Antibodies
CO-1686 (AVL-301)
- 貨號 Cat. No.
- S7284
- 規格 Size
- 50mgã€100mg
- 品牌 Brand
- Selleckchem
Description
CO-1686 (AVL-301)
Catalog No.S7284
CO-1686 is an irreversible, mutant-selective EGFR inhibitor with Ki of 21.5 nM and 303.3 nM for EGFRL858R/T790M and EGFRWT, respectively. Phase 1/2.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | CO-1686 is an irreversible, mutant-selective EGFR inhibitor with Ki of 21.5 nM and 303.3 nM for EGFRL858R/T790M and EGFRWT, respectively. Phase 1/2. | |||||
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| Targets | EGFRL858R/T790M | EGFRWT | ||||
| IC50 | 21.5 nM (Ki) | 303.3 nM (Ki)[1] | ||||
| In vitro | CO-1686 inhibits p-EGFR with IC50 ranging from 62 to 187 nM in the mutant EGFR–expressing cells, while inhibits EGFR phosphorylation with IC50 of > 2,000 nM in the three WT EGFR–expressing cells. CO-1686 selectively inhibits growth of NSCLC cells expressing mutant EGFR with GI50 ranging from 7 to 32 nM, and induces apoptosis. CO-1686–resistant NSCLC cell lines exhibits signs of epithelial-mesenchymal transition and increased sensitivity to AKT inhibitors. [1] | |||||
| In vivo | CO-1686 causes dose-dependent and significant tumor growth inhibition in all EGFR-mutant models as well as human EGFRL858R- and EGFRL858R/T790M-expressing transgenic mice. [1] | |||||
| Features | ||||||
Protocol(Only for Reference)
Kinase Assay: [1]
| Inhibition Kinetics Studies | Recombinant human wild-type and T790M/L858R double mutant EGFR, both Nterminal GST-tagged, are used in the assay. The Omnia continuous read assay is performed as described by the vendor. |
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Cell Assay: [1]
| Cell lines | NSCLC cell lines expressing mutant EGFR (HCC827, PC9, HCC827-EPR, and NCI-H1975) and cell lines expressing WT EGFR (A431, NCI-H1299, and NCI-H358) |
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| Concentrations | ~10 μM |
| Incubation Time | 72 hours |
| Method | Cells are seeded at 3,000 cells per well in growth media supplemented with 5% FBS, 2 mmol/L, L-glutamine, and 1% penicillin–streptomycin, allowed to adhere overnight, and treated with a dilution series of test compounds for 72 hours. Cell viability is determined by CellTiter-Glo, and results are represented as background-subtracted relative light units normalized to a dimethyl sulfoxide (DMSO)–treated control. Growth inhibition (GI 50) values are determined by GraphPad Prism 5.04. MK-2206 and XL-880 compounds are obtained from Selleck Chemical. CI data are generated using CalcuSyn. |
Animal Study: [1]
| Animal Models | Human EGFRL858R- and EGFRL858R/T790M-expressing transgenic mice. |
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| Dosages | ~50 mg/kg |
| Administration | Oral gavage |
| Solubility | 1% DMSO/30% polyethylene glycol/1% Tween 80, 30 mg/mL |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01526928 | Recruiting | Locally Advanced or Metastatic Non-small Cell Lung Cancer. | Clovis Oncology, Inc. | 2012-03 | Phase 1|Phase 2 |
Chemical Information
Download CO-1686 (AVL-301) SDF
| Molecular Weight (MW) | 555.55 |
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| Formula | C27H28F3N7O3 |
| CAS No. | 1374640-70-6 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | CNX-419, AVL-301 |
| Solubility (25°C) * | In vitro | DMSO | 100 mg/mL (180 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | <1 mg/mL (<1 mM) | ||
| In vivo | 1% DMSO/30% polyethylene glycol/1% Tween 80, | 30 mg/mL | |
| * <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. | |||
| Chemical Name | 2-​Propenamide, N-​[3-​[[2-​[[4-​(4-​acetyl-​1-​piperazinyl)​-​2-​methoxyphenyl]​amino]​-​5-(trifluoromethyl)​-​4-​pyrimidinyl]​amino]​phenyl]​- |
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