U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C26H29N5O2
Molecular Weight 443.5408
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CRENOLANIB

SMILES

CC6(COC1=CC2=C(C=C1)N(C=N2)C3=NC4=C(C=CC=C4N5CCC(N)CC5)C=C3)COC6

InChI

InChIKey=DYNHJHQFHQTFTP-UHFFFAOYSA-N
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

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

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
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 Thu Jul 06 03:14:07 UTC 2023
Edited
by admin
on Thu Jul 06 03:14:07 UTC 2023
Record UNII
LQF7I567TQ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CRENOLANIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
CP-868,596
Code English
CRENOLANIB [USAN]
Common Name English
CP-868
Code English
ARO-002
Code English
ARO 002
Code English
CP-868596
Code English
1-(2-{5-[(3-Methyloxetan-3-yl)methoxy]-1H-benzimidazol-1-yl}quinolin-8-yl)piperidin-4-amine
Systematic Name English
Crenolanib [WHO-DD]
Common Name English
4-PIPERIDINAMINE, 1-(2-(5-((3-METHYL-3-OXETANYL)METHOXY)-1H-BENZIMIDAZOL-1-YL)-8-QUINOLINYL)-
Systematic Name English
CP 868596
Code English
crenolanib [INN]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 706819
Created by admin on Thu Jul 06 03:14:07 UTC 2023 , Edited by admin on Thu Jul 06 03:14:07 UTC 2023
NCI_THESAURUS C1967
Created by admin on Thu Jul 06 03:14:07 UTC 2023 , Edited by admin on Thu Jul 06 03:14:07 UTC 2023
FDA ORPHAN DRUG 363812
Created by admin on Thu Jul 06 03:14:07 UTC 2023 , Edited by admin on Thu Jul 06 03:14:07 UTC 2023
FDA ORPHAN DRUG 335911
Created by admin on Thu Jul 06 03:14:07 UTC 2023 , Edited by admin on Thu Jul 06 03:14:07 UTC 2023
Code System Code Type Description
DRUG BANK
DB11832
Created by admin on Thu Jul 06 03:14:07 UTC 2023 , Edited by admin on Thu Jul 06 03:14:07 UTC 2023
PRIMARY
USAN
XX-154
Created by admin on Thu Jul 06 03:14:07 UTC 2023 , Edited by admin on Thu Jul 06 03:14:07 UTC 2023
PRIMARY
WIKIPEDIA
CRENOLANIB
Created by admin on Thu Jul 06 03:14:07 UTC 2023 , Edited by admin on Thu Jul 06 03:14:07 UTC 2023
PRIMARY
NCI_THESAURUS
C64639
Created by admin on Thu Jul 06 03:14:07 UTC 2023 , Edited by admin on Thu Jul 06 03:14:07 UTC 2023
PRIMARY
SMS_ID
100000170917
Created by admin on Thu Jul 06 03:14:07 UTC 2023 , Edited by admin on Thu Jul 06 03:14:07 UTC 2023
PRIMARY
FDA UNII
LQF7I567TQ
Created by admin on Thu Jul 06 03:14:07 UTC 2023 , Edited by admin on Thu Jul 06 03:14:07 UTC 2023
PRIMARY
CHEBI
145365
Created by admin on Thu Jul 06 03:14:07 UTC 2023 , Edited by admin on Thu Jul 06 03:14:07 UTC 2023
PRIMARY
EPA CompTox
DTXSID50985873
Created by admin on Thu Jul 06 03:14:07 UTC 2023 , Edited by admin on Thu Jul 06 03:14:07 UTC 2023
PRIMARY
ChEMBL
CHEMBL2105728
Created by admin on Thu Jul 06 03:14:07 UTC 2023 , Edited by admin on Thu Jul 06 03:14:07 UTC 2023
PRIMARY
INN
9459
Created by admin on Thu Jul 06 03:14:07 UTC 2023 , Edited by admin on Thu Jul 06 03:14:07 UTC 2023
PRIMARY
CAS
670220-88-9
Created by admin on Thu Jul 06 03:14:07 UTC 2023 , Edited by admin on Thu Jul 06 03:14:07 UTC 2023
PRIMARY
PUBCHEM
10366136
Created by admin on Thu Jul 06 03:14:07 UTC 2023 , Edited by admin on Thu Jul 06 03:14:07 UTC 2023
PRIMARY
EVMPD
SUB185102
Created by admin on Thu Jul 06 03:14:07 UTC 2023 , Edited by admin on Thu Jul 06 03:14:07 UTC 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
INHIBITOR
Related Record Type Details
ACTIVE MOIETY