RMC-4550

**RMC-4550** is a potent, selective, allosteric small-molecule inhibitor of SHP2 (Src homology 2 domain-containing protein tyrosine phosphatase 2), a critical upstream regulator of the RAS/MAPK signaling pathway. Developed by Revolution Medicines, it blocks SHP2's phosphatase activity with an IC50 of approximately 0.6-1.55 nM, demonstrating high selectivity over kinases and other phosphatases. Primarily investigated for **KRAS-mutant cancers** such as pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), and others including colorectal, melanoma, and myeloproliferative neoplasms (MPN), RMC-4550 shows synergistic antitumor effects in combination with ERK inhibitors (e.g., LY3214996), RAS(ON) G12C inhibitors (e.g., RMC-4998), or JAK2 inhibitors (e.g., ruxolitinib). Preclinical data highlight superior MAPK pathway suppression, increased apoptosis, tumor regression in PDAC and NSCLC mouse models, and stimulation of antitumor immunity via enhanced CD8+ T-cell infiltration and macrophage reprogramming, with oral administration and good tolerability.[1][2][3][4][5][7][8][9][10][11]