Crenolanib (CP-868596)

For research use only.

Catalog No.S2730 Synonyms: ARO 002

48 publications

Crenolanib (CP-868596) Chemical Structure

CAS No. 670220-88-9

Crenolanib (CP-868596) is a potent and selective inhibitor of PDGFRα/β with Kd of 2.1 nM/3.2 nM in CHO cells, 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. Crenolanib helps to induce mitophagy.

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10mM (1mL in DMSO) EUR 186 In stock
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Selleck's Crenolanib (CP-868596) has been cited by 48 publications

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Biological Activity

Description Crenolanib (CP-868596) is a potent and selective inhibitor of PDGFRα/β with Kd of 2.1 nM/3.2 nM in CHO cells, 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. Crenolanib helps to induce mitophagy.
Targets
FLT3 [1]
(CHO cells)		 PDGFRα [1]
(CHO cells)		 PDGFRβ [1]
(CHO cells)
0.74 nM(Kd) 2.1 nM(Kd) 3.2 nM(Kd)
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]
Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
A549 cells NUfkOmNvS2WubDD2bYFjcWyrdImgZZN{[Xl? MUGzMlkuOTByMDDuUS=> M1vy[FczKGh? M{K2VYEh\G:|ZT3k[ZBmdmSnboSgbY5pcWKrdHnvckBw\iClYX7j[ZIh[2WubDD2bYFjcWyrdIm= MnfqNlU{Ojh2MEm=
MV4-11 MVfGeY5kfGmxbjDhd5NigQ>? MUXhJIRm[3KnYYPlJIlvKG2rdH;jbI9v\HKrYXygcYF1emm6IIDyc5RmcW5iYXPvcol1[XOnIHj5[JJifGG|ZTCyJEhCS09{KR?= NH\neXkzPTN{OESwPS=>

... Click to View More Cell Line Experimental Data
Assay
Methods Test Index PMID
Western blot
pAKT / AKT / pMAPK / MAPK / pSTAT5 / STAT5; 

PubMed: 24227820     


Molm14 cells were treated with the indicated concerntrations of crenolanib for 1 hour and then cells were lysed. Downstream signaling molecules including pAKT, pMAPK, pSTAT5, and the corresponding total protein content were analysed. 

pFLT3 / FLT3 / pERK / ERK / pS6 / S6 ; 

PubMed: 24623852     


Western blot analysis using 4G10 and anti-FLT3 antibody after immunoprecipitation with anti-FLT3 antibody and Western blot analysis of pSTAT5, pERK, anti-STAT5, and anti-ERK antibody performed on whole cell lysates from MV4;11 and Molm14 cells. Cells were exposed to crenolanib for 60 min.

pKIT / KIT ; 

PubMed: 24623852     


(C) Western blot analysis of pKIT (Y703), pERK, pS6, KIT, ERK, and S6 antibody performed on whole cell lysates from HMC 1.2 cells. Cells were exposed to crenolanib for 60 min.

24227820 24623852
Growth inhibition assay
Cell viability; 

PubMed: 24623852     


Normalized cell viability of Molm14, MV4;11, HMC 1.1, HMC 1.2, and K562 cells after 48 h in various concentrations of crenolanib (error bars represent SD of triplicates from the same experiment).

24623852

Protocol

Kinase Assay:

[1]
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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.
Cell Research:

[1]
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  • Cell lines: EOL-1 cell line
  • 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.


    (Only for Reference)

Solubility (25°C)

In vitro DMSO 88 mg/mL warmed (198.4 mM)
Water Insoluble
Ethanol '7 mg/mL
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
30% PEG400+0.5% Tween80+5% propylene glycol
For best results, use promptly after mixing. 		30 mg/mL

* 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 Information

Molecular Weight 443.54
Formula

C26H29N5O2
CAS No. 670220-88-9
Storage powder
in solvent
Synonyms ARO 002
Smiles CC1(COC1)COC2=CC3=C(C=C2)N(C=N3)C4=NC5=C(C=CC=C5N6CCC(CC6)N)C=C4

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT00949624 Completed Drug: CP-868596|Drug: Docetaxel|Drug: AG-013736 Advanced Solid Tumors Arog Pharmaceuticals Inc. December 2005 Phase 1

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID