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Details

Stereochemistry ABSOLUTE
Molecular Formula C30H31F3N8O
Molecular Weight 576.6153
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BAFETINIB

SMILES

CN(C)[C@H]1CCN(CC2=CC=C(C=C2C(F)(F)F)C(=O)NC3=CC(NC4=NC(=CC=N4)C5=CN=CN=C5)=C(C)C=C3)C1

InChI

InChIKey=ZGBAJMQHJDFTQJ-DEOSSOPVSA-N
InChI=1S/C30H31F3N8O/c1-19-4-7-23(13-27(19)39-29-36-10-8-26(38-29)22-14-34-18-35-15-22)37-28(42)20-5-6-21(25(12-20)30(31,32)33)16-41-11-9-24(17-41)40(2)3/h4-8,10,12-15,18,24H,9,11,16-17H2,1-3H3,(H,37,42)(H,36,38,39)/t24-/m0/s1

HIDE SMILES / InChI

Molecular Formula C30H31F3N8O
Molecular Weight 576.6153
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Bafetinib (NS-187, INNO-406) is a second-generation tyrosine kinase inhibitor in development by CytRx under license from Nippon Shinyaku for treating Bcr-Abl+ leukemia's, including chronic myelogenous leukemia (CML) and Philadelphia+ acute lymphoblastic leukemia. It is a rationally developed tyrosine kinase inhibitor based on the chemical structure of imatinib, with modifications added to improve binding and potency against Bcr-Abl kinase. Besides Abl, bafetinib targets the Src family kinase Lyn, which has been associated with resistance to imatinib in CML. In preclinical studies, bafetinib was 25- to 55-fold more potent than imatinib in vitro and ≥ 10-fold more potent in vivo. Bafetinibinhibits 12 of the 13 most frequent imatinib-resistant Bcr-Abl point mutations, but not a Thr315Ile mutation. A small fraction of bafetinib crosses the blood-brain barrier, reaching brain concentrations adequate for suppression of Bcr-Abl+ cells. Data from a phase I clinical trial conducted in patients with imatinib-resistant or -intolerant CML have confirmed that bafetinib has clinical activity in this setting, inducing a major cytogenetic response in 19% of those patients in chronic phase. Currently, bafetinib is being developed in two phase II clinical trials for patients with B-cell chronic lymphocytic leukemia and prostate cancer, and a trial is in progress for patients with brain tumors. In 2005, the compound was licensed to Innovive Pharmaceuticals (acquired by CytRx Oncology in 2008) by Nippon Shinyaku on a worldwide basis, with the exception of Japan, for the treatment of CML. Orphan drug designation was assigned to the compound for the treatment of CML in the U.S in 2007 and in the E.U. in 2010. Bafetinib is in phase II for the treatment of hormone-refractory prostate cancer and chronic lymphocytic leukemia.

CNS Activity

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
Patents

Patents

Sample Use Guides

In Vivo Use Guide
250 mg orally twice daily
Route of Administration: Oral
In Vitro Use Guide
Bafetinib blocks WT Bcr-Abl autophosphorylation and its downstream kinase activity with IC50 of 11 nM and 22 nM in K562 and 293T cells, respectively.
Substance Class Chemical
Created
by admin
on Mon Oct 21 20:46:54 UTC 2019
Edited
by admin
on Mon Oct 21 20:46:54 UTC 2019
Record UNII
NVW4Z03I9B
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BAFETINIB
INN   MART.   USAN   WHO-DD  
USAN   INN  
Official Name English
N-(3-((4,5'-BIPYRIMIDIN)-2-YLAMINO)-4-METHYLPHENYL)-4-(((3S)-3-(DIMETHYLAMINO)PYRROLIDIN-1-YL)METHYL)-3-(TRIFLUOROMETHYL)BENZAMIDE
Systematic Name English
BAFETINIB [MART.]
Common Name English
NS-187
Code English
BAFETINIB [WHO-DD]
Common Name English
N-(3-(4',5'-BIPYRIMIDIN-2-YLAMINO)-4-METHYLPHENYL)-4-(((3S)-3-(DIMETHYLAMINO)PYRROLIDIN-1-YL)METHYL)-3-(TRIFLUOROMETHYL)BENZAMIDE
Systematic Name English
BAFETINIB [USAN]
Common Name English
INNO-406
Code English
BENZAMIDE, N-(3-((4,5'-BIPYRIMIDIN)-2-YLAMINO)-4-METHYLPHENYL)-4-(((3S)-3-(DIMETHYLAMINO)-1-PYRROLIDINYL)METHYL)-3-(TRIFLUOROMETHYL)-
Systematic Name English
CNS-9
Code English
BAFETINIB [INN]
Common Name English
Classification Tree Code System Code
EU-Orphan Drug EU/3/10/731
Created by admin on Mon Oct 21 20:46:54 UTC 2019 , Edited by admin on Mon Oct 21 20:46:54 UTC 2019
NCI_THESAURUS C1967
Created by admin on Mon Oct 21 20:46:54 UTC 2019 , Edited by admin on Mon Oct 21 20:46:54 UTC 2019
FDA ORPHAN DRUG 233206
Created by admin on Mon Oct 21 20:46:54 UTC 2019 , Edited by admin on Mon Oct 21 20:46:54 UTC 2019
NCI_THESAURUS C129825
Created by admin on Mon Oct 21 20:46:54 UTC 2019 , Edited by admin on Mon Oct 21 20:46:54 UTC 2019
Code System Code Type Description
WIKIPEDIA
Bafetinib
Created by admin on Mon Oct 21 20:46:54 UTC 2019 , Edited by admin on Mon Oct 21 20:46:54 UTC 2019
PRIMARY
INN
8984
Created by admin on Mon Oct 21 20:46:54 UTC 2019 , Edited by admin on Mon Oct 21 20:46:54 UTC 2019
PRIMARY
ChEMBL
CHEMBL206834
Created by admin on Mon Oct 21 20:46:54 UTC 2019 , Edited by admin on Mon Oct 21 20:46:54 UTC 2019
PRIMARY
EVMPD
SUB96036
Created by admin on Mon Oct 21 20:46:54 UTC 2019 , Edited by admin on Mon Oct 21 20:46:54 UTC 2019
PRIMARY
CAS
859212-16-1
Created by admin on Mon Oct 21 20:46:54 UTC 2019 , Edited by admin on Mon Oct 21 20:46:54 UTC 2019
PRIMARY
PUBCHEM
11387605
Created by admin on Mon Oct 21 20:46:54 UTC 2019 , Edited by admin on Mon Oct 21 20:46:54 UTC 2019
PRIMARY
NCI_THESAURUS
C62516
Created by admin on Mon Oct 21 20:46:54 UTC 2019 , Edited by admin on Mon Oct 21 20:46:54 UTC 2019
PRIMARY
Related Record Type Details
TRANSPORTER -> INHIBITOR
TARGET -> INHIBITOR
TRANSPORTER -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY