Drug intelligence / Profile preview

HRS-1167 + rifampicin

Development stage
Unknown
Lead developer
Hengrui Pharmaceutical
Modality
Small Molecules
Administration
Oral
01

Overview

**HRS-1167 + rifampicin** is a combination of two pharmaceutical agents: - **HRS-1167 (M9466)** is a next-generation, orally bioavailable small molecule inhibitor selective for Poly (ADP-Ribose) Polymerase 1 (**PARP1**)[1][5]. It exhibits approximately 672-fold selectivity for PARP1 over PARP2, designed to retain strong antitumor efficacy and reduce hematological toxicities compared to first-generation dual PARP1/2 inhibitors[1]. Its mechanism involves catalytic inhibition of PARP1 (via competitive binding to the NAD+ site) as well as potent PARP-DNA trapping, leading to synthetic lethality, particularly in homologous recombination repair (HRR)-deficient tumors such as those with BRCA1/2, PALB2, or RAD51C/D mutations[1][3][5]. Developed initially by Jiangsu Hengrui Pharmaceuticals and co-developed globally by Merck KGaA[1][5], it is under investigation for advanced solid tumors in phase 1/2 clinical trials[3][5]. - **Rifampicin** is a well-established oral antibiotic and potent inducer of cytochrome P450 enzymes, especially CYP3A4, commonly used as a probe for drug-drug interaction studies or as a medication for tuberculosis and other bacterial infections. In combinations, rifampicin can be used to test the pharmacokinetics of investigational agents; it is not cytotoxic nor antitumor by itself in solid tumors[1]. This combination (HRS-1167 + rifampicin) is likely used for **pharmacokinetic and drug-drug interaction studies** involving HRS-1167, rather than as a therapeutic product for disease treatment.

02

Targets

CYP3A4 (Cytochrome P450 3A4)

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