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Details

Stereochemistry ACHIRAL
Molecular Formula C27H28ClFN6O.2C7H8O3S
Molecular Weight 851.405
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AV-412

SMILES

CC1=CC=C(C=C1)S(O)(=O)=O.CC2=CC=C(C=C2)S(O)(=O)=O.CN3CCN(CC3)C(C)(C)C#CC4=CC5=NC=NC(NC6=CC(Cl)=C(F)C=C6)=C5C=C4NC(=O)C=C

InChI

InChIKey=GTWJVFFZCKODEV-UHFFFAOYSA-N
InChI=1S/C27H28ClFN6O.2C7H8O3S/c1-5-25(36)33-23-16-20-24(30-17-31-26(20)32-19-6-7-22(29)21(28)15-19)14-18(23)8-9-27(2,3)35-12-10-34(4)11-13-35;2*1-6-2-4-7(5-3-6)11(8,9)10/h5-7,14-17H,1,10-13H2,2-4H3,(H,33,36)(H,30,31,32);2*2-5H,1H3,(H,8,9,10)

HIDE SMILES / InChI

Molecular Formula C7H8O3S
Molecular Weight 172.202
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C27H28ClFN6O
Molecular Weight 507.002
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

MP-412 (AV-412) is a potent dual inhibitor of EGFR and ErbB2 tyrosine kinases, including the mutant EGFR (L858R,T790M), which is clinically resistant to the EGFR-specific kinase inhibitors erlotinib and gefitinib. AV-412 has potential as a therapeutic agent for the treatment of cancers expressing EGFR and ErbB2, especially those resistant to the first generation of small-molecule inhibitors.AVEO Pharmaceuticals was developing AV-412 for the treatment of cancer, however development has been discontinued.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
19.0 nM [IC50]
1.4 nM [IC50]
41.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
500 mg multiple, oral
Highest studied dose
Dose: 500 mg
Route: oral
Route: multiple
Dose: 500 mg
Sources:
unhealthy, ADULT
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
DLT: Acute renal failure, Diarrhea...
Dose limiting toxicities:
Acute renal failure (grade 3)
Diarrhea (grade 3)
Sources:
100 mg 3 times / day multiple, oral
MTD
Dose: 100 mg, 3 times / day
Route: oral
Route: multiple
Dose: 100 mg, 3 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
400 mg 1 times / week multiple, oral
MTD
Dose: 400 mg, 1 times / week
Route: oral
Route: multiple
Dose: 400 mg, 1 times / week
Sources:
unhealthy, ADULT
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
200 mg 3 times / week multiple, oral
Studied dose
Dose: 200 mg, 3 times / week
Route: oral
Route: multiple
Dose: 200 mg, 3 times / week
Sources:
unhealthy, ADULT
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
DLT: Diarrhea, Vomiting...
Dose limiting toxicities:
Diarrhea (grade 3)
Vomiting (grade 3)
Nausea (grade 3)
Sources:
AEs

AEs

AESignificanceDosePopulation
Acute renal failure grade 3
DLT
500 mg multiple, oral
Highest studied dose
Dose: 500 mg
Route: oral
Route: multiple
Dose: 500 mg
Sources:
unhealthy, ADULT
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Diarrhea grade 3
DLT
500 mg multiple, oral
Highest studied dose
Dose: 500 mg
Route: oral
Route: multiple
Dose: 500 mg
Sources:
unhealthy, ADULT
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Diarrhea grade 3
DLT
200 mg 3 times / week multiple, oral
Studied dose
Dose: 200 mg, 3 times / week
Route: oral
Route: multiple
Dose: 200 mg, 3 times / week
Sources:
unhealthy, ADULT
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Nausea grade 3
DLT
200 mg 3 times / week multiple, oral
Studied dose
Dose: 200 mg, 3 times / week
Route: oral
Route: multiple
Dose: 200 mg, 3 times / week
Sources:
unhealthy, ADULT
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Vomiting grade 3
DLT
200 mg 3 times / week multiple, oral
Studied dose
Dose: 200 mg, 3 times / week
Route: oral
Route: multiple
Dose: 200 mg, 3 times / week
Sources:
unhealthy, ADULT
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [IC50 16.3601 uM]
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Antitumor activity of a dual epidermal growth factor receptor and ErbB2 kinase inhibitor MP-412 (AV-412) in mouse xenograft models.
2009 Aug
Ubiquitination and downregulation of ErbB2 and estrogen receptor-alpha by kinase inhibitor MP-412 in human breast cancer cells.
2011 Sep
Patents

Sample Use Guides

Unknown
Route of Administration: Oral
AV-412 (MP-412) consistently inhibited the growth of all cell lines, with IC50 of 0.3, 0.5, and 1.4 µM in H1781, H1975, and H1650 cells respectively.
Substance Class Chemical
Created
by admin
on Fri Dec 15 17:02:17 GMT 2023
Edited
by admin
on Fri Dec 15 17:02:17 GMT 2023
Record UNII
Z541VW0W40
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AV-412
Common Name English
MP-412 DITOSYLATE
Code English
MP 412 [WHO-DD]
Common Name English
2-PROPENAMIDE, N-(4-((3-CHLORO-4-FLUOROPHENYL)AMINO)-7-(3-METHYL-3-(4-METHYL-1-PIPERAZINYL)-1-BUTYN-1-YL)-6-QUINAZOLINYL)-, 4-METHYLBENZENESULFONATE (1:2)
Common Name English
MP-412
Common Name English
Code System Code Type Description
NCI_THESAURUS
C64627
Created by admin on Fri Dec 15 17:02:17 GMT 2023 , Edited by admin on Fri Dec 15 17:02:17 GMT 2023
PRIMARY
CAS
451493-31-5
Created by admin on Fri Dec 15 17:02:17 GMT 2023 , Edited by admin on Fri Dec 15 17:02:17 GMT 2023
PRIMARY
FDA UNII
Z541VW0W40
Created by admin on Fri Dec 15 17:02:17 GMT 2023 , Edited by admin on Fri Dec 15 17:02:17 GMT 2023
PRIMARY
DRUG BANK
