| Identification | Back Directory | [Name]
N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]cyclohexyl}benzenesulfonamide | [MDL Number]
MFCD14811190 | [Molecular Weight]
429.58 |
| Chemical Properties | Back Directory | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 50 mg/mL (116.39 mM; Need ultrasonic) | [form ]
Solid | [color ]
White to off-white | [InChIKey]
OVTXOMMQHRIKGL-UHFFFAOYSA-N | [SMILES]
C1(S(NC2CCCCC2N2CCN(C3=CC=CC=C3OC)CC2)(=O)=O)=CC=CC=C1 |
| Hazard Information | Back Directory | [Uses]
ML-SI3 is a mixture of cis/trans ML-SI3 (HY-139426A), which is a TRPML1/2 channel inhibitor with IC50s of 4.7 μM and 1.7 μM, respectively. ML-SI3 also inhibits lysosomal calcium efflux and blocks downstream TRPML1-mediated autophagy. The cis/trans ML-SI3 (HY-139426A) components of ML-SI3 are TRPML2 activators with EC50s of 3.3 μM and 9.4 μM, respectively[1][2]. | [Biological Activity]
ML-SI3 is a 4-diastereomer racemate (2 cis and 2 trans isomers) with a cation channel TRPML1-blocking (IC50 = 3.1 μM/trans18.5 μM/cis against 5 μM ML-SA1-induced cellular calcium response) and TRPML2-activating activity (EC50 = 3.3 μM/trans9.4 μM/cis)while exhibiting much weaker TRPML3 potency (EC50 = 28.5 μM/transIC50 = 29.0 μM/cis). ML-SI3 is shown to compete against ML-SA1 for binding the same TRPML1 hydrophobic cavity. Comparing with ML-SI1 (GW405833)ML-SI3 is more potent and not agonist-dependenteffectively antagonizing against TRPML1 activation by both MK6-83 and ML-SA1. | [in vivo]
ML-SI3 (1.5 mg/kg, i.p., four times) attenuates I/R injury in mouse cardiomyocytes[6].
| Animal Model: | Myocardial Ischemia/reperfusion (I/R) injury mice[5] | | Dosage: | 1.5 mg/kg | | Administration: | Intraperitoneal injection (i.p.), four times before and during the in vivo I/R (ischemia 30 min and reperfusion 1 day) | | Result: | Restored the blocked autophagic fux in the cardiomyocytes subjected to I/R. |
| [IC 50]
Schistosome; TRPML1: 4.7 μM (IC50); TRPML2: 1.7 μM (IC50); TRPML3: 12.5 μM (IC50) | [References]
[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. 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] Kilpatrick BS, et al. Endo-lysosomal TRP mucolipin-1 channels trigger global ER Ca2+ release and Ca2+ influx. J Cell Sci. 2016 Oct 15;129(20):3859-3867. DOI:10.1242/jcs.190322
[4] Bais S, et al. Schistosome TRPML channels play a role in neuromuscular activity and tegumental integrity. Biochimie. 2022 Mar;194:108-117. DOI:10.1016/j.biochi.2021.12.018
[5] Zhang X, et al. Rapamycin directly activates lysosomal mucolipin TRP channels independent of mTOR. PLoS Biol. 2019 May 21;17(5):e3000252. DOI:10.1371/journal.pbio.3000252
[6] 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. DOI:10.1007/s00395-022-00930-x |
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