| Size | Price | Stock | Qty |
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| 1mg |
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Purity: ≥98%
BMS-906024 is a novel, potent, selective and orally bioavailable Notch receptor inhibitor. Cancers have a tendency to relapse or to become resistant to treatments that once worked. A family of proteins called Notch is implicated in that resistance and in cancer progression more generally. BMS-906024 is in Phase I clinical trials, both alone and in combination with other agents. Patients with colon, lung, breast, and other cancers are receiving intravenous doses of the compound to determine its safety and optimum dose ranges.
| Targets |
Notch1 (IC50 = 1.6 nM); Notch2 (IC50 = 0.7 nM); Notch3 (IC50 = 3.4 nM); Notch4 (IC50 = 3.4 nM)
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| ln Vitro |
All six lung cancer cell lines have lower Notch1 ICD levels when exposed to BMS-906024 (5-100 nM; 72 hours). Hes1 cryopreservation was reported and total Notch1 was unaffected by BMS-906024 at 100 nM [1]. BMS-906024 inhibited triple negative medium (MDA-MB-468) and blank (TALL-1) cells in the experiment at an IC50 of around 4 nM [2]. BMS-906024 (100 nM; for 72 hours) improves paclitaxel Western Blot analysis [1].
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| ln Vivo |
BMS-906024 (8.5 mg/kg; lateral gavage; days 1 to 4 per week for 3 weeks) significantly increased the tumor growth inhibitory effects of paclitaxel (36 mg/kg). BMS-906024 (?IV/PO) has T1/2 of 4.6/5.3 hours, Cmax of 1/0.3 μM, AUC. BMS-906024 enhances paclitaxel-mediated NSCLC cytotoxicity in vivo through a combination of inhibiting proliferation and promoting cell sealing in a p21- and p57-independent manner [1].
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| Enzyme Assay |
Human constructs were generated by PCR using standard molecular biology techniques and verified by sequencing. All constructs were generated in the pCDNA3.1+ Hyg vector (Invitrogen, Carlsbad, CA) and contain an N-terminal signal sequence, Notch coding sequence and a C-terminal c-myc tag (7 copies of EQKLISEEDL). The Notch coding sequence included begins N-terminal to the putative S2 cleavage site and contains the transmembrane and cytoplasmic domains. Coding sequence in the human Notch1 construct includes amino acids 1714-2555 (Accession NP_060087.3); a M1737V mutation within the transmembrane domain was added to suppress internal translation initiation. Coding sequence in the human Notch-2 construct includes amino acids 1645-2471 (Accession NP_077719.2). Coding sequence in the human Notch-3 construct includes amino acids 1622-2321 (Accession NP_000426.2). Coding sequence in the human Notch-4 construct includes amino acids 1415-2003 (Accession NP_004548.3).[2]
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| Cell Assay |
Western Blot analysis [1]
Cell Types: NSCLC cell lines (A549, H358, H1975, H2444, H1792, HCC44) Tested Concentrations: 5, 10, 25, 50, 100 nM Incubation Duration: 72 hrs (hours). Experimental Results: Notch1 ICD levels were diminished in all six lung cancer cell lines tested at concentrations as low as 5 nM, with maximum depletion concentrations of 50-100 nM. |
| Animal Protocol |
Formulation: BMS-906024 was formulated in 10% vitamin E TPGS, 10% ethanol, and 80% PEG300 for in vivo studies.[1]
Animal/Disease Models: 6 to 12 weeks old female NOD scid gamma (NSG) mice with KRAS- and BRAF -WT PDX-T42 xenograft[1] Doses: 8.5 mg/kg Route of Administration: 3.4/1.9 μM[2] hrs (hrs (hours)). po (oral gavage); days 1 to 4 per week for 3 weeks. Experimental Results: Dramatically enhanced the tumor growth inhibitory effect of paclitaxel (36 mg/kg), but had no significant effect on cisplatin (2 mg/kg) treatment. Animal/Disease Models: Mouse[2] Doses: 1 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: intravenous (iv) (iv)injection or oral administration Experimental Results: T1/2 is 4.6/5.3 hrs (hrs (hours)), Cmax is 1/0.3 μM, AUC is 3.4 /1.9 μM • IV/PO hour. |
| References |
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| Additional Infomation |
(2S,3R)-N'-[(3S)-1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]-2,3-bis(3,3,3-trifluoropropyl)butanediamide is a primary carboxamide, a secondary carboxamide and a tertiary carboxamide.
