abbv-cls 484

Osunprotafib (ABBV-CLS-484) is a potent, orally bioavailable PTP1B/PTPN2 inhibitor in clinical trials for solid tumors. [1] Osunprotafib (ABBV-CLS-484) stimulates the tumor microenvironment and promotes natural killer cell and CD8 T cell function and enhances T cell anti-tumor immunity by enhancing JAK-STAT signaling and reducing T cell dysfunction. [2]

Osunprotafib (ABBV-CLS-484) hydrochloride is an orally active, selective inhibitor targeting the active sites of PTPN1 (IC50: 2.5 nM) and PTPN2 (IC50: 1.8 nM). It shows 6-8 times weaker activity towards PTPN9 and no detectable activity against SHP-1 or SHP-2. This compound enhances the sensitivity of human cancer cell lines to IFNγ. By boosting JAK-STAT signaling and reducing T cell dysfunction, Osunprotafib hydrochloride exhibits potent antitumor immunity.

PTPN2/1-IN-3 (compound 4) is an orally active PTPN2/N1 inhibitor, developed as an improved version of ABBV-CLS-484. It demonstrates antitumor activity, with an IC50 of 9.3 nM for inhibiting PTPN2, and exhibits oral bioavailability of 93% in mice.