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MedKoo Cat#: 205020 | Name: Crenolanib
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Crenolanib is an orally bioavailable small molecule, targeting the platelet-derived growth factor receptor (PDGFR), with potential antineoplastic activity. Crenolanib binds to and inhibits PDGFR, which may result in the inhibition of PDGFR-related signal transduction pathways, and, so, the inhibition of tumor angiogenesis and tumor cell proliferation.

Chemical Structure

Crenolanib
Crenolanib
CAS#670220-88-9 (free base)

Theoretical Analysis

MedKoo Cat#: 205020

Name: Crenolanib

CAS#: 670220-88-9 (free base)

Chemical Formula: C26H29N5O2

Exact Mass: 443.2321

Molecular Weight: 443.54

Elemental Analysis: C, 70.41; H, 6.59; N, 15.79; O, 7.21

Price and Availability

Size Price Availability Quantity
10mg USD 350.00 2 Weeks
25mg USD 650.00 2 Weeks
50mg USD 1,050.00 2 Weeks
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Related CAS #
670220-93-6 (besylate) 670220-88-9 (free base)
Synonym
CP 868596; CP868596; CP-868596; ARO 002; ARO-002; ARO002; Crenolanib.
IUPAC/Chemical Name
1-(2-(5-((3-methyloxetan-3-yl)methoxy)-1H-benzo[d]imidazol-1-yl)quinolin-8-yl)piperidin-4-amine.
InChi Key
DYNHJHQFHQTFTP-UHFFFAOYSA-N
InChi Code
InChI=1S/C26H29N5O2/c1-26(14-32-15-26)16-33-20-6-7-22-21(13-20)28-17-31(22)24-8-5-18-3-2-4-23(25(18)29-24)30-11-9-19(27)10-12-30/h2-8,13,17,19H,9-12,14-16,27H2,1H3
SMILES Code
NC1CCN(C2=C3N=C(N4C=NC5=CC(OCC6(C)COC6)=CC=C45)C=CC3=CC=C2)CC1
Appearance
Solid powder
Purity
>95% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>5 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Crenolanib is an investigational new drug being developed by AROG Pharmaceuticals, LLC for the treatment of certain types of cancer. Crenolanib is a tyrosine kinase inhibitor that acts by specifically inhibiting the receptor tyrosine kinases PDGFRA and PDGFRB. Crenolanib is an orally bioavailable, selective small molecule inhibitor of the Platelet-derived growth factor receptor PDGFR) tyrosine kinase, inhibiting both PDGFRA and PDGFRB at picomolar concentrations.  Type III receptor tyrosine kinases (RTK), including c-KIT, PDGFRα and PDGFRβ, have been directly implicated in the pathogenesis of epithelial, mesenchymal, and hematological malignancies.[1] The PDGF/PDGFR pathway is the primary driver of oncogenesis in several malignancies including gastrointestinal stromal tumor (GIST),[2] both adult[3] and pediatric gliomas,[4] as well as a subset of Non-small-cell lung carcinoma (NSCLC).[5] These malignancies often respond to treatment with non-selective inhibitors of PDGFR like imatinib and sunitinib. Crenolanib is a 100-500-fold more potent inhibitor of PDGFRα and PDGFRβ than other commercially available TKIs. It is currently being developed as an antineoplastic agent in cancers. (source: http://en.wikipedia.org/wiki/ Crenolanib ).       
Product Data
Product Data
Certificate of Analysis
View CoA: current batch, Lot#C21M07C15
Safety Data Sheet (SDS)
View Safety Data Sheet (SDS)
Instruction
View handling instruction
Biological target:
