Synonym
GSM-1; GSM 1 (enzyme modulator); J2.559.799K; gamma Secretase modulator 1;
IUPAC/Chemical Name
2-((2S,4R)-1-((R)-1-(4-chlorophenyl)-4-methylpentyl)-2-(4-(trifluoromethyl)phenyl)piperidin-4-yl)acetic acid
InChi Key
VMVWLAPASRQXFL-QFWMQHCXSA-N
InChi Code
InChI=1S/C26H31ClF3NO2/c1-17(2)3-12-23(19-6-10-22(27)11-7-19)31-14-13-18(16-25(32)33)15-24(31)20-4-8-21(9-5-20)26(28,29)30/h4-11,17-18,23-24H,3,12-16H2,1-2H3,(H,32,33)/t18-,23-,24+/m1/s1
SMILES Code
O=C(O)C[C@H]1C[C@@H](C2=CC=C(C(F)(F)F)C=C2)N([C@@H](C3=CC=C(Cl)C=C3)CCC(C)C)CC1
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
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
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
Preparing Stock Solutions
The following data is based on the
product
molecular weight
481.98
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 |
1: Ling IF, Golde TE, Galasko DR, Koo EH. Modulation of Aβ42 in vivo by γ-secretase modulator in primates and humans. Alzheimers Res Ther. 2015 Aug 5;7(1):55. doi: 10.1186/s13195-015-0137-y. eCollection 2015. PubMed PMID: 26244059; PubMed Central PMCID: PMC4523931.
2: Pozdnyakov N, Murrey HE, Crump CJ, Pettersson M, Ballard TE, Am Ende CW, Ahn K, Li YM, Bales KR, Johnson DS. γ-Secretase modulator (GSM) photoaffinity probes reveal distinct allosteric binding sites on presenilin. J Biol Chem. 2013 Apr 5;288(14):9710-20. doi: 10.1074/jbc.M112.398602. Epub 2013 Feb 8. PubMed PMID: 23396974; PubMed Central PMCID: PMC3617273.
3: Crump CJ, Fish BA, Castro SV, Chau DM, Gertsik N, Ahn K, Stiff C, Pozdnyakov N, Bales KR, Johnson DS, Li YM. Piperidine acetic acid based γ-secretase modulators directly bind to Presenilin-1. ACS Chem Neurosci. 2011 Dec 21;2(12):705-710. PubMed PMID: 22229075; PubMed Central PMCID: PMC3249837.
4: Ohki Y, Higo T, Uemura K, Shimada N, Osawa S, Berezovska O, Yokoshima S, Fukuyama T, Tomita T, Iwatsubo T. Phenylpiperidine-type γ-secretase modulators target the transmembrane domain 1 of presenilin 1. EMBO J. 2011 Oct 14;30(23):4815-24. doi: 10.1038/emboj.2011.372. PubMed PMID: 22002539; PubMed Central PMCID: PMC3243616.
5: Kretner B, Fukumori A, Gutsmiedl A, Page RM, Luebbers T, Galley G, Baumann K, Haass C, Steiner H. Attenuated Abeta42 responses to low potency gamma-secretase modulators can be overcome for many pathogenic presenilin mutants by second-generation compounds. J Biol Chem. 2011 Apr 29;286(17):15240-51. doi: 10.1074/jbc.M110.213587. Epub 2011 Feb 25. PubMed PMID: 21357415; PubMed Central PMCID: PMC3083200.
6: Page RM, Gutsmiedl A, Fukumori A, Winkler E, Haass C, Steiner H. Beta-amyloid precursor protein mutants respond to gamma-secretase modulators. J Biol Chem. 2010 Jun 4;285(23):17798-810. doi: 10.1074/jbc.M110.103283. Epub 2010 Mar 26. PubMed PMID: 20348104; PubMed Central PMCID: PMC2878544.
