| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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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 | |
| Additional Infomation |
CB-103 is under investigation in clinical trial NCT03422679 (Study of CB-103 in Adult Patients With Advanced or Metastatic Solid Tumours and Haematological Malignancies).
Limantrafin is an orally bioavailable protein-protein interaction (PPI) inhibitor that targets the assembly of the NOTCH transcription complex, with potential antineoplastic activity. Upon oral administration, limantrafin targets and inhibits the NOTCH transcriptional activation complex in the cell nucleus. This inhibits the expression of NOTCH target genes and prevents NOTCH signaling, which may inhibit the proliferation of tumor cells mediated by an overly-active Notch pathway. 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 |
C15H18N2O
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|---|---|
| Molecular Weight |
242.322
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| Exact Mass |
242.142
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| Elemental Analysis |
C, 74.35; H, 7.49; N, 11.56; O, 6.60
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| CAS # |
218457-67-1
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| Related CAS # |
CB-103 HCl;218457-67-1;
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| PubChem CID |
2735289
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| Appearance |
White to light brown solid powder
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| Density |
1.09g/cm3
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| Boiling Point |
394.2ºC at 760mmHg
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| Melting Point |
89-90ºC
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| Flash Point |
192.2ºC
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| Vapour Pressure |
2.01E-06mmHg at 25°C
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| Index of Refraction |
1.574
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| LogP |
4.334
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
18
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| Complexity |
254
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| Defined Atom Stereocenter Count |
0
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| SMILES |
0
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| InChi Key |
WHIWGRCYMQLLAO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H18N2O/c1-15(2,3)11-4-7-13(8-5-11)18-14-9-6-12(16)10-17-14/h4-10H,16H2,1-3H3
|
| Chemical Name |
5-Amino-2-(4-tert-butylphenoxy)pyridine
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| Synonyms |
CB 103CB-103 CB103
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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 : ~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.
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