WO-2026092748-A1 - COMBINED USE OF ANDROGEN SYNTHESIS INHIBITOR AND PARP INHIBITOR FOR TREATING PROSTATE CANCER

Abstract

The combined use of an androgen synthesis inhibitor and a PARP inhibitor for treating prostate cancer. Specifically provided is the use of a compound as represented by formula 1 or a pharmaceutically acceptable salt thereof and an androgen synthesis inhibitor in the preparation of a drug for treating prostate cancer.

Inventors

• WANG, YUTING
• WANG, Quanren

Assignees

• 江苏恒瑞医药股份有限公司
• 上海盛迪医药有限公司

Dates

Publication Date

20260507

Application Date

20251104

Priority Date

20241104

Claims (14)

1. The use of the compound shown in Formula 1 or a pharmaceutically acceptable salt thereof with an inhibitor of androgen synthesis in the preparation of a medicament for treating prostate cancer, preferably wherein the prostate cancer is selected from metastatic prostate cancer.
2. According to the use of claim 1, the prostate cancer is selected from castration-resistant prostate cancer or hormone-sensitive prostate cancer.
3. According to the use described in claim 1 or 2, the prostate cancer is selected from prostate cancer that has failed prior treatment with at least one novel endocrine drug, preferably the novel endocrine drug is selected from abiraterone, enzalutamide, revelutamide, dalotamide, apatamide.
4. For the use according to any one of claims 1-3, wherein the prostate is selected from prostate cancer with a mutation in the HRR-related gene; preferably, the prostate cancer is selected from prostate cancer with at least one mutation in ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2 and RAD51C.
5. The use according to any one of claims 1-4, wherein the androgen synthesis inhibitor is selected from abiraterone or a pharmaceutically acceptable salt thereof, preferably abiraterone acetate.
6. The use according to any one of claims 1-5, wherein the pharmaceutically acceptable salt of the compound represented by Formula 1 is selected from hydrochloride, sulfate, phosphate, methanesulfonate, succinate, fumarate, maleate, p-toluenesulfonate, L-tartrate, D-malate, L-malate and citrate, preferably, the pharmaceutically acceptable salt of the compound represented by Formula 1 is fumarate.
7. According to any one of claims 1-6, the dosage of the compound of formula 1 or its pharmaceutically acceptable salt is selected from 10-300 mg, preferably 10-250 mg, more preferably 10-150 mg, and most preferably 25 mg, 30 mg, 50 mg, 75 mg, or 100 mg.
8. The use according to any one of claims 1-7, wherein the frequency of administration of the compound of formula 1 or its pharmaceutically acceptable salt is selected from once daily, twice daily, or three times daily.
9. According to any one of claims 1-8, the dosage of the androgen synthesis inhibitor is selected from 100-2000 mg, preferably 100-1500 mg, more preferably 100-1000 mg, and most preferably 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, or 1000 mg.
10. The use according to any one of claims 1-9, wherein the frequency of administration of the androgen synthesis inhibitor is selected from once daily, twice daily, or three times daily.
11. The use according to any one of claims 1-10, further comprising use in combination with prednisone or prednisolone.
12. According to the use of claim 11, the dosage of prednisone or prednisolone is selected from 1-20 mg, preferably 1-15 mg, more preferably 1-10 mg, and most preferably 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, or 10 mg.
13. According to the use described in claim 12, the frequency of administration of the prednisone or prednisolone is selected from once daily, twice daily, or three times daily.
14. A pharmaceutical kit comprising a compound of Formula 1 or a pharmaceutically acceptable salt thereof and an inhibitor of androgen synthesis, preferably the compound of Formula 1 or a pharmaceutically acceptable salt thereof and the inhibitor of androgen synthesis are packaged separately.

