osunprotafib

Osunprotafib (ABBV-CLS-484) is a first-in-class, potent, orally bioavailable small molecule inhibitor of the protein tyrosine phosphatases **PTPN1** (PTP1B) and **PTPN2** (TCPTP). Developed through a collaboration between **AbbVie** and **Calico Life Sciences**, it acts as an immunotherapy adjuvant by blocking the negative regulation of the JAK-STAT signaling pathway. By inhibiting these phosphatases, osunprotafib enhances the activation and effector function of T cells (specifically increasing STAT1, STAT3, and STAT5 signaling), thereby promoting anti-tumor immunity and potentially overcoming T-cell exhaustion in the tumor microenvironment. Beyond its role in immuno-oncology, the drug exhibits direct anti-tumor activity in specific hematological malignancies, such as ALK-positive anaplastic large cell lymphoma (ALCL) and B-cell acute lymphoblastic leukemia (B-ALL), by inducing oncogenic stress through the hyperactivation of signaling pathways that these cells typically restrain via negative feedback loops. It has been evaluated in Phase 1 clinical trials for advanced solid tumors, including head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC), both as a monotherapy and in combination with PD-1 inhibitors.

Other names

PTPN2/PTPN1 inhibitorPTPN2 inhibitorPTPN-2 inhibitorPTPN 2 inhibitorPTPN1 inhibitorPTPN-1 inhibitorPTPN 1 inhibitor