Osugacestat (BMS-906024) has been used in trials studying the treatment of Cancer, Lymphoblastic Leukemia, Acute T-cell, and Precursor T-Cell Lymphoblastic Lymphoma. Osugacestat is a small-molecule gamma secretase (GS) and pan-Notch inhibitor, with potential antineoplastic activity. Upon intravenous administration, osugacestat binds to GS and blocks activation of Notch receptors, which may inhibit the proliferation of tumor cells with an overly-active Notch pathway. The integral membrane protein GS is a multi-subunit protease complex that cleaves single-pass transmembrane proteins, such as Notch receptors, at residues within their transmembrane domains that lead to their activation. Overactivation of the Notch signaling pathway, often triggered by activating mutations, has been correlated with increased cellular proliferation and poor prognosis in certain tumor types. |
| Molecular Formula |
C26H26F6N4O3
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|---|---|
| Molecular Weight |
556.500067234039
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| Exact Mass |
556.19
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| Elemental Analysis |
C, 56.11; H, 4.71; F, 20.48; N, 10.07; O, 8.63
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| CAS # |
1401066-79-2
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| PubChem CID |
66550890
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| Appearance |
Typically exists as White to off-white solids at room temperature
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
726.3±60.0 °C at 760 mmHg
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| Flash Point |
393.0±32.9 °C
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| Vapour Pressure |
0.0±2.4 mmHg at 25°C
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| Index of Refraction |
1.558
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| LogP |
2.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
39
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| Complexity |
916
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CN1C2=CC=CC=C2C(C3=CC=CC=C3)=N[C@H](NC([C@@H]([C@@H](C(N)=O)CCC(F)(F)F)CCC(F)(F)F)=O)C1=O
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| InChi Key |
AYOUDDAETNMCBW-GSHUGGBRSA-N
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| InChi Code |
InChI=1S/C26H26F6N4O3/c1-36-19-10-6-5-9-18(19)20(15-7-3-2-4-8-15)34-22(24(36)39)35-23(38)17(12-14-26(30,31)32)16(21(33)37)11-13-25(27,28)29/h2-10,16-17,22H,11-14H2,1H3,(H2,33,37)(H,35,38)/t16-,17+,22+/m0/s1
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| Chemical Name |
(2R,3S)-N1-((S)-1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-2,3-bis(3,3,3-trifluoropropyl)succinamide
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| Synonyms |
BMS906024; BMS 906024; Osugacestat; BMS 906024; Osugacestat [USAN]; AL101; (2R,3S)-N1-((S)-1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-2,3-bis(3,3,3-trifluoropropyl)succinamide; DRL23N424R; BMS-906024.
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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 |
| 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 : ~9.5 mg/mL (~17.07 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7969 mL | 8.9847 mL | 17.9695 mL | |
| 5 mM | 0.3594 mL | 1.7969 mL | 3.5939 mL | |
| 10 mM | 0.1797 mL | 0.8985 mL | 1.7969 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01292655 | COMPLETED | Drug: BMS-906024 | Cancer | Bristol-Myers Squibb | 2011-03-03 | Phase 1 |
| NCT01363817 | COMPLETED | Drug: BMS-906024 Drug: Dexamethasone |
Lymphoblastic Leukemia, Acute T-cell Precursor T-Cell Lymphoblastic Lymphoma |
Bristol-Myers Squibb | 2011-09-28 | Phase 1 |
| NCT01653470 | COMPLETED | Drug: Paclitaxel Drug: 5-Fluorouracil (5FU) Drug: Carboplatin |
Cancer | Bristol-Myers Squibb | 2012-10-12 | Phase 1 |
| NCT04973683 | RECRUITING | Drug: AL101 Procedure: Therapeutic Conventional Surgery |
Adenoid Cystic Carcinoma Metastatic Adenoid Cystic Carcinoma |
M.D. Anderson Cancer Center | 2021-09-30 | Phase 1 |
| NCT03691207 | COMPLETEDWITH RESULTS | Drug: AL101 | Adenoid Cystic Carcinoma | Ayala Pharmaceuticals, Inc, | 2018-12-14 | Phase 2 |
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