Crenolanib (CP-868596)

Catalog No.

A8307

PDGFR-β inhibitor,potent and selective

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Grouped product items
Size	Price	Stock
10mM (in 1mL DMSO)	$120.00	In stock
Evaluation Sample	$30.00	In stock
5mg	$101.00	In stock
25mg	$304.00	In stock

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Background
Product Citation
Chemical Properties
Protocol
Biological Activity
Quality Control

Background

Crenolanib (CP-868596) is a potent, specific, and orally available inhibitor of PDGFRα, PDGFRβ and FLT3 with inhibitor-binding constant (Kd) of 3.2, 2.1, and 0.74 nM, respectively [1].

It has been shown that crenolanib is more potent than quizartinib and sorafenib at blocking FLT3 autophosphorylation and causing cytotoxicity [2]. Crenolanib is confirmed to be100-fold more potent than imatinib at suppressing D842V mutation. In addition, it has been reported that crenolanib inhibits PDGFRα D842V mutation rather than V561D mutation, with IC50 value of 10 nM [1]. In EOL-1 cells, crenolanib also inhibits the FIP1L1-PDGFRA fusion kinase activity (IC50=1 nM) and cell proliferation (IC50= 0.2 pM)[1].

References:
[1] Heinrich MC1, Griffith D, McKinley A, Patterson J, Presnell A, Ramachandran A, Debiec-Rychter M.

Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumors. Clin Cancer Res. 2012 Aug 15;18(16):4375-84.

[2] Galanis A1, Ma H, Rajkhowa T, Ramachandran A, Small D, Cortes J, Levis M. Crenolanib is a potent inhibitor of FLT3 with activity against resistance-conferring point mutants. Blood. 2014 Jan 2;123(1):94-100.

Product Citation

Chemical Properties

Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	443.54
Cas No.	670220-88-9
Formula	C₂₆H₂₉N₅O₂
Synonyms	CP-868596;CP 868596;CP868596
Solubility	≥22.2 mg/mL in DMSO; insoluble in H2O; ≥2.5 mg/mL in EtOH with ultrasonic
Chemical Name	1-[2-[5-[(3-methyloxetan-3-yl)methoxy]benzimidazol-1-yl]quinolin-8-yl]piperidin-4-amine
SDF	Download SDF
Canonical SMILES	CC1(COC1)COC2=CC3=C(C=C2)N(C=N3)C4=NC5=C(C=CC=C5N6CCC(CC6)N)C=C4
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Cell experiment [1,2]:
Cell lines	EOL-1 cell line, BaF3 cells, H1703 non-small cell lung cancer cell line
Preparation method	The solubility of this compound in DMSO is >22.2mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.
Reacting condition	50 nM, 48 h
Applications	In EOL-1 cell line derived from a patient with chronic eosinophilic leukemia and expressed the constitutively activated FIP1L1-PDGFRα fusion kinase, Crenolanib inhibited the kinase activity of the fusion oncogene with IC50 of 21 nM. Crenolanib inhibited the proliferation of EOL-1 cells with IC50 of 0.2 pM. Crenolanib inhibited the activation of V561D or D842V-mutant kinases expressed in BaF3 cells with IC50 of 85 nM or 272 nM, respectively. Crenolanib inhibited PDGFRα activation in H1703 non-small cell lung cancer cell line which has 24-fold amplification of the 4q12 region that contained the PDGFRα locus, with IC50 of 26 nM. Crenolanib (50 nM) decreased A549 NSCLC cell viability, induced apoptosis in A549 NSCLC cells, and inhibited cell migration in A549 NSCLC cells.
Animal experiment [2]:
Animal models	A549 cells xenograft mouse model
Dosage form	10 mg/kg and 20 mg/kg, 2 weeks
Application	Crenolanib (10 mg/kg and 20 mg/kg) suppressed non-small-cell lung cancer tumor growth and induced tumor cell apoptosis, and the dosage of crenolanib applied was well tolerated by recipient mice.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1]. Heinrich M C, Griffith D, McKinley A, et al. Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumors[J]. Clinical cancer research, 2012, 18(16): 4375-4384. [2]. Wang P, Song L, Ge H, et al. Crenolanib, a PDGFR inhibitor, suppresses lung cancer cell proliferation and inhibits tumor growth in vivo[J]. OncoTargets and therapy, 2014, 7: 1761.

Biological Activity

Description	Crenolanib (CP-868596) is a potent and selective inhibitor of PDGFRα/β with Kd of 2.1 nM/3.2 nM.
Targets	PDGFRα	PDGFRβ
IC50	2.1 nM (K_d)	3.2 nM (K_d)