Description

The combination of androgen synthesis inhibitors and PARP inhibitors is used to treat prostate cancer. Technical Field This disclosure relates to the biopharmaceutical field, specifically to PARP inhibitors and androgen synthesis inhibitors used in the preparation of drugs for the treatment of prostate cancer, and pharmaceutical compositions thereof. Background Technology Poly(ADP-ribose) polymerases (PARPs) are a class of multifunctional protein post-translational modification enzymes widely found in eukaryotic cells, playing important roles in maintaining gene stability and telomere length. The PARP superfamily currently has 17 known members, with only PARP1, PARP2, and PARP3 involved in DNA repair. PARP1 accounts for 80-90% of the PARP family enzyme activity and is a key factor in DNA damage repair. Recent studies have shown that PARP2 inhibition is closely related to hematological toxicity, and the synthetic lethal effects of BRCA mutations are mainly driven by PARP1. Therefore, it can be inferred that developing highly selective PARP1 inhibitors will be beneficial in reducing hematological toxicity and improving the therapeutic index, thus meeting higher clinical treatment needs. Summary of the Invention This disclosure provides the use of PARP inhibitors and androgen synthesis inhibitors in the preparation of medicaments for the treatment of prostate cancer. In some embodiments, the PARP inhibitor is selected from the compounds shown in Formula 1 or their pharmaceutically acceptable salts. In some embodiments, the pharmaceutically acceptable salt of the compound represented by Formula 1 is selected from hydrochloride, sulfate, phosphate, methanesulfonate, succinate, fumarate, maleate, p-toluenesulfonate, L-tartrate, D-malate, L-malate, and citrate. In some specific embodiments, the pharmaceutically acceptable salt of the compound represented by Formula 1 is succinate. In some specific embodiments, the pharmaceutically acceptable salt of the compound represented by Formula 1 is fumarate. In some embodiments, the dosage of the compound of Formula 1 or its pharmaceutically acceptable salt is 10-300 mg. For example, the dosage of the compound of Formula 1 or its pharmaceutically acceptable salt is 10-250 mg, 10-200 mg, 10-150 mg, or 10-100 mg. In some embodiments, the dosage of the compound of Formula 1 or its pharmaceutically acceptable salt is selected from: 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 50 mg, 75 mg, and 100 mg. In some embodiments, the frequency of administration of the compound of Formula 1 or its pharmaceutically acceptable salt is selected from once daily, twice daily, or three times daily. In some embodiments, the frequency of administration of the compound of Formula 1 or its pharmaceutically acceptable salt is selected from once daily. This disclosure also provides a pharmaceutical composition comprising the compound of Formula 1 or a pharmaceutically acceptable salt thereof, and further comprising one or more pharmaceutically acceptable excipients. In some embodiments, the androgen synthesis inhibitor is selected from abiraterone or its pharmaceutically acceptable salts; in some specific embodiments, the androgen synthesis inhibitor is abiraterone acetate. In some embodiments, the dosage of the androgen synthesis inhibitor is selected from 100-2000 mg. In some embodiments, the dosage of the androgen synthesis inhibitor is selected from 100-1500 mg. In some embodiments, the dosage of the androgen synthesis inhibitor is selected from 100-1000 mg. In some embodiments, the dosage of the androgen synthesis inhibitor is selected from 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, and 1000 mg. In a specific implementation plan, the dosage of the androgen synthesis inhibitor is 300 mg. In some embodiments, the frequency of administration of the androgen synthesis inhibitor is selected from once daily, twice daily, or three times daily. In a specific embodiment, the frequency of administration of the androgen synthesis inhibitor is selected from once daily. In a specific embodiment, the frequency of administration of the androgen synthesis inhibitor is selected from twice daily. This disclosure also provides the use of the compound of Formula 1 or a pharmaceutically acceptable salt thereof in combination with an androgen synthesis inhibitor in the preparation of a medicament for treating prostate cancer. This disclosure also provides a compound of Formula 1 or a pharmaceutically acceptable salt thereof used in combination with an androgen synthesis inhibitor for the treatment of prostate cancer. This disclosure also provides a compound of Formula 1 or a pharmaceutically acceptable salt thereof in combination with an inhibitor of androgen synthesis for the treatment of prostate cancer. This disclosure also provides the use of the compound of Formula 1 or a pharmaceutically acceptable salt thereof for the