Home Protein Tyrosine Kinase PDGFR inhibitor - FLT3 inhibitor - Mitophagy activator Crenolanib For research use only.

Crenolanib

Synonyms: CP-868596, ARO 002

Crenolanib is a potent and selective inhibitor of PDGFRα/β with Kd of 2.1 nM/3.2 nM in CHO cells, also potently inhibits FLT3, sensitive to D842V mutation not V561D mutation, >100-fold more selective for PDGFR than c-Kit, VEGFR-2, TIE-2, FGFR-2, EGFR, erbB2, and Src. Crenolanib helps to induce mitophagy.

Crenolanib Chemical Structure

Crenolanib Chemical Structure

CAS No. 670220-88-9

Purity & Quality Control

Crenolanib Related Products

Signaling Pathway

PDGFR Signaling Pathways

PDGFR Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
A549 cells Cell viability assay 3.9-1000 nM 72 h a dose-dependent inhibition of cancer cell viability 25328409
MV4-11 Function assay a decrease in mitochondrial matrix protein aconitase hydratase 2 (ACO2) 25328409
MV4-11 Cytotoxicity assay Cytotoxicity against human MV4-11 cells expressing FLT3 ITD mutant, IC50=0.0015μM 31207462
MOLM13 Cytotoxicity assay Cytotoxicity against human MOLM13 cells expressing FLT3 ITD mutant, IC50=0.0049μM 31207462
MV4-11 Cytotoxicity assay 72 hrs Cytotoxicity in human MV4-11 cells assessed as inhibition of cellular viability incubated for 72 hrs by CellTiter-Blue assay, IC50=0.012μM 30742435
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells 29435139
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells 29435139
MV4-11 Cytotoxicity assay 0.5 to 5000 nM 2 to 8 hrs Cytotoxicity in human MV4-11 cells assessed as inhibition of cellular viability at 0.5 to 5000 nM incubated for 2 to 8 hrs followed by compound washout by CellTiter-Glo luminescent assay 30742435
Click to View More Cell Line Experimental Data

Biological Activity

Description Crenolanib is a potent and selective inhibitor of PDGFRα/β with Kd of 2.1 nM/3.2 nM in CHO cells, also potently inhibits FLT3, sensitive to D842V mutation not V561D mutation, >100-fold more selective for PDGFR than c-Kit, VEGFR-2, TIE-2, FGFR-2, EGFR, erbB2, and Src. Crenolanib helps to induce mitophagy.
Targets
FLT3 [1]
(CHO cells)		 PDGFRα [1]
(CHO cells)		 PDGFRβ [1]
(CHO cells)
0.74 nM(Kd) 2.1 nM(Kd) 3.2 nM(Kd)
In vitro
In vitro

Crenolanib is significantly more potent in inhibiting the kinase activity of resistant PDGFRα kinases (D842I, D842V, D842Y, D1842-843IM, and deletion I843). Crenolanib is more potent against D842V in the isogenic model system, with an IC50 of approximately 10 nM. Crenolanib inhibits the kinase activity of the fusion oncogene in EOL-1 cell line, which is derived from a patient with chronic eosinophilic leukemia and expresses the constitutively activated FIP1L1- PDGFRα fusion kinase, with IC50 = 21 nM. Crenolanib also inhibits the proliferation of EOL-1 cells with IC50 = 0.2 pM. Crenolanib inhibits the activation of V561D or D842V-mutant kinases expressed in BaF3 cells with IC50 with 85 nM or 272 nM, respectively. Crenolanib inhibits PDGFRα activation in H1703 non-small cell lung cancer cell line which has 24-fold amplification of the 4q12 region that contains the PDGFRα locus, with IC50 with 26 nM. [1]

Crenolanib is an orally bioavailable, highly potent and selective PDGFR TKI. Crenolanib is a benzimidazole compound that has IC50s of 0.9 nM and 1.8 nM for PDGFRA and PDGFRB, respectively. [2]
Kinase Assay Biochemical Assessment of PDGFRα Kinase Activity
Chinese hamster ovary (CHO) cells are transiently transfected with mutated or wild type PDGFRα constructs and treated with various concentrations of Crenolanib. Experiments involving recombinant DNA are performed using biosafety level 2 conditions in accordance with guidelines. Protein lysates from cell lines are prepared and subjected to immunoprecipitation using anti-PDGFRα antibodies followed by sequential immunoblotting for PDGFRα. Densitometry is performed to quantify drug effect using Photoshop software, with the level of phosphor- PDGFRα normalized to total protein. Densitometry and proliferation experimental results are analyzed using Calcusyn 2.1 software to mathematically determine the IC50 values. The Wilcoxon Rank Sum Test is used to compare the IC50 values of Crenolanib for a given mutation.
Cell Research Cell lines EOL-1 cell line
Concentrations 0-20 pM
Incubation Time 72 hours
Method

Cells are added to 96-well plates at densities of 20, 000 cells/well and incubated with 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.
Experimental Result Images Methods Biomarkers Images PMID
Western blot pAKT / AKT / pMAPK / MAPK / pSTAT5 / STAT5 pFLT3 / FLT3 / pERK / ERK / pS6 / S6 pKIT / KIT 24227820
Growth inhibition assay Cell viability 24623852
In Vivo
In vivo

Crenolanib, a PDGFR inhibitor, suppresses lung cancer cell proliferation and inhibits tumor growth in vivo
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00949624 Completed
Advanced Solid Tumors
Arog Pharmaceuticals Inc.
 December 2005 Phase 1

Chemical Information & Solubility

Molecular Weight 443.54 Formula

C26H29N5O2
CAS No. 670220-88-9 SDF Download Crenolanib SDF
Smiles CC1(COC1)COC2=CC3=C(C=C2)N(C=N3)C4=NC5=C(C=CC=C5N6CCC(CC6)N)C=C4
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 88 mg/mL ( (198.4 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 88 mg/mL

Water : Insoluble


Molecular Weight Calculator

In vivo
Batch:

Add solvents to the product individually and in order.


In vivo Formulation Calculator

Preparing Stock Solutions

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.
Tags: buy Crenolanib | Crenolanib supplier | purchase Crenolanib | Crenolanib cost | Crenolanib manufacturer | order Crenolanib | Crenolanib distributor