Crenolanib (CP-868596)
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.
- 1. Ivey MJ, Kuwabara JT, et al. "Platelet-derived growth factor receptor-α is essential for cardiac fibroblast survival." Am J Physiol Heart Circ Physiol. 2019 Aug 1;317(2):H330-H344. PMID:31125253
- 2. Tang L, Dai F, et al. "RhoA/ROCK signaling regulates smooth muscle phenotypic modulation and vascular remodeling via the JNK pathway and vimentin cytoskeleton." Pharmacol Res. 2018 May 20;133:201-212. PMID:29791873
| 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. |
| Cell experiment [1,2]: | |
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Cell lines |
EOL-1 cell line, BaF3 cells, H1703 non-small cell lung cancer cell line |
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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. |
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Reacting condition |
50 nM, 48 h |
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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]: | |
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Animal models |
A549 cells xenograft mouse model |
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Dosage form |
10 mg/kg and 20 mg/kg, 2 weeks |
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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. |
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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. |
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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. | |
| 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 (Kd) | 3.2 nM (Kd) | ||||
Quality Control & MSDS
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