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25mg |
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CB-103 is a novel and potent γ-secretase inhibitor that is currently being investigated in Phase-1 dose escalation in cancer patients. CB-103 produces Notch loss-of-function phenotypes in flies and mice and inhibits the growth of human breast cancer and leukemia xenografts, notably without causing the dose-limiting intestinal toxicity associated with other Notch inhibitors.
ln Vitro |
Limantrafin targets the NOTCH transcriptional activation complex, hence acting as a pan-NOTCH inhibitor [2]. In human T-cell acute lymphoblastic leukemia cancer cell lines, limantripin inhibits NOTCH signaling [2]. Limantrafin has been shown to be effective against tumors in GSI-resistant T-ALL cell lines [2].
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ln Vivo |
In mice, ligandtrafin suppresses cellular processes that are dependent on NOTCH [2]. Limantrafin inhibits the T-ALL PDX model's in vivo growth [2]. Triple-negative breast cancer resistant to GSI/Mab is inhibited in its growth by limantripin (25 mg/kg; ip/po; twice daily; for 2 weeks) [3]. In xenograft models of mouse breast cancers and human T-ALL, limanthin has anti-tumor efficacy [3].
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Cell Assay |
Cell Viability Assay[1]
Cell Types: RPMI 8402, KOPTK1, PANC1, nRas driven melanoma cells Tested Concentrations: 10 μM Incubation Duration: 4 days, 6 days Experimental Results: Resulted in a significant reduction in their growth potential. |
Animal Protocol |
Animal/Disease Models: NSG mice, triple-negative breast cancer mouse xenograft model [3]
Doses: 25 mg/kg Route of Administration: oral/intraperitoneal (ip) injection; 2 times a day; lasted for 2 weeks Experimental Results: Inhibition of GSI/Mab resistance Growth of triple-negative breast cancer. |
References |
[1]. Freddy Radtke, et al. Inhibitors of notch signalling pathway and use thereof in treatment of cancers. US9296682B2.
[2]. R.Lehal, et al. Development of a novel first-in-class oral inhibitor of the NOTCH pathway. [3]. Rajwinder Lehal, et al. Non clinical pharmacology, pharmacokinetics and safety profiling of CB-103: A novel first-in-class small molecule inhibitor of the NOTCH pathway. [4]. Jose Manuel Perez Garcia, et al. First-in-human phase 1-2A study of CB-103, an oral Protein-Protein Interaction Inhibitor targeting pan-NOTCH signalling in advanced solid tumors and blood malignancies. |
Molecular Formula |
C15H18N2O
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Molecular Weight |
242.322
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CAS # |
218457-67-1
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Related CAS # |
CB-103 HCl;218457-67-1;
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SMILES |
O(C1C([H])=C([H])C(=C([H])N=1)N([H])[H])C1C([H])=C([H])C(=C([H])C=1[H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H]
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Chemical Name |
5-Amino-2-(4-tert-butylphenoxy)pyridine
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Synonyms |
CB 103CB-103 CB103
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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 : ~100 mg/mL (~412.68 mM)
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.32 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (10.32 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (8.58 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 4.1268 mL | 20.6339 mL | 41.2677 mL | |
5 mM | 0.8254 mL | 4.1268 mL | 8.2535 mL | |
10 mM | 0.4127 mL | 2.0634 mL | 4.1268 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.