Crenolanib
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MedKoo CAT#: 205020

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

Description: Crenolanib is a n 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

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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: 443.23213
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
5.0mg USD 195.0 2 Weeks
10.0mg USD 365.0 2 Weeks
20.0mg USD 575.0 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; RO-002; RO002; 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

Product Data:

Certificate of Analysis:

Safety Data Sheet (SDS):

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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 46.11 103.96
DMF 20.0 45.09
DMF:PBS (pH 7.2) (1:1) 0.5 1.13
Ethanol 8.5 19.16

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.

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 1: Michael M, Vlahovic G, Khamly K, Pierce KJ, Guo F, Olszanski AJ. Phase Ib study of CP-868,596, a PDGFR inhibitor, combined with docetaxel with or without axitinib, a VEGFR inhibitor. Br J Cancer. 2010 Nov 9;103(10):1554-61. Epub 2010 Oct 19. PubMed PMID: 20959830; PubMed Central PMCID: PMC2990584.

2: Lewis NL, Lewis LD, Eder JP, Reddy NJ, Guo F, Pierce KJ, Olszanski AJ, Cohen RB. Phase I study of the safety, tolerability, and pharmacokinetics of oral CP-868,596, a highly specific platelet-derived growth factor receptor tyrosine kinase inhibitor in patients with advanced cancers. J Clin Oncol. 2009 Nov 1;27(31):5262-9. Epub 2009 Sep 8. PubMed PMID: 19738123; PubMed Central PMCID: PMC2773478.



Additional Information

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 ).