Crenolanib is a potent and selective inhibitor of wild-type and mutant isoforms of the class III receptor tyrosine kinases FLT3 and PDGFRα/β with Kds of 0.74 nM and 2.1 nM/3.2 nM, respectively.
In vitro activity:
Unlike cetuximab, crenolanib remarkably suppressed ERK and AKT/mTOR pathways in HT29 cells with BRAF mutation and in HCT116 cells with KRAS mutation with corresponding growth-suppressing effects. Reference: Mol Cancer Res. 2021 May;19(5):812-822. https://pubmed.ncbi.nlm.nih.gov/33579816/
In vivo activity:
Crenolanib 15 mg/kg was administered intraperitoneally to C57BL/6J mice once daily for 2 weeks. Treatment with crenolanib significantly reduced dermal thickness and collagen content in the back skin of Ang II-challenged mice (Figure 4b–d). Crenolanib also significantly reduced the number of αSMA-positive cells in the upper dermis (Figure 4e). Reference: J Invest Dermatol. 2017 Aug; 137(8): 1671–1681. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560111/
Solvent mg/mL mM
Solubility
DMSO 46.1 103.96
DMF 20.0 45.09
DMF:PBS (pH 7.2) (1:1) 0.5 1.13
Ethanol 8.5 19.16
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 443.54 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Fujino S, Miyoshi N, Ito A, Yasui M, Ohue M, Ogino T, Takahashi H, Uemura M, Matsuda C, Mizushima T, Doki Y, Eguchi H. Crenolanib Regulates ERK and AKT/mTOR Signaling Pathways in RAS/BRAF-Mutated Colorectal Cancer Cells and Organoids. Mol Cancer Res. 2021 May;19(5):812-822. doi: 10.1158/1541-7786.MCR-20-0600. Epub 2021 Feb 12. PMID: 33579816. 2. Kampa-Schittenhelm KM, Frey J, Haeusser LA, Illing B, Pavlovsky AA, Blumenstock G, Schittenhelm MM. Crenolanib is a type I tyrosine kinase inhibitor that inhibits mutant KIT D816 isoforms prevalent in systemic mastocytosis and core binding factor leukemia. Oncotarget. 2017 Aug 7;8(47):82897-82909. doi: 10.18632/oncotarget.19970. PMID: 29137311; PMCID: PMC5669937. 3. Makino K, Makino T, Stawski L, Mantero JC, Lafyatis R, Simms R, Trojanowska M. Blockade of PDGF Receptors by Crenolanib Has Therapeutic Effect in Patient Fibroblasts and in Preclinical Models of Systemic Sclerosis. J Invest Dermatol. 2017 Aug;137(8):1671-1681. doi: 10.1016/j.jid.2017.03.032. Epub 2017 Apr 19. PMID: 28433542; PMCID: PMC5560111. 4. Wang P, Song L, Ge H, Jin P, Jiang Y, Hu W, Geng N. Crenolanib, a PDGFR inhibitor, suppresses lung cancer cell proliferation and inhibits tumor growth in vivo. Onco Targets Ther. 2014 Sep 26;7:1761-8. doi: 10.2147/OTT.S68773. PMID: 25328409; PMCID: PMC4196792.
In vitro protocol:
1. Fujino S, Miyoshi N, Ito A, Yasui M, Ohue M, Ogino T, Takahashi H, Uemura M, Matsuda C, Mizushima T, Doki Y, Eguchi H. Crenolanib Regulates ERK and AKT/mTOR Signaling Pathways in RAS/BRAF-Mutated Colorectal Cancer Cells and Organoids. Mol Cancer Res. 2021 May;19(5):812-822. doi: 10.1158/1541-7786.MCR-20-0600. Epub 2021 Feb 12. PMID: 33579816. 2. Kampa-Schittenhelm KM, Frey J, Haeusser LA, Illing B, Pavlovsky AA, Blumenstock G, Schittenhelm MM. Crenolanib is a type I tyrosine kinase inhibitor that inhibits mutant KIT D816 isoforms prevalent in systemic mastocytosis and core binding factor leukemia. Oncotarget. 2017 Aug 7;8(47):82897-82909. doi: 10.18632/oncotarget.19970. PMID: 29137311; PMCID: PMC5669937.
