We used known compound UNC2025 as positive control and one million compounds was retrieved from different databases (OTAVA, ZINC, ChEMBL) and docked with MERTK protein...The study finds critical residues which serve a vital part in binding with the inhibitor and the active site of the MERTK protein, i.e., Phe598, Gly599, Lys619, Arg629, Glu633, Glu637, Arg722, Asp723, Arg727, Asp741, Gly743, Leu744, Lys746, Arg758, Ala760, and Lys761 through decomposed binding free energy analysis. This study focuses on the pursuit of several MERTK protein targets, which could have consequences for the development of novel therapeutics for various cancers.

P1, N=83, Terminated, Incyte Corporation | Active, not recruiting --> Terminated; The study was terminated after careful review of the overall clinical activity of this compound and a lack of robust efficacy. The study closure is not based on safety concerns.

P1, N=18, Not yet recruiting, Qurient Co., Ltd.

Furthermore, G-749 is screened and identified as a novel NAT10 inhibitor capable of effectively impeding lysosomal acidification and tumor metastasis by disrupting the NAT10-Ubiquitin-specific Peptidase 39 (USP39) interaction. Overall, the results unveil a novel role of ac4C modifications in regulating lysosomal acidification and propose a potential strategy by targeting NAT10 to inhibit esophageal cancer metastasis.

P1, N=78, Active, not recruiting, Ono Pharmaceutical Co. Ltd | Trial completion date: Oct 2025 --> Apr 2026 | Trial primary completion date: Oct 2025 --> Apr 2026

Lastly, UNC2025-PMAM NPs significantly reduced tumor volume compared to free UNC2025, showing greater therapeutic efficacy in a model of triple-negative breast cancer. These glycopolymer-based, efferocytosis-blocking NPs have promise both as a class of standalone cancer immunotherapy and as an adjuvant to improve response rates to checkpoint immunotherapy.

The ZMYM2-ANXA9 signaling axis drives chemoresistance and tumor progression in CRC. FLT3 inhibition by G749 effectively downregulates ANXA9 and sensitizes tumors to chemotherapy, highlighting a novel therapeutic approach for chemoresistant CRC.

P1, N=88, Terminated, Pfizer | N=67 --> 88 | Trial completion date: Jun 2024 --> Nov 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Jun 2024 --> Nov 2024; Pfizer has made an internal business decision to not continue further development of PF-07265807. This decision was not due to major safety concerns or requests from any regulatory authorities.

P1, N=84, Active, not recruiting, Incyte Corporation | Trial completion date: Apr 2025 --> Sep 2025 | Trial primary completion date: Apr 2025 --> Sep 2025

Pharmacokinetic evaluations and in vivo studies further reveal compound 11 as a promising candidate for further development. Our findings not only advance the understanding of the MerTK-specific mechanism but also propose a strategy for designing selective kinase inhibitors targeting the αC helix conformation.

Targeted knockdown of MerTK or application of UNC2025, a small inhibitor of MerTK, can inhibit DLBCL cell proliferation, promote apoptosis, and inhibit G2/M phase arrest...Therefore, MerTK is ectopically expressed in DLBCL, and targeted inhibition of MerTK suppresses the growth of DLBCL in vitro and in vivo. This study provides clues for precision therapy for DLBCLs that target MerTK.

P1, N=87, Active, not recruiting, Ono Pharmaceutical Co. Ltd | Recruiting --> Active, not recruiting