Antibodies
Crenolanib (CP-868596)
- 貨號 Cat. No.
- S2730
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
Crenolanib (CP-868596)
Catalog No.S27301 Product Citations
Crenolanib (CP-868596) is a potent and selective inhibitor of PDGFRα/β with Kd of 2.1 nM/3.2 nM, also potently inhibits FLT3, sensitive to D842V mutation not V561D mutation, >100-fold more selective for PDGFR than c-Kit, VEGFR-2, TIE-2, FGFR-2, EGFR, erbB2, and Src.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | Crenolanib (CP-868596) is a potent and selective inhibitor of PDGFRα/β with Kd of 2.1 nM/3.2 nM, also potently inhibits FLT3, sensitive to D842V mutation not V561D mutation, >100-fold more selective for PDGFR than c-Kit, VEGFR-2, TIE-2, FGFR-2, EGFR, erbB2, and Src. | |||||
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| Targets | PDGFRα | PDGFRβ | ||||
| IC50 | 2.1 nM (Kd) | 3.2 nM (Kd) [1]
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| In vitro | Crenolanib is significantly more potent than imatinib in inhibiting the kinase activity of imatinib-resistant PDGFRα kinases (D842I, D842V, D842Y, D1842-843IM, and deletion I843). Crenolanib is 135-fold more otent than imatinib against D842V in the isogenic model system, with an IC50 of approximately 10 nM. Crenolanib inhibits the kinase activity of the fusion oncogene in EOL-1 cell line, which is derived from a patient with chronic eosinophilic leukemia and expresses the constitutively activated FIP1L1- PDGFRα fusion kinase, with IC50 = 21 nM. Crenolanib also inhibits the proliferation of EOL-1 cells with IC50 = 0.2 pM. Crenolanib inhibits the activation of V561D or D842V-mutant kinases expressed in BaF3 cells with IC50 with 85 nM or 272 nM, respectively. Crenolanib inhibits PDGFRα activation in H1703 non-small cell lung cancer cell line which has 24-fold amplification of the 4q12 region that contains the PDGFRα locus, with IC50 with 26 nM. [1] Crenolanib is an orally bioavailable, highly potent and selective PDGFR TKI. Crenolanib is a benzimidazole compound that has IC50s of 0.9 nM and 1.8 nM for PDGFRA and PDGFRB, respectively. [2] | |||||
| In vivo | ||||||
| Features | ||||||
Protocol(Only for Reference)
Kinase Assay:
| Biochemical Assessment of PDGFRα Kinase Activity | Chinese hamster ovary (CHO) cells are transiently transfected with mutated or wild type PDGFRα constructs and treated with various concentrations of Crenolanib. Experiments involving recombinant DNA are performed using biosafety level 2 conditions in accordance with guidelines. Protein lysates from cell lines are prepared and subjected to immunoprecipitation using anti-PDGFRα antibodies followed by sequential immunoblotting for PDGFRα. Densitometry is performed to quantify drug effect using Photoshop software, with the level of phosphor- PDGFRα normalized to total protein. Densitometry and proliferation experimental results are analyzed using Calcusyn 2.1 software to mathematically determine the IC50 values. The Wilcoxon Rank Sum Test is used to compare the IC50 values of Crenolanib for a given mutation. |
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Cell Assay:
| Cell lines | EOL-1 cell line |
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| Concentrations | 0-20 pM |
| Incubation Time | 72 hours |
| Method | Cells are added to 96-well plates at densities of 20, 000 cells/well and incubated with Crenolanib for 72 hours before measuring cellular proliferation using a 2,3-bis[2-methoxyl-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT)-based assay. |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01393912 | Recruiting | Diffuse Intrinsic Pontine Glioma|Progressive or Refractory High-Grade Glioma | St. Jude Children’s Research Hospital|Arog Pharmaceuticals LLC | 2011-07 | Phase 1 |
| NCT01243346 | Recruiting | D842-related Mutant GIST | Arog Pharmaceuticals LLC | 2011-08 | Phase 2 |
| NCT01229644 | Terminated | Glioma | Arog Pharmaceuticals LLC | 2011-08 | Phase 2 |
| NCT01522469 | Recruiting | Relapsed or Refractory Acute Myeloid Leukemia With FLT3-D835 Activating Mutations | Arog Pharmaceuticals LLC | 2012-07 | Phase 2 |
| NCT01657682 | Recruiting | Acute Myeloid Leukemia With FLT3 Activating Mutations That Has Relapsed or Been Refractory After One or More Prior Therapies | Arog Pharmaceuticals LLC | 2012-10 | Phase 2 |
Chemical Information
Download Crenolanib (CP-868596) SDF
| Molecular Weight (MW) | 443.54 |
|---|---|
| Formula | C26H29N5O2 |
| CAS No. | 670220-88-9 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 89 mg/mL heat (200 mM) |
|---|---|---|---|
| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | 7 mg/mL (15 mM) | ||
| In vivo | 30% PEG400/0.5% Tween80/5% propylene glycol, | 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 | 1-(2-(5-((3-methyloxetan-3-yl)methoxy)-1H-benzo[d]imidazol-1-yl)quinolin-8-yl)piperidin-4-amine |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
|---|---|---|---|---|
| Mass(mg) | 0.44354 | 4.4354 | 8.8708 | 13.3062 |
Product Citations (1)
Large-scale Analysis of PDGFRA Mutations in Melanomas and Evaluation of Their Sensitivity to Tyrosine Kinase Inhibitors Imatinib and Crenolanib. [Dai J, et al. Clin Cancer Res 2013;19(24):6935-42]
PubMed: 24132921