In vivo protocol:
1. Makino K, Makino T, Stawski L, Mantero JC, Lafyatis R, Simms R, Trojanowska M. Blockade of PDGF Receptors by Crenolanib Has Therapeutic Effect in Patient Fibroblasts and in Preclinical Models of Systemic Sclerosis. J Invest Dermatol. 2017 Aug;137(8):1671-1681. doi: 10.1016/j.jid.2017.03.032. Epub 2017 Apr 19. PMID: 28433542; PMCID: PMC5560111. 2. Wang P, Song L, Ge H, Jin P, Jiang Y, Hu W, Geng N. Crenolanib, a PDGFR inhibitor, suppresses lung cancer cell proliferation and inhibits tumor growth in vivo. Onco Targets Ther. 2014 Sep 26;7:1761-8. doi: 10.2147/OTT.S68773. PMID: 25328409; PMCID: PMC4196792.
1: Zhao JC, Agarwal S, Ahmad H, Amin K, Bewersdorf JP, Zeidan AM. A review of FLT3 inhibitors in acute myeloid leukemia. Blood Rev. 2022 Mar;52:100905. doi: 10.1016/j.blre.2021.100905. Epub 2021 Nov 3. PMID: 34774343; PMCID: PMC9846716. 2: Wu M, Li C, Zhu X. FLT3 inhibitors in acute myeloid leukemia. J Hematol Oncol. 2018 Dec 4;11(1):133. doi: 10.1186/s13045-018-0675-4. PMID: 30514344; PMCID: PMC6280371. 3: Fujino S, Miyoshi N, Ito A, Yasui M, Ohue M, Ogino T, Takahashi H, Uemura M, Matsuda C, Mizushima T, Doki Y, Eguchi H. Crenolanib Regulates ERK and AKT/mTOR Signaling Pathways in RAS/BRAF-Mutated Colorectal Cancer Cells and Organoids. Mol Cancer Res. 2021 May;19(5):812-822. doi: 10.1158/1541-7786.MCR-20-0600. Epub 2021 Feb 12. PMID: 33579816. 4: Bisbee C, Campagne O, Gajjar A, Tinkle CL, Stewart CF. Population pharmacokinetics of crenolanib in children and young adults with brain tumors. Cancer Chemother Pharmacol. 2022 Apr;89(4):459-468. doi: 10.1007/s00280-022-04412-8. Epub 2022 Feb 25. PMID: 35212779; PMCID: PMC8957602. 5: Reichert D, Adolph L, Köhler JP, Buschmann T, Luedde T, Häussinger D, Kordes C. Improved Recovery from Liver Fibrosis by Crenolanib. Cells. 2021 Apr 4;10(4):804. doi: 10.3390/cells10040804. PMID: 33916518; PMCID: PMC8067177. 6: Heinrich MC, 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. doi: 10.1158/1078-0432.CCR-12-0625. Epub 2012 Jun 27. PMID: 22745105. 7: Galanis A, 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. doi: 10.1182/blood-2013-10-529313. Epub 2013 Nov 13. PMID: 24227820; PMCID: PMC3879910. 8: Smith CC, Lasater EA, Lin KC, Wang Q, McCreery MQ, Stewart WK, Damon LE, Perl AE, Jeschke GR, Sugita M, Carroll M, Kogan SC, Kuriyan J, Shah NP. Crenolanib is a selective type I pan-FLT3 inhibitor. Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5319-24. doi: 10.1073/pnas.1320661111. Epub 2014 Mar 12. PMID: 24623852; PMCID: PMC3986131. 9: Moy RH, Greally M, Chou JF, Li J, Desai AM, Chalasani SB, Won E, Kelsen DP, Ilson DH, Janjigian YY, Capanu M, Ku GY. Phase I/Ib study of crenolanib with ramucirumab and paclitaxel as second-line therapy for advanced esophagogastric adenocarcinoma. Cancer Chemother Pharmacol. 2022 Feb;89(2):255-265. doi: 10.1007/s00280-021-04384-1. Epub 2022 Jan 23. PMID: 35066693. 10: Zimmerman EI, Turner DC, Buaboonnam J, Hu S, Orwick S, Roberts MS, Janke LJ, Ramachandran A, Stewart CF, Inaba H, Baker SD. Crenolanib is active against models of drug-resistant FLT3-ITD-positive acute myeloid leukemia. Blood. 