| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
γ-Secretase, specifically targeting the transmembrane domain 1 of presenilin 1 (PS1), a catalytic subunit of the γ-secretase complex.
|
|---|---|
| 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].
GSM-1 raises the levels of Aβ38 produced by wild-type APP. It efficiently reduces Aβ42 levels in wild-type APP and all Phe mutants by 70-80%, even in the V44F mutant which generates very little Aβ42. GSM-1 attaches directly to the N-terminal segment of PS1. These effects are observed at low micromolar concentrations in cellular assays. |
| ln Vivo |
In vivo efficacy of GSM-1 has been evaluated in animal models of Alzheimer's disease. The compound modulates amyloid-β peptide production in the brain, reducing Aβ42 levels while increasing Aβ38. Specific dosing regimens, pharmacokinetic parameters, and detailed in vivo results are limited in publicly available literature.
|
| Enzyme Assay |
γ-Secretase modulation is assessed using in vitro enzyme activity assays with purified γ-secretase complex and APP-derived substrates. Aβ peptide production is measured by ELISA or mass spectrometry. Binding to PS1 transmembrane domain is evaluated by surface plasmon resonance or photoaffinity labeling. IC50 and EC50 values are calculated from dose-response curves.
|
| Cell Assay |
Cells expressing wild-type APP or APP mutants are treated with GSM-1 at varying concentrations (typically 0.1-10 μM) for 24-48 hours. Conditioned media is collected and Aβ38, Aβ40, and Aβ42 levels are quantified by ELISA or MSD assays. Intracellular Aβ levels may also be measured. Selectivity for modulation over complete inhibition is assessed.
|
| Animal Protocol |
In vivo studies are conducted in transgenic mouse models of Alzheimer's disease such as APP/PS1 mice. GSM-1 is administered orally or via intraperitoneal injection at various doses. Brain and plasma Aβ levels are measured by ELISA. Pharmacodynamic markers including PS1 interaction and γ-secretase activity are assessed in brain tissue.
|
| ADME/Pharmacokinetics |
GSM-1 has a molecular formula of C26H31ClF3NO2 and molecular weight of 481.98. It is soluble in DMSO (approximately 100 mg/mL). The compound has a predicted logP of 6.96. Storage conditions: powder at -20°C for up to 3 years, in solvent at -80°C for 6 months.
|
| Toxicity/Toxicokinetics |
Specific toxicological data for GSM-1 are limited as it is a research compound. It should be handled with standard laboratory safety precautions. As a γ-secretase modulator rather than inhibitor, GSM-1 is designed to minimize the side effects associated with broad γ-secretase inhibition, such as Notch signaling disruption.
|
| References | |
| Additional Infomation |
GSM-1 is a research tool compound for studying γ-secretase biology and Alzheimer's disease. It is not approved for clinical use. Unlike γ-secretase inhibitors that completely block enzyme activity, GSM-1 modulates Aβ production profile, potentially offering a safer therapeutic approach for Alzheimer's disease by avoiding Notch-related toxicities.
|
| 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)
|
| 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA