In this study, we report the development of a novel PARP1/c-Met dual inhibitor derived from the benzofuran-7-carboxamide moiety of the PARP1 inhibitor Mefuparib. Compared with compound 16 obtained in the previous study, compound S12 was identified as a highly potent dual inhibitor with lower molecule weight and better solubility, demonstrating robust inhibitory activity against both PARP1 (IC50 = 21.8 nM) and c-Met (IC50 = 30.2 nM). Importantly, S12 exhibited remarkable anti-tumor efficacy in the HCT116OR xenograft models, suggesting that targeting both PARP1 and c-Met represents an effective therapeutic strategy to overcome PARP1 inhibitor resistance mediated by c-Met amplification.

P1/2, N=74, Recruiting, The First Affiliated Hospital of Zhengzhou University; Shanghai Yidian Pharmaceutical Technology Development Co., Ltd.

P2, N=30, Recruiting, Mayo Clinic | Trial completion date: Dec 2025 --> Sep 2025 | Trial primary completion date: Dec 2025 --> Sep 2025

P2, N=30, Recruiting, Mayo Clinic | Trial completion date: Sep 2025 --> Dec 2025 | Trial primary completion date: Sep 2024 --> Dec 2025

"Foundation Medicine, Inc. today announced that it has received approval from the U.S. Food and Drug Administration (FDA) for FoundationOne Liquid CDx to be used as a companion diagnostic for AKEEGA (niraparib and abiraterone acetate) from Janssen Biotech, Inc, a Johnson & Johnson company, the first and only FDA-approved dual-action tablet combining PARP inhibition and hormone therapy for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC)."

P1, N=23, Completed, Rhizen Pharmaceuticals SA | Active, not recruiting --> Completed

From several possibilities, we chose two conjugates that could be administered intravenously every 2 weeks and maintain TLZ within its known therapeutic window. We describe situations where the PEG∼TLZ conjugates would find utility in humans and suggest how the intravenously administered long-acting prodrugs could in fact be more effective than daily oral administration of free TLZ.

P1, N=23, Active, not recruiting, Rhizen Pharmaceuticals SA | Trial primary completion date: Dec 2023 --> Mar 2024

Our results suggest that ONC201 in combination with TRAIL may be an effective and non-toxic option for the treatment of gastric adenocarcinoma by inducing apoptosis via activation of the ISR, increased cell surface expression of DR5 and down-regulation of inhibitors of apoptosis. Our results demonstrate in vivo anti-tumor effects of ONC201 plus TLY012 against gastric cancer that could be further investigated in clinical trials.

P1/2, N=39, Terminated, Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | N=78 --> 39 | Trial completion date: Apr 2024 --> Jul 2023 | Recruiting --> Terminated | Trial primary completion date: Jan 2024 --> Jul 2023; The sponsor voluntarily terminated the study

P1/2, N=96, Not yet recruiting, Fujian Cancer Hospital