RMC-6272 (RM-006) is a bi-steric inhibitor that selectively targets mTORC1 with potent inhibition (>10-fold) over mTORC2. Compared to Rapamycin, RMC-6272 shows 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 significantly decreases the kidney tumor burden in Tsc2 +/- A/J mice within four weeks of treatment. When assessed two months post-treatment cessation, the tumor burden remains notably lower in the RMC-6272 group compared to both the Rapamycin and MLN0128 groups[1].