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Details

Stereochemistry ABSOLUTE
Molecular Formula C30H31F3N8O
Molecular Weight 576.6165
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BAFETINIB

SMILES

Cc1ccc(cc1Nc2nccc(-c3cncnc3)n2)N=C(c4ccc(CN5CC[C@@]([H])(C5)N(C)C)c(c4)C(F)(F)F)O

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 576.6165
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/20310049 http://www.med-chemist.com/2010/06/bafetinib-demonstrates-significant.html

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

Curator's Comment:: Bafetinib crosses the blood-brain barrier, reaching brain concentrations adequate for suppression of Bcr-Abl+ cells. Bafetinib is capable of preventing the progression of dopaminergic neuronal damage in a toxin-induced C57 mouse model of PD.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
26.0 nM [IC50]
19.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
164 ng/mL
360 mg 2 times / day multiple, oral
dose: 360 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BAFETINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
129 ng/mL
360 mg 2 times / day single, oral
dose: 360 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BAFETINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
661 ng/mL
30 mg/kg single, oral
dose: 30 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
BAFETINIB plasma
Mus musculus
population: UNKNOWN
age: ADULT
sex: FEMALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1000 ng × h/mL
360 mg 2 times / day multiple, oral
dose: 360 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BAFETINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
522 ng × h/mL
360 mg 2 times / day single, oral
dose: 360 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BAFETINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2294 ng × h/mL
30 mg/kg single, oral
dose: 30 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
BAFETINIB plasma
Mus musculus
population: UNKNOWN
age: ADULT
sex: FEMALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1 h
30 mg/kg single, oral
dose: 30 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
BAFETINIB plasma
Mus musculus
population: UNKNOWN
age: ADULT
sex: FEMALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
480 mg 2 times / day multiple, oral
Highest studied dose
Dose: 480 mg, 2 times / day
Route: oral
Route: multiple
Dose: 480 mg, 2 times / day
Sources:
unhealthy
n = 5
Health Status: unhealthy
Condition: chronic myeloid leukemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources:
DLT: transaminase elevation, thrombocytopenia...
Dose limiting toxicities:
transaminase elevation
thrombocytopenia
Sources:
240 mg 2 times / day multiple, oral (unknown)
RP2D
Dose: 240 mg, 2 times / day
Route: oral
Route: multiple
Dose: 240 mg, 2 times / day
Sources:
unhealthy
n = 17
Health Status: unhealthy
Condition: CML - chronic Myelogenous Leukemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 17
Sources:
Other AEs: ALT elevation, AST elevation...
Other AEs:
ALT elevation (grade 3, 1 pt)
AST elevation (grade 2, 1 pt)
transaminase elevation
Sources:
AEs

AEs

AESignificanceDosePopulation
thrombocytopenia DLT
480 mg 2 times / day multiple, oral
Highest studied dose
Dose: 480 mg, 2 times / day
Route: oral
Route: multiple
Dose: 480 mg, 2 times / day
Sources:
unhealthy
n = 5
Health Status: unhealthy
Condition: chronic myeloid leukemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources:
transaminase elevation DLT
480 mg 2 times / day multiple, oral
Highest studied dose
Dose: 480 mg, 2 times / day
Route: oral
Route: multiple
Dose: 480 mg, 2 times / day
Sources:
unhealthy
n = 5
Health Status: unhealthy
Condition: chronic myeloid leukemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources:
transaminase elevation
240 mg 2 times / day multiple, oral (unknown)
RP2D
Dose: 240 mg, 2 times / day
Route: oral
Route: multiple
Dose: 240 mg, 2 times / day
Sources:
unhealthy
n = 17
Health Status: unhealthy
Condition: CML - chronic Myelogenous Leukemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 17
Sources:
AST elevation grade 2, 1 pt
240 mg 2 times / day multiple, oral (unknown)
RP2D
Dose: 240 mg, 2 times / day
Route: oral
Route: multiple
Dose: 240 mg, 2 times / day
Sources:
unhealthy
n = 17
Health Status: unhealthy
Condition: CML - chronic Myelogenous Leukemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 17
Sources:
ALT elevation grade 3, 1 pt
240 mg 2 times / day multiple, oral (unknown)
RP2D
Dose: 240 mg, 2 times / day
Route: oral
Route: multiple
Dose: 240 mg, 2 times / day
Sources:
unhealthy
n = 17
Health Status: unhealthy
Condition: CML - chronic Myelogenous Leukemia
Sex: M+F
Food Status: UNKNOWN
Population Size: 17
Sources:
PubMed