2013 Nov 21;122(22):3607-15. doi: 10.1182/blood-2013-07-513044. Epub 2013 Sep 17. PMID: 24046014; PMCID: PMC3837509. 11: Antar AI, Otrock ZK, Jabbour E, Mohty M, Bazarbachi A. FLT3 inhibitors in acute myeloid leukemia: ten frequently asked questions. Leukemia. 2020 Mar;34(3):682-696. doi: 10.1038/s41375-019-0694-3. Epub 2020 Jan 9. PMID: 31919472. 12: Chang Y, Zhu D, Guo H, Yin X, Ding K, Li Z. Crenolanib-Derived Probes Suitable for Cell- and Tissue-Based Protein Profiling and Single-Cell Imaging. Chembiochem. 2019 Jul 15;20(14):1783-1788. doi: 10.1002/cbic.201900067. Epub 2019 Jul 3. PMID: 30942519. 13: Wang P, Song L, Ge H, Jin P, Jiang Y, Hu W, Geng N. Crenolanib, a PDGFR inhibitor, suppresses lung cancer cell proliferation and inhibits tumor growth in vivo. Onco Targets Ther. 2014 Sep 26;7:1761-8. doi: 10.2147/OTT.S68773. PMID: 25328409; PMCID: PMC4196792. 14: Zhang H, Savage S, Schultz AR, Bottomly D, White L, Segerdell E, Wilmot B, McWeeney SK, Eide CA, Nechiporuk T, Carlos A, Henson R, Lin C, Searles R, Ho H, Lam YL, Sweat R, Follit C, Jain V, Lind E, Borthakur G, Garcia-Manero G, Ravandi F, Kantarjian HM, Cortes J, Collins R, Buelow DR, Baker SD, Druker BJ, Tyner JW. Clinical resistance to crenolanib in acute myeloid leukemia due to diverse molecular mechanisms. Nat Commun. 2019 Jan 16;10(1):244. doi: 10.1038/s41467-018-08263-x. PMID: 30651561; PMCID: PMC6335421. 15: Kampa-Schittenhelm KM, Frey J, Haeusser LA, Illing B, Pavlovsky AA, Blumenstock G, Schittenhelm MM. Crenolanib is a type I tyrosine kinase inhibitor that inhibits mutant KIT D816 isoforms prevalent in systemic mastocytosis and core binding factor leukemia. Oncotarget. 2017 Aug 7;8(47):82897-82909. doi: 10.18632/oncotarget.19970. PMID: 29137311; PMCID: PMC5669937. 16: Saleh K, Khalifeh-Saleh N, Kourie HR. Acute myeloid leukemia transformed to a targetable disease. Future Oncol. 2020 May;16(14):961-972. doi: 10.2217/fon-2019-0670. Epub 2020 Apr 16. PMID: 32297538. 17: Fathi AT. Emergence of crenolanib for FLT3-mutant AML. Blood. 2013 Nov 21;122(22):3547-8. doi: 10.1182/blood-2013-10-528992. PMID: 24263951. 18: Tinkle CL, Broniscer A, Chiang J, Campagne O, Huang J, Orr BA, Li X, Patay Z, Zhang J, Baker SJ, Merchant TE, Jain V, Onar-Thomas A, Stewart CF, Wetmore C, Gajjar A. Phase I study using crenolanib to target PDGFR kinase in children and young adults with newly diagnosed DIPG or recurrent high-grade glioma, including DIPG. Neurooncol Adv. 2021 Dec 1;3(1):vdab179. doi: 10.1093/noajnl/vdab179. PMID: 34993482; PMCID: PMC8717895. 19: Berndsen RH, Castrogiovanni C, Weiss A, Rausch M, Dallinga MG, Miljkovic- Licina M, Klaassen I, Meraldi P, van Beijnum JR, Nowak-Sliwinska P. Anti- angiogenic effects of crenolanib are mediated by mitotic modulation independently of PDGFR expression. Br J Cancer. 2019 Jul;121(2):139-149. doi: 10.1038/s41416-019-0498-2. Epub 2019 Jun 25. PMID: 31235865; PMCID: PMC6738084. 20: Zhao J, Song Y, Liu D. Gilteritinib: a novel FLT3 inhibitor for acute myeloid leukemia. Biomark Res. 2019 Sep 11;7:19. doi: 10.1186/s40364-019-0170-2. Erratum in: Biomark Res. 2019 Oct 17;7:21. PMID: 31528345; PMCID: PMC6737601.