Home Tools
Log in
Cart

Crenolanib

Catalog No. T2677   CAS 670220-88-9
Synonyms: Inhibitor, FLT3, Platelet-derived growth factor receptor, Crenolanib, CD135, CP-868596, PDGFR, CP 868596, ARO 002, Cluster of differentiation antigen 135, Autophagy, CP868596, inhibit, Fms like tyrosine kinase 3

Crenolanib is an orally bioavailable type III tyrosine kinases inhibitor of PDGFRα/β and FLT3 (IC50s: 11, 3.2, and 4 nM).

All products from TargetMol are for Research Use Only. Not for Human or Veterinary or Therapeutic Use.
Crenolanib, CAS 670220-88-9
Please contact us for prices and availability for the specification of product you are interested at.
Product consultation
Get quote
Purity: 98%
Biological Description
Chemical Properties
Storage & Solubility Information
Description Crenolanib is an orally bioavailable type III tyrosine kinases inhibitor of PDGFRα/β and FLT3 (IC50s: 11, 3.2, and 4 nM).
Targets&IC50 FLT3:0.74 nmol/L (Kd), PDGFRα:3.2 nmol/L (Kd), PDGFRβ:2.1 nmol/L (Kd)
In vitro Crenolanib is a specific and potent inhibitor of RTK. The Kd of crenolanib for the wild-type receptors PDGFRA, PDGFRB, and FLT3 was 3.2, 2.1, and 0.74 nmol/L, respectively. In EOL-1 cell line, Crenolanib potently inhibits the kinase activity of the fusion oncogene with IC50 values of 21 nmol/L. In addition, it potently inhibits the proliferation of EOL-1 cells (IC50: 0.2 pmol/L) [1]. Crenolanib is a substrate of ABCB1, as evidenced by approximate five-fold resistance of ABCB1-overexpressing cells to crenolanib, reversal of this resistance by the ABCB1-specific inhibitor PSC-833 and stimulation of ABCB1 ATPase activity by crenolanib. In contrast, crenolanib was not a substrate of ABCG2 or ABCC1. Finally, incubation of the FLT3-ITD AML cell lines MV4-11 and MOLM-14 with crenolanib at a pharmacologically relevant concentration of 500 nM did not induce upregulation of ABCB1 cell surface expression [2]. Crenolanib treatment abolished phosphorylation of FLT3 and ERK in HB119 cells, as well as in the AML-patient–derived FLT3–ITD+ cell line Molm14. Fifty nanomolar crenolanib suppressed phosphorylation of FLT3 in primary isolates, including in leukemic blasts from a quizartinib-resistant patient whose disease had evolved an FLT3–ITD/D835Y mutation [3].
In vivo Crenolanib significantly inhibited the growth of tumor mass, and the strongest inhibitory effect was observed with 20 mg/kg treatment. Crenolanib induced massive apoptosis in tumor cells. Furthermore, the dosage of crenolanib applied was well tolerated by recipient mice. No weight loss was observed during the course of treatment [4]. Correlative data from an ongoing clinical trial demonstrate that acute myeloid leukemia patients can achieve sufficient levels of crenolanib to inhibit both FLT3/ITD and resistance-conferring FLT3/D835 mutants in vivo [5].
Kinase Assay Chinese hamster ovary (CHO) cells were transiently transfected with mutated KIT or PDGFRA cDNA constructs and treated with various concentrations of imatinib or crenolanib as previously described. Experiments involving recombinant DNA were carried out using biosafety level 2 conditions in accordance with published guidelines. Protein lysates from cell lines were prepared and subjected to immunoprecipitation using anti-KIT or anti-PDGFRA antibodies followed by sequential immunoblotting for phospho-KIT and total KIT, or phosphotyrosine or total PDGFRA, respectively, as previously reported. Densitometry was carried out to quantify drug effect using Photoshop 5.1 software, with the level of phospho-KIT or phospho-PDGFRA normalized to total protein. Densitometry and proliferation experimental results were analyzed using Calcusyn 2.1 software to mathematically determine the IC50 values. The Wilcoxon rank sum test was used to compare the IC50 values of imatinib and crenolanib for a given mutation [1].
Cell Research Cells were added to 96-well plates at densities of 20,000 cells per well and incubated with imatinib or 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 [1].
Animal Research A549 cells were injected into the axillary regions of mice (2×10^6 cells/mouse). When the tumor volumes reached 70 mm^3, the mice were randomly allocated to the control group, low-dose crenolanib group (10 mg/kg), or high-dose crenolanib group (20 mg/kg) (n=6 per group). The vehicle for crenolanib treatment consists of 10% 1-methyl-2-pyrrolidinone and 90% polyethylene glycol 300. The tumor size and mouse body weight were measured every other day for about 2 weeks. The tumor volume was calculated as follows: (mm^3) = (width × width × length)/2. After treatment, the mice were euthanized using carbon dioxide, and the tumors were harvested and analyzed [4].
Synonyms Inhibitor, FLT3, Platelet-derived growth factor receptor, Crenolanib, CD135, CP-868596, PDGFR, CP 868596, ARO 002, Cluster of differentiation antigen 135, Autophagy, CP868596, inhibit, Fms like tyrosine kinase 3
Molecular Weight 443.551
Formula C26H29N5O2
CAS No. 670220-88-9

