8skl

Publication Abstract from PubMed

The inhibition of protein tyrosine phosphatases 1B (PTP1B) and N2 (PTPN2) has emerged as an exciting approach for bolstering T cell anti-tumor immunity. ABBV-CLS-484 is a PTP1B/PTPN2 inhibitor in clinical trials for solid tumors. Here we have explored the therapeutic potential of a related small-molecule-inhibitor, Compound-182. We demonstrate that Compound-182 is a highly potent and selective active site competitive inhibitor of PTP1B and PTPN2 that enhances T cell recruitment and activation and represses the growth of tumors in mice, without promoting overt immune-related toxicities. The enhanced anti-tumor immunity in immunogenic tumors can be ascribed to the inhibition of PTP1B/PTPN2 in T cells, whereas in cold tumors, Compound-182 elicited direct effects on both tumor cells and T cells. Importantly, treatment with Compound-182 rendered otherwise resistant tumors sensitive to alpha-PD-1 therapy. Our findings establish the potential for small molecule inhibitors of PTP1B and PTPN2 to enhance anti-tumor immunity and combat cancer.

A small molecule inhibitor of PTP1B and PTPN2 enhances T cell anti-tumor immunity.,Liang S, Tran E, Du X, Dong J, Sudholz H, Chen H, Qu Z, Huntington ND, Babon JJ, Kershaw NJ, Zhang ZY, Baell JB, Wiede F, Tiganis T Nat Commun. 2023 Jul 27;14(1):4524. doi: 10.1038/s41467-023-40170-8. PMID:37500611^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.