concentration to culture for two weeks; 8) after the culture is completed, selecting monoclonal cells for culture amplification, and freezing and preserving; 9) identifying drug resistance to obtain a cell line resistant to enzalutamide.

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.

This disclosure provides a dosage regimen for co-administration of enzalutamide and a strong CYP3A4 inducer.

A lipid nanoparticle (liposome) comprising: (i) an outer shell comprising a lipid formulation; and (ii) one or more therapeutic agents which prevent apoptosis of a target cell is provided. The therape