2108567-79-7

(rel)-ML-SI3 is one of the active ingredients of ML-SI3 (HY-139426) (another component is (cis)-ML-SI3) that targets three isoforms of TRPML. (rel)-ML-SI3 is an inhibitor of TRPML1 and TRPML3 (IC50=3.1 μM/28.5 μM), and a potent activator of TRPML2 (EC50=3.3 μM)[1][2][3].

TRPML1: 3.1 μM (IC₅₀); TRPML2: 3.3 μM (EC₅₀); TRPML3: 28.5 μM (IC₅₀)

[1] Rühl P, et al. Estradiol analogs attenuate autophagy, cell migration and invasion by direct and selective inhibition of TRPML1, independent of estrogen receptors. Sci Rep. 2021 Apr 15;11(1):8313.??[Content Brief] DOI:10.1038/s41598-021-87817-4
[2] Leser C, et al. Chemical and pharmacological characterization of the TRPML calcium channel blockers ML-SI1 and ML-SI3. Eur J Med Chem. 2021 Jan 15;210:112966. DOI:10.1016/j.ejmech.2020.112966
[3] Xing Y, et al. Blunting TRPML1 channels protects myocardial ischemia/reperfusion injury by restoring impaired cardiomyocyte autophagy. Basic Res Cardiol. 2022 Apr 7;117(1):20.??[Content Brief] DOI:10.1007/s00395-022-00930-x