PubMed

TitleDatePubMed
INNO-406, a novel BCR-ABL/Lyn dual tyrosine kinase inhibitor, suppresses the growth of Ph+ leukemia cells in the central nervous system, and cyclosporine A augments its in vivo activity.
2007 Jan 1
Neuroprotective efficacy of a new brain-penetrating C-Abl inhibitor in a murine Parkinson's disease model.
2013
Bafetinib (INNO-406) reverses multidrug resistance by inhibiting the efflux function of ABCB1 and ABCG2 transporters.
2016 May 9
Patents

Patents

Sample Use Guides

250 mg orally twice daily
Route of Administration: Oral
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 Fri Jun 25 22:52:40 UTC 2021
Edited
by admin
on Fri Jun 25 22:52:40 UTC 2021
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 Fri Jun 25 22:52:40 UTC 2021 , Edited by admin on Fri Jun 25 22:52:40 UTC 2021
NCI_THESAURUS C1967
Created by admin on Fri Jun 25 22:52:40 UTC 2021 , Edited by admin on Fri Jun 25 22:52:40 UTC 2021
FDA ORPHAN DRUG 233206
Created by admin on Fri Jun 25 22:52:40 UTC 2021 , Edited by admin on Fri Jun 25 22:52:40 UTC 2021
NCI_THESAURUS C129825
Created by admin on Fri Jun 25 22:52:40 UTC 2021 , Edited by admin on Fri Jun 25 22:52:40 UTC 2021
Code System Code Type Description
WIKIPEDIA
Bafetinib
Created by admin on Fri Jun 25 22:52:40 UTC 2021 , Edited by admin on Fri Jun 25 22:52:40 UTC 2021
PRIMARY
INN
8984
Created by admin on Fri Jun 25 22:52:40 UTC 2021 , Edited by admin on Fri Jun 25 22:52:40 UTC 2021
PRIMARY
DRUG BANK
DB11851
Created by admin on Fri Jun 25 22:52:40 UTC 2021 , Edited by admin on Fri Jun 25 22:52:40 UTC 2021
PRIMARY
ChEMBL
CHEMBL206834
Created by admin on Fri Jun 25 22:52:40 UTC 2021 , Edited by admin on Fri Jun 25 22:52:40 UTC 2021
PRIMARY
FDA UNII
NVW4Z03I9B
Created by admin on Fri Jun 25 22:52:40 UTC 2021 , Edited by admin on Fri Jun 25 22:52:40 UTC 2021
PRIMARY
EVMPD
SUB96036
Created by admin on Fri Jun 25 22:52:40 UTC 2021 , Edited by admin on Fri Jun 25 22:52:40 UTC 2021
PRIMARY
CAS
859212-16-1
Created by admin on Fri Jun 25 22:52:40 UTC 2021 , Edited by admin on Fri Jun 25 22:52:40 UTC 2021
PRIMARY
PUBCHEM
11387605
Created by admin on Fri Jun 25 22:52:40 UTC 2021 , Edited by admin on Fri Jun 25 22:52:40 UTC 2021
PRIMARY
NCI_THESAURUS
C62516
Created by admin on Fri Jun 25 22:52:40 UTC 2021 , Edited by admin on Fri Jun 25 22:52:40 UTC 2021
PRIMARY
Related Record Type Details
TRANSPORTER -> INHIBITOR
TARGET -> INHIBITOR
TRANSPORTER -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY