RMC-6272 (RM-006) is a bi-steric inhibitor that selectively targets mTORC1, displaying potent and selective (> 10-fold) inhibition over mTORC2. Compared to Rapamycin, RMC-6272 demonstrates enhanced inhibition of mTORC1 and induces increased cell death in TSC2 null tumors.

RMC-6272 shows more effective growth inhibition in multiple TSC1 or TSC2 mutant tumor cell lines compared to Rapamycin. RMC-6272 causes a more profound growth inhibition in the TSC1 or TSC2 mutant cells than the wild type cells. RMC-6272 at ~1 nM shows near complete inhibition of p4E-BP1 T37/46 , while inhibition of pS6 S240/244 levels is similar for Rapamycin and RM compounds[1].

RMC-6272 markedly reduces kidney tumor burden in Tsc2 +/- A/J mice after four weeks of treatment. Tumor regrowth is assessed two months after treatment cessation, tumor burden is significantly reduced in the RMC-6272 group as compared to the Rapamycin and MLN0128 groups[1].