GDC-1971

RO 749-9790 (also known as GDC-1971 or RG6359) is an orally bioavailable, potent, and selective small molecule allosteric inhibitor of **SHP2** (Src homology region 2 domain-containing phosphatase 2), which is encoded by the **PTPN11** gene. SHP2 is a non-receptor protein tyrosine phosphatase that acts as a critical signaling node downstream of multiple receptor tyrosine kinases (RTKs), facilitating the activation of the RAS/MAPK pathway. By stabilizing SHP2 in its inactive, closed conformation, RO 749-9790 disrupts RAS-mediated signaling, which is frequently hyperactivated in various cancers. Originally discovered by **Relay Therapeutics** as RLY-1971, the compound was licensed to **Roche/Genentech** for clinical development. It is currently being evaluated as a monotherapy and in combination with other targeted agents, such as the KRAS G12C inhibitor divarasib, in patients with advanced or metastatic **solid tumors**, including those enrolled in the tumor-agnostic **TAPISTRY** platform trial.