Synonym
ML-SI3; ML SI3; MLSI3; ML SI 3; MLSI-3;
IUPAC/Chemical Name
N-(2-[4-(2-Methoxyphenyl)-1-piperazinyl]cyclohexyl)benzenesulfonamide
InChi Key
OVTXOMMQHRIKGL-UHFFFAOYSA-N
InChi Code
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
SMILES Code
O=S(C1=CC=CC=C1)(NC2C(N3CCN(C4=CC=CC=C4OC)CC3)CCCC2)=O
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
To be determined
Shelf Life
>2 years if stored properly
Drug Formulation
To be determined
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
ML-SI3 is a potent TRPML channel inhibitor with IC50s of 4.7 µM and 1.7 µM for TRPML1 and TRPML2, respectively.
In vitro activity:
A cryo-electron microscopy structure of human TRPML1 with ML-SI3 at 2.9-Å resolution was reported. ML-SI3 binds to the hydrophobic cavity created by S5, S6, and PH1, the same cavity where the synthetic agonist ML-SA1 binds. Electrophysiological characterizations show that ML-SI3 can compete with ML-SA1, blocking channel activation yet does not inhibit PI(3,5)P2-dependent activation of the channel.
Reference: Structure. 2021 Nov 4;29(11):1295-1302.e3. https://pubmed.ncbi.nlm.nih.gov/34171299/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
43.0 |
100.10 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
429.58
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Rühl P, Rosato AS, Urban N, Gerndt S, Tang R, Abrahamian C, Leser C, Sheng J, Jha A, Vollmer G, Schaefer M, Bracher F, Grimm C. 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. PMID: 33859333; PMCID: PMC8050276.
2. Schmiege P, Fine M, Li X. Atomic insights into ML-SI3 mediated human TRPML1 inhibition. Structure. 2021 Nov 4;29(11):1295-1302.e3. doi: 10.1016/j.str.2021.06.003. Epub 2021 Jun 24. PMID: 34171299; PMCID: PMC8570993.
In vitro protocol:
1. Rühl P, Rosato AS, Urban N, Gerndt S, Tang R, Abrahamian C, Leser C, Sheng J, Jha A, Vollmer G, Schaefer M, Bracher F, Grimm C. 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. PMID: 33859333; PMCID: PMC8050276.
2. Schmiege P, Fine M, Li X. Atomic insights into ML-SI3 mediated human TRPML1 inhibition. Structure. 2021 Nov 4;29(11):1295-1302.e3. doi: 10.1016/j.str.2021.06.003. Epub 2021 Jun 24. PMID: 34171299; PMCID: PMC8570993.
1: Schmiege P, Fine M, Li X. Atomic insights into ML-SI3 mediated human TRPML1 inhibition. Structure. 2021 Jun 19:S0969-2126(21)00207-0. doi: 10.1016/j.str.2021.06.003. Epub ahead of print. PMID: 34171299.
2: Leser C, Keller M, Gerndt S, Urban N, Chen CC, Schaefer M, Grimm C, Bracher F. 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. Epub 2020 Oct 24. PMID: 33187805.
3: Li D, Shao R, Wang N, Zhou N, Du K, Shi J, Wang Y, Zhao Z, Ye X, Zhang X, Xu H. Sulforaphane Activates a lysosome-dependent transcriptional program to mitigate oxidative stress. Autophagy. 2021 Apr;17(4):872-887. doi: 10.1080/15548627.2020.1739442. Epub 2020 Mar 15. PMID: 32138578; PMCID: PMC8078734.
