GSM-1 is a potent γ-secretase modulator. GSM-1 directly targets the transmembrane domain of progerin 1 (PS1).

Physicochemical Properties

Molecular Formula	C26H31CLF3NO2
Molecular Weight	481.98
Exact Mass	481.199
CAS #	884600-68-4
Related CAS #	884600-68-4;
PubChem CID	57987388
Appearance	Light yellow to yellow solid powder
Density	1.2±0.1 g/cm3
Boiling Point	547.7±50.0 °C at 760 mmHg
Flash Point	285.0±30.1 °C
Vapour Pressure	0.0±1.5 mmHg at 25°C
Index of Refraction	1.531
LogP	6.96
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	8
Heavy Atom Count	33
Complexity	613
Defined Atom Stereocenter Count	3
SMILES	CC(C)CC[C@H](C1=CC=C(C=C1)Cl)N2CC[C@H](C[C@H]2C3=CC=C(C=C3)C(F)(F)F)CC(=O)O
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
Chemical Name	2-((2S,4R)-1-((R)-1-(4-chlorophenyl)-4-methylpentyl)-2-(4-(trifluoromethyl)phenyl)piperidin-4-yl)acetic acid
Synonyms	GSM-1 GSM 1 (enzyme modulator) J2.559.799K gamma Secretase modulator 1
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	GSM-1 raises the levels of Aβ38 that WT APP produces. Aβ42 levels in WT APP and all Phe mutants are efficiently reduced by 70–80% by GSM-1, even in the case of the V44F mutant, which generates very little Aβ42 [1]. GSM-1 attaches itself directly to PS1's N-terminal segment [2].
References	[1]. Beta-amyloid Precursor Protein Mutants Respond to Gamma-Secretase Modulators. J Biol Chem. 2010 Jun 4;285(23):17798-810. [2]. Phenylpiperidine-type γ-secretase Modulators Target the Transmembrane Domain 1 of Presenilin 1. EMBO J. 2011 Oct 14;30(23):4815-24.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~207.48 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.5 mg/mL (5.19 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.19 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.0748 mL	10.3739 mL	20.7477 mL
	5 mM	0.4150 mL	2.0748 mL	4.1495 mL
	10 mM	0.2075 mL	1.0374 mL	2.0748 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.