Storage

Powder: -20°C for 3 years

In solvent: -80°C for 2 years

Solubility Information

DMSO: 89 mg/mL (200.65 mM), warmed

Ethanol: 7 mg/mL (15.78 mM)

( < 1 mg/ml refers to the product slightly soluble or insoluble )

Citations

References and Literature
1. Lin Q, Qin M, Zhao S, et al. The roles of PDGFRα signaling in the postnatal development and functional maintenance of the SMC‐ICC‐PDGFRα+ cell (SIP) syncytium in the colon. Neurogastroenterology & Motility. 2019, 31(5): e13568 1. Heinrich MC, et al.Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumors. Clin Cancer Res, 2012, Jun 27. 2. Mathias TJ, et al. The FLT3 and PDGFR inhibitor crenolanib is a substrate of the multidrug resistance protein ABCB1 but does not inhibit transport function at pharmacologically relevant concentrations. Invest New Drugs. 2015 Apr;33(2):300-9. 3. Smith CC, et al. Crenolanib is a selective type I pan-FLT3 inhibitor. Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5319-24. 4. Wang P, et al. Crenolanib, a PDGFR inhibitor, suppresses lung cancer cell proliferation and inhibits tumor growth in vivo. Onco Targets Ther. 2014 Sep 26;7:1761-8. 5. Galanis A, et al. Crenolanib is a potent inhibitor of FLT3 with activity against resistance-conferring point mutants. Blood. 2014 Jan 2;123(1):94-100.

Related compound libraries

This product is contained In the following compound libraries:
Anti-Cancer Compound Library Preclinical Compound Library Autophagy Compound Library Cytokine Inhibitor Library Hematonosis Compound Library Anti-Pancreatic Cancer Compound Library Inhibitor Library Drug-induced Liver Injury (DILI) Compound Library Drug Repurposing Compound Library Anti-Cancer Approved Drug Library

Related Products

Related compounds with same targets
Salinomycin sodium salt Physalin A Latifolin Lup-20(29)-en-28-oic acid R1487 Hydrochloride PTC-209 hydrobromide LYN-1604 ALLO-1

Dose Conversion

You can also refer to dose conversion for different animals. More

In vivo Formulation Calculator (Clear solution)

Step One: Enter information below
Dosage
mg/kg
Average weight of animals
g
Dosing volume per animal
ul
Number of animals
Step Two: Enter the in vivo formulation
% DMSO
%
% Tween 80
% ddH2O
Calculate Reset

Calculator

Molarity Calculator
Dilution Calculator
Reconstitution Calculation
Molecular Weight Calculator
=
X
X

Molarity Calculator allows you to calculate the

  • Mass of a compound required to prepare a solution of known volume and concentration
  • Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Concentration of a solution resulting from a known mass of compound in a specific volume
See Example

An example of a molarity calculation using the molarity calculator
What is the mass of compound required to make a 10 mM stock solution in 10 ml of water given that the molecular weight of the compound is 197.13 g/mol?
Enter 197.13 into the Molecular Weight (MW) box
Enter 10 into the Concentration box and select the correct unit (millimolar)
Enter 10 into the Volume box and select the correct unit (milliliter)
Press calculate
The answer of 19.713 mg appears in the Mass box

X
=
X

Calculator the dilution required to prepare a stock solution

Calculate the dilution required to prepare a stock solution
The dilution calculator is a useful tool which allows you to calculate how to dilute a stock solution of known concentration. Enter C1, C2 & V2 to calculate V1.

See Example

An example of a dilution calculation using the Tocris dilution calculator
What volume of a given 10 mM stock solution is required to make 20ml of a 50 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=50 μM, V2=20 ml and V1 is the unknown:
Enter 10 into the Concentration (start) box and select the correct unit (millimolar)
Enter 50 into the Concentration (final) box and select the correct unit (micromolar)
Enter 20 into the Volume (final) box and select the correct unit (milliliter)
Press calculate
The answer of 100 microliter (0.1 ml) appears in the Volume (start) box

=
/

Calculate the volume of solvent required to reconstitute your vial.

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial.
Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

g/mol

Enter the chemical formula of a compound to calculate its molar mass and elemental composition

Tip: Chemical formula is case sensitive: C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:
To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed n the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

bottom

Tech Support

Please see Inhibitor Handling Instructions for more frequently ask questions. Topics include: how to prepare stock solutions, how to store products, and cautions on cell-based assays & animal experiments, etc.