| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
BMS-986115 targets gamma-secretase, the enzyme responsible for the proteolytic cleavage of Notch receptors. By inhibiting gamma-secretase, the compound blocks the cleavage and release of the Notch intracellular domain (NICD), which is required for Notch-mediated transcriptional activation. The compound inhibits Notch1 and Notch3 with IC50 values of 7.8 nM and 8.5 nM, respectively. This pan-Notch inhibition disrupts Notch signaling, which is frequently dysregulated in cancer.
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|---|---|
| ln Vitro |
The Notch signaling pathway is efficiently inhibited by BMS-986115 (Example 1) [1].
In vitro, BMS-986115 potently inhibits Notch1 and Notch3 with IC50 values of 7.8 nM and 8.5 nM, respectively. By blocking gamma-secretase activity, the compound prevents the proteolytic processing of Notch receptors and subsequent NICD release. This inhibits Notch-mediated transcription and downstream effects on cell proliferation, survival, and differentiation. The compound is used in cancer research to study Notch signaling. |
| ln Vivo |
In vivo, BMS-986115 is orally bioavailable. It has potential antineoplastic activity in preclinical cancer models. By inhibiting gamma-secretase and pan-Notch signaling, the compound blocks Notch-driven tumor growth and progression. Specific animal study data and dosing regimens are available in the primary literature but are not detailed in the available sources.
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| Enzyme Assay |
Not specifically documented for BMS-986115. For gamma-secretase inhibitors, cell-free enzyme assays typically measure the inhibition of gamma-secretase activity using purified enzyme preparations or membrane fractions and synthetic peptide substrates that mimic the Notch cleavage site. Fluorescence-based or radiolabeled detection methods are used to quantify enzyme activity. IC50 values for Notch1 and Notch3 inhibition are determined from concentration-response curves.
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| Cell Assay |
In vitro cell-based assays for BMS-986115 include assessment of Notch signaling inhibition using reporter cell lines with Notch-responsive reporters. NICD generation and downstream target gene expression can be measured by Western blot or qPCR. Cell proliferation and survival assays in Notch-dependent cancer cell lines evaluate the effects of Notch inhibition on cell growth.
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| Animal Protocol |
In vivo studies with BMS-986115 are conducted in mouse models of Notch-driven cancers. The compound is administered orally due to its oral bioavailability. Endpoints include tumor growth inhibition, assessment of Notch signaling inhibition in tumor tissues (NICD levels, target gene expression), and evaluation of antitumor activity. Dosing regimens are detailed in the primary literature.
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| ADME/Pharmacokinetics |
BMS-986115 is orally bioavailable, indicating favorable oral absorption. As a small molecule, it is suitable for oral administration in preclinical studies. The compound has a purity of 99.90%. Detailed PK parameters such as half-life, Cmax, and AUC are available in the primary literature but are not detailed in the available sources.
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| Toxicity/Toxicokinetics |
Specific toxicity data for BMS-986115 are not provided in the available literature. As a research compound, it is not intended for human therapeutic use. Standard laboratory safety precautions should be followed when handling this compound. The compound is supplied for research purposes only.
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| References | |
| Additional Infomation |
BMS-986115 has been used in clinical trials for the treatment of various advanced cancers. Varegacestat is an orally bioavailable γ-secretase (GS) and pan-Notch inhibitor with potential antitumor activity. After administration, Varegacestat binds to GS, blocking the proteolytic cleavage and release of the Notch intracellular domain (NICD). Normally, upon binding of the ligand to the extracellular domain of the Notch receptor, NICD proteolytic cleavage and release occur. This prevents the subsequent translocation of NICD to the nucleus to form a transcription factor complex and also inhibits the expression of Notch-regulated genes. Ultimately, this leads to Notch overexpression and tumor cell apoptosis and growth inhibition. Overexpression of the Notch signaling pathway plays an important role in tumor cell proliferation and survival. The integrated membrane protein GS is a multi-subunit protease complex that cleaves residues within the transmembrane domain of single-transmembrane proteins (such as the Notch receptor), thereby activating these proteins.
BMS-986115 is also known as Notch inhibitor 1 and has the UNII identifier LSK1L593UU. It is an orally bioavailable, gamma-secretase and pan-Notch inhibitor with potential antineoplastic activity. The compound binds to gamma-secretase and blocks NICD release. It is used in cancer research. |
| Molecular Formula |
C26H25F7N4O3
|
|---|---|
| Molecular Weight |
574.490530729294
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| Exact Mass |
574.181
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| CAS # |
1584647-27-7
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| PubChem CID |
73388393
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| Appearance |
White to off-white solid powder
|
| LogP |
4.8
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| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
9
|
| Heavy Atom Count |
40
|
| Complexity |
956
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
FC(CC[C@@H](C(N[C@@H]1C(NC2C(C)=CC=CC=2C(C2C=CC=C(C=2)F)=N1)=O)=O)[C@@H](C(N)=O)CCC(F)(F)F)(F)F
|
| InChi Key |
SRJNRAQUSAVENA-GSHUGGBRSA-N
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| InChi Code |
InChI=1S/C26H25F7N4O3/c1-13-4-2-7-18-19(13)36-24(40)22(35-20(18)14-5-3-6-15(27)12-14)37-23(39)17(9-11-26(31,32)33)16(21(34)38)8-10-25(28,29)30/h2-7,12,16-17,22H,8-11H2,1H3,(H2,34,38)(H,36,40)(H,37,39)/t16-,17+,22+/m0/s1
|
| Chemical Name |
(2S,3R)-N'-[(3S)-5-(3-fluorophenyl)-9-methyl-2-oxo-1,3-dihydro-1,4-benzodiazepin-3-yl]-2,3-bis(3,3,3-trifluoropropyl)butanediamide
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| Synonyms |
BMS986115; BMS 986115; BMS-986115
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~13.12 mg/mL (~22.84 mM ()
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 1.31 mg/mL (2.28 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 13.1 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: 1.31 mg/mL (2.28 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 13.1 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 1.31 mg/mL (2.28 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7407 mL | 8.7034 mL | 17.4067 mL | |
| 5 mM | 0.3481 mL | 1.7407 mL | 3.4813 mL | |
| 10 mM | 0.1741 mL | 0.8703 mL | 1.7407 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.
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