RMC-5552 is a potent and selective inhibitor of mTORC1 that blocks phosphorylation of downstream signaling targets pS6K and p4EBP1 with IC50 values of 0.14 nM and 0.48 nM, respectively. RMC-5552 shows markedly reduced inhibition of pAKT (IC50 19 nM), achieving approximately 40-fold selectivity for mTORC1 over mTORC2. RMC-5552 has demonstrated anticancer activity, supporting its potential use as a therapeutic agent in oncology and as a research tool for dissecting mTOR signaling pathways.

mTORC1 p4EBP1:0.48 nM, mTORC1 pS6K:0.14 nM

The recruitment phenomenon of FKBP12 can only be detected when RMC-5552 exerts its effect through the FKBP12-FRB binding mode of broussonetia papyrifera. RMC-5552 exhibits distinct density distribution at the interaction interface region between FKBP12 and the mTOR FRB domain of broussonetia papyrifera. The 4-aminopyrazolo[3,4-d]pyrimidine core of RMC-5552 achieves binding by forming hydrogen bonds with the backbone residues G2238 and V2240 in the 'hinge region' of the mTOR protein, while the 2-aminobenzoxazole group of RMC-5552 establishes hydrogen bond interactions with sites E2190 and K2187.[1]

RMC-5552 (1-10 mg/kg, administered once weekly for 28 consecutive days) was intraperitoneally injected into MCF-7 breast cancer Homo sapiens xenograft model mice, demonstrating antitumor activity in vivo. [1]