CID-1067700

CID-1067700 (ML282) is a pan GTPase inhibitor, and competitively inhibits Ras-related in brain 7 (Rab7) with a K_i of 13 nM. IC50 & Target: Ki: 13 nM (Rab7)^[1] In Vitro: CID-1067700 (ML282) is a pan GTPase inhibitor, and competitively inhibits Rab7 with a K_i of 13 nM. CID-1067700 shows inhibitory activity against nucleotide binding by Rab7, with K_ds of 100 nM and 40 nM for BODIPY-GTP and BODIPY-GDP, respectively. With increasing concentration, CID-1067700 causes strong inhibition on binding of the BODIPY-linked nucleotides, with EC₅₀ values of 11.22 ± 1.34 nM for BODIPY-GTP and 20.96 ± 1.34 nM for BODIPY-GDP and calculated K_i values of 12.89 nM and 19.70 nM respectively. CID-1067700 (10 μM) has no effect on the rate of release of bound BODIPY-linked nucleotide by wild type Rab7 under equilibrium binding conditions^[1]. CID-1067700 (0-40 μM) inhibits Rab7 activity, NF-κB activation as well as AID induction in B cells. Furthermore, CID-1067700 binds Rab7 with a high affinity (EC₅₀: 10-20 nM), and blocks Class switch DNA recombination (CSR) in B cells via targeting Rab7^[2]. In Vivo: CID-1067700 (ML282; 16 mg/kg, i.p.) prevents disease development in lupus-prone mice by Rab7 inhibition, and reduces IgG-IC deposition in MRL/Fas^lpr/lpr mice. CID-1067700 also targets B cells and specifically impairs the CSR machinery in vivo^[2].