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Chemical Structure| 670220-88-9 Chemical Structure| 670220-88-9

Structure of Crenolanib
CAS No.: 670220-88-9

Chemical Structure| 670220-88-9

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Crenolanib is a potent and selective inhibitor of wild-type and mutant isoforms of class III receptor tyrosine kinases FLT3 and PDGFRα/β with Kds of 0.74 nM and 2.1 nM/3.2 nM, respectively.

Synonyms: CP-868596; CP 868,596; ARO 002

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Product Details of Crenolanib

CAS No. :670220-88-9
Formula : C26H29N5O2
M.W : 443.54
SMILES Code : NC1CCN(C2=C3N=C(N4C=NC5=CC(OCC6(C)COC6)=CC=C45)C=CC3=CC=C2)CC1
Synonyms :
CP-868596; CP 868,596; ARO 002
MDL No. :MFCD21609260
InChI Key :DYNHJHQFHQTFTP-UHFFFAOYSA-N
Pubchem ID :10366136

Safety of Crenolanib

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of Crenolanib

RTK

Isoform Comparison

Biological Activity

Target
  • PDGFRβ

    PDGFRβ, Kd:3.2 nM

  • PDGFRα

    PDGFRα, Kd:2.1 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
Primary human hepatic stellate cells (HSC) 1μM To evaluate the inhibitory effect of Crenolanib on PDGF-BB-induced hepatic stellate cell proliferation Nature. 2019 Nov;575(7783):512-518.
MOLM-13/sor cells 50 nM 24 h Crenolanib induced apoptosis in MOLM-13/sor cells by inhibiting FLT3-ITD and Axl signaling pathways, activating GSK3β and downregulating Mcl-1. Cell Death Discov. 2023 Feb 4;9(1):44.
hepatic stellate cells (HSC) 0.1 µM 72 h Crenolanib significantly inhibited PDGF-BB-mediated HSC proliferation Cells. 2021 Apr 4;10(4):804.
hepatic stellate cells (HSC) 1 µM 7 days Crenolanib treatment induced polygonal cell morphology and lipid accumulation in HSC Cells. 2021 Apr 4;10(4):804.
mouse mammary fibroblasts (MMFs) 1 μM 24 h Inhibition of PDGFRα-D842V mutation significantly diminished Has1 expression in the PDGFRαactivated MMFs, but did not affect Col1a1, Loxl1 and Mmp3. Neoplasia. 2017 Jun;19(6):496-508.
Human brain microvascular ECs 5 nM To study the inhibitory effect of Crenolanib on GBM endothelial cells, results showed that combined use with VEGFR inhibitor Ki8751 inhibited endothelial cell proliferation. Nat Commun. 2018 Aug 27;9(1):3439.
Healthy control and systemic sclerosis (SSc) dermal fibroblasts 100 nM 24 h To investigate the effect of Crenolanib on periostin, CCN2, and type I collagen expression in healthy control and SSc dermal fibroblasts. Results showed that Crenolanib significantly reduced periostin and CCN2 protein expression, but had only modest inhibition on type I collagen. J Invest Dermatol. 2017 Aug;137(8):1671-1681.
Healthy control and systemic sclerosis (SSc) dermal fibroblasts 100 nM 30 min To investigate the effect of Crenolanib on ERK1/2 and Akt phosphorylation in healthy control and SSc dermal fibroblasts. Results showed that Crenolanib effectively inhibited PDGFAA and PDGFBB-induced ERK1/2 and Akt phosphorylation. J Invest Dermatol. 2017 Aug;137(8):1671-1681.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice PDGFR αK mosaic mutant mice Intraperitoneal injection 15mg/kg Once daily for 7 days Crenolanib significantly increased adipogenesis, further supporting the conclusion that PDGFR αK does not erase adipogenic potential. Cell Stem Cell. 2020 May 7;26(5):707-721.e5
NOD-SCID mice MOLM-13/sor xenograft model Oral 10 mg/kg Once daily for 12 days Crenolanib alone was not effective in the MOLM-13/sor xenograft model, and the combination with HHT did not show improvement. Cell Death Discov. 2023 Feb 4;9(1):44.
Rats Thioacetamide (TAA)-induced liver fibrosis model Via drinking water 0.05 mg/L For 2 weeks Crenolanib significantly improved recovery from TAA-induced liver fibrosis Cells. 2021 Apr 4;10(4):804.
Mice RCAS transgenic GBM model Peritoneal injection 50 mg/kg To study the inhibitory effect of Crenolanib on GBM tumor growth, results showed that combined use with Ki8751 significantly prolonged mouse survival and inhibited tumor growth. Nat Commun. 2018 Aug 27;9(1):3439.
Mice Ang II-induced skin and heart fibrosis model Intraperitoneal injection 15 mg/kg Once daily for 2 weeks To evaluate the therapeutic effects of Crenolanib in the Ang II-induced skin and heart fibrosis model. Results showed that Crenolanib significantly reduced skin and heart fibrosis. J Invest Dermatol. 2017 Aug;137(8):1671-1681.

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT01393912 Diffuse Intrinsic Pontine Glio... More >>ma|Progressive or Refractory High-Grade Glioma Less << PHASE1 COMPLETED 2025-10-16 St. Jude Children's Research H... More >>ospital, Memphis, Tennessee, 38105, United States Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.25mL

0.45mL

0.23mL

11.27mL

2.25mL

1.13mL

22.55mL

4.51mL

2.25mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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