SIM0501 / Simcere - LARVOL DELTA

USP1 inhibition: A journey from target discovery to clinical translation. (PubMed, Pharmacol Ther) - "RO7623066 (KSQ-4279) reported an acceptable safety profile during a phase I dose escalation study, with anemia being the most common side effect, and demonstrated robust pharmacokinetic, pharmacodynamic, and clinical activity. Other USP1 inhibitors, including SIM0501, XL309-101, and HSK39775, are currently in early clinical development. In this review, we provide an overview of the molecular function of USP1 and its importance as a therapeutic target in oncology, before focusing on the current state of preclinical and clinical development of USP1 inhibitors."

Journal • Review • Hematological Disorders • Oncology • Targeted Protein Degradation • BRCA1 • FANCD2 • FANCI • PCNA • USP1

Synergistic anti-tumor efficacy in olaparib-sensitive and -resistant models via simultaneously inhibition of USP1 and PARP (AACR 2024) - "SIM0501 is a potent, orally bioavailable, specific inhibitor for USP1. Since Ub-PCNA is a direct target of USP1, these results will facilitate the clinical assessment of target engagement by SIM0501. In summary, SIM0501 demonstrates strong synergistic anti-tumor growth effect in combination with PARP inhibitors in both in vitro and in vivo pharmacology studies, which supports the clinical testing of SIM0501, in combination with PARP inhibitors in patients harboring HRR mutations."

Clinical • Late-breaking abstract • Genito-urinary Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • BRCA • BRCA1 • PCNA • USP1

Study of SIM0501 Alone and in Combination in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=176 | Recruiting | Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.

Metastases • Monotherapy • New P1 trial • Oncology • Solid Tumor