alphaVbeta1/8 inhibitor PLN-101095

An orally bioavailable, small molecule dual inhibitor of the integrins alpha V beta 1 (aVb1) and 8 (aVb8), with potential immunomodulating and antineoplastic activities. Upon oral administration, alphaVbeta1/8 inhibitor PLN-101095 targets, binds to and inhibits the integrins aVb1 and aVb8 in the tumor microenvironment (TME). This blocks aVb1/8-mediated signaling and prevents the activation of tumor growth factor-beta (TGF-b). Inhibition of TGF-b promotes T-cell infiltration and the release of pro-inflammatory cytokines into the TME, and results in a cytotoxic T lymphocytes (CTLs)-mediated immune response against tumor cells. In addition, this may inhibit the TGF-beta-mediated resistance to checkpoint inhibitors and may sensitize tumors to checkpoint inhibitors. The integrins aVb1 and aVb8 are overexpressed in a variety of tumor types and play a key role in the activation and signaling of TGF-b.