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Details

Stereochemistry ACHIRAL
Molecular Formula C26H29N5O2.C6H6O3S
Molecular Weight 601.716
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CRENOLANIB BESYLATE

SMILES

OS(=O)(=O)C1=CC=CC=C1.CC7(COC2=CC=C3N(C=NC3=C2)C4=CC=C5C=CC=C(N6CCC(N)CC6)C5=N4)COC7

InChI

InChIKey=ARQUTWAXTHJROR-UHFFFAOYSA-N
InChI=1S/C26H29N5O2.C6H6O3S/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;7-10(8,9)6-4-2-1-3-5-6/h2-8,13,17,19H,9-12,14-16,27H2,1H3;1-5H,(H,7,8,9)

HIDE SMILES / InChI

Molecular Formula C26H29N5O2
Molecular Weight 443.5408
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C6H6O3S
Molecular Weight 158.175
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/24227820

Crenolanib is an orally active, highly selective, small molecule, next generation inhibitor of platelet-derived growth factor receptor (PDGFR) tyrosine kinase. Crenolanib, manufactured by Arog Pharmaceuticals in Dallas, is taken orally with chemotherapy. The compound is currently being evaluated for safety and efficacy in clinical trials for various types of cancer, including acute myeloid leukemia (AML), gastrointestinal stromal tumor (GIST), and glioma. Crenolanib is an orally bioavailable, selective small molecule inhibitor of type III tyrosine kinases with nanomolar potencies against platelet-derived growth factor receptors (PDGFR) (isoforms PDGFRα and PDGFRβ) and Fms-related tyrosine kinase 3 (FLT3). Besides PDGFR and FLT3, crenolanib does not inhibit any other known receptor tyrosine kinase (RTK) (e.g. VEGFR and FGFR) or any other serine/threonine kinase (e.g., Abl, Raf) at clinically achievable concentrations. Preclinical trials have shown Crenolanib to be active in inhibiting both wild-type and mutant FLT3. Crenolanib is cytotoxic to the FLT3/ITD-expressing leukemia cell lines Molm14 and MV411, with IC50s of 7 nM and 8 nM, respectively. In immunoblots, crenolanib inhibited phosphorylation of both the wild-type FLT3 receptor (in SEMK2 cells) and the FLT3/ITD receptor (in Molm14 cells) in culture medium with IC50s of 1-3 nM. Importantly, the IC50 of crenolanib against the D835Y mutated form of FLT3 was 8.8 nM in culture medium. Furthermore, crenolanib had cytotoxic activity against primary samples that were obtained from patients who had developed D835 mutations while receiving FLT3 TKIs. In vitro, the IC50 of crenolanib for inhibition of FLT3/ITD in plasma was found to be 34 nM, indicating a relatively low degree of plasma protein binding. From pharmacokinetic studies of crenolanib in solid tumor patients, steady state trough plasma levels of roughly 500 nM were found to be safe and tolerable, suggesting that crenolanib could potentially inhibit the target in vivo. Crenolanib has no significant activity against c-KIT, which may be an advantage in that myelosuppression can be avoided.1Furthermore, there was no evidence of QTc prolongation in patients treated with crenolanib. In summary, crenolanib offers a number of advantages over other FLT3 TKIs. Clinical trials of crenolanib in AML patients with FLT3 activating mutations are being planned.

Originator

Curator's Comment: # Pfizer

Approval Year

TargetsConditions

Conditions

Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumors.
2012 Aug 15
Patents

Sample Use Guides

single-agent crenolanib at 100 mg PO TID
Route of Administration: Oral
In Vitro Use Guide
Crenolanib is cytotoxic to the FLT3/ITD-expressing leukemia cell lines Molm14 and MV411, with IC50s of 7 nM and 8 nM, respectively.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:29:47 GMT 2023
Edited
by admin
on Fri Dec 15 15:29:47 GMT 2023
Record UNII
MC4B01024K
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CRENOLANIB BESYLATE
USAN  
USAN  
Official Name English
Crenolanib besilate [WHO-DD]
Common Name English
4-PIPERIDINAMINE, 1-(2-(5-((3-METHYL-3-OXETANYL)METHOXY)-1H-BENZIMIDAZOL-1-YL)-8-QUINOLINYL)-, BENZENESULFONATE (1:1)
Systematic Name English
CP-868,596-26
Code English
CP-868596-26
Code English
ARO-002-26
Code English
CRENOLANIB BESYLATE [USAN]
Common Name English
CRENOLANIB BESILATE
WHO-DD  
Common Name English
596-26
Code English
Classification Tree Code System Code
FDA ORPHAN DRUG 320910
Created by admin on Fri Dec 15 15:29:47 GMT 2023 , Edited by admin on Fri Dec 15 15:29:47 GMT 2023
EU-Orphan Drug EU/3/16/1748
Created by admin on Fri Dec 15 15:29:47 GMT 2023 , Edited by admin on Fri Dec 15 15:29:47 GMT 2023
NCI_THESAURUS C1967
Created by admin on Fri Dec 15 15:29:47 GMT 2023 , Edited by admin on Fri Dec 15 15:29:47 GMT 2023
Code System Code Type Description
PUBCHEM
18435899
Created by admin on Fri Dec 15 15:29:47 GMT 2023 , Edited by admin on Fri Dec 15 15:29:47 GMT 2023
PRIMARY
CAS
670220-93-6
Created by admin on Fri Dec 15 15:29:47 GMT 2023 , Edited by admin on Fri Dec 15 15:29:47 GMT 2023
PRIMARY
FDA UNII
MC4B01024K
Created by admin on Fri Dec 15 15:29:47 GMT 2023 , Edited by admin on Fri Dec 15 15:29:47 GMT 2023
PRIMARY
NCI_THESAURUS
C106204
Created by admin on Fri Dec 15 15:29:47 GMT 2023 , Edited by admin on Fri Dec 15 15:29:47 GMT 2023
PRIMARY
ChEMBL
CHEMBL2105728
Created by admin on Fri Dec 15 15:29:47 GMT 2023 , Edited by admin on Fri Dec 15 15:29:47 GMT 2023
PRIMARY
USAN
XX-155
Created by admin on Fri Dec 15 15:29:47 GMT 2023 , Edited by admin on Fri Dec 15 15:29:47 GMT 2023
PRIMARY
SMS_ID
100000177181
Created by admin on Fri Dec 15 15:29:47 GMT 2023 , Edited by admin on Fri Dec 15 15:29:47 GMT 2023
PRIMARY
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