ABBV-CLS-484 (hydrochloride)

ABBV-CLS-484 is a dual inhibitor of protein tyrosine phosphatase 1N (PTP1N) and PTP2N (IC₅₀s = 2.5 and 1.8 nM, respectively).^[1] It is selective for PTP1N and PTP2N over PTP6N and PTP11N (IC₅₀s = >10 µM for both) but does inhibit PTP9N (IC₅₀ = 15 nM). ABBV-CLS-484 (1 µM) potentiates IFN-γ-induced decreases in the proliferation of B16-F1 mouse melanoma cells. In vivo, ABBV-CLS-484 (20 mg/kg per day), in combination with an anti-PD-L1 antibody, reduces tumor volume in a B16-F1 melanoma murine model. ABBV-CLS-484 alone increases the number of CD8⁺ effector T cells, natural killer (NK) T cells, neutrophils, and monocytes expressing high levels of IFN-γ-induced genes, as well as increases M1 and decreases M2 macrophages, in the tumor microenvironment in the same mouse model when administered at a dose of 20 mg/kg per day.

References:
[1].Baumgartner, C.K., Ebrahimi-Nik, H., Iracheta-Vellve, A., et al.The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunityNature622(7984)850-862(2023).