ML-SI3

ML-SI3 is a chemical compound which acts as an "antagonist" (i.e. channel blocker) of the TRPML family of calcium channels, with greatest activity at the TRPML1 channel, although it also blocks the related TRPML2 and TRPML3 channels with lower affinity. It is used for research into the role of TRPML1 and its various functions in lysosomes and elsewhere in the body.[1][2][3][4][5][6][7]

ML-SI3
Identifiers
IUPAC name
  • N-[(1S,2S)-2-[4-(2-methoxyphenyl)piperazin-1-yl]cyclohexyl]benzenesulfonamide
CAS Number
PubChem CID
ChemSpider
Chemical and physical data
FormulaC23H31N3O3S
Molar mass429.58 g·mol−1
3D model (JSmol)
SMILES
  • COC1=CC=CC=C1N2CCN(CC2)[C@H]3CCCC[C@@H]3NS(=O)(=O)C4=CC=CC=C4
InChI
  • InChI=1S/C23H31N3O3S/c1-29-23-14-8-7-13-22(23)26-17-15-25(16-18-26)21-12-6-5-11-20(21)24-30(27,28)19-9-3-2-4-10-19/h2-4,7-10,13-14,20-21,24H,5-6,11-12,15-18H2,1H3/t20-,21-/m0/s1
  • Key:OVTXOMMQHRIKGL-SFTDATJTSA-N

See also

References

  1. Kilpatrick BS, Yates E, Grimm C, Schapira AH, Patel S (October 2016). "Endo-lysosomal TRP mucolipin-1 channels trigger global ER Ca2+ release and Ca2+ influx". Journal of Cell Science. 129 (20): 3859–3867. doi:10.1242/jcs.190322. PMID 27577094.
  2. Li X, Rydzewski N, Hider A, Zhang X, Yang J, Wang W, et al. (April 2016). "A molecular mechanism to regulate lysosome motility for lysosome positioning and tubulation". Nature Cell Biology. 18 (4): 404–17. doi:10.1038/ncb3324. hdl:2027.42/120892. PMID 26950892.
  3. Sahoo N, Gu M, Zhang X, Raval N, Yang J, Bekier M, et al. (May 2017). "2+ Efflux Channel in the Tubulovesicle". Developmental Cell. 41 (3): 262–273.e6. doi:10.1016/j.devcel.2017.04.003. PMID 28486130.
  4. Scotto Rosato A, Montefusco S, Soldati C, Di Paola S, Capuozzo A, Monfregola J, Polishchuk E, Amabile A, Grimm C, Lombardo A, De Matteis MA, Ballabio A, Medina DL (December 2019). "TRPML1 links lysosomal calcium to autophagosome biogenesis through the activation of the CaMKKβ/VPS34 pathway". Nature Communications. 10 (1): 5630. doi:10.1038/s41467-019-13572-w. PMC 6904751. PMID 31822666.
  5. Zhang X, Chen W, Gao Q, Yang J, Yan X, Zhao H, et al. (May 2019). "Rapamycin directly activates lysosomal mucolipin TRP channels independent of mTOR". PLoS Biology. 17 (5): e3000252. doi:10.1371/journal.pbio.3000252. PMC 6528971. PMID 31112550.
  6. Li D, Shao R, Wang N, Zhou N, Du K, Shi J, et al. (March 2020). "Sulforaphane Activates a lysosome-dependent transcriptional program to mitigate oxidative stress". Autophagy: 1–16. doi:10.1080/15548627.2020.1739442. PMC 8078734. PMID 32138578.
  7. Leser C, Keller M, Gerndt S, Urban N, Chen CC, Schaefer M, Grimm C, Bracher F (October 2020). "Chemical and pharmacological characterization of the TRPML calcium channel blockers ML-SI1 and ML-SI3". European Journal of Medicinal Chemistry: 112966. doi:10.1016/j.ejmech.2020.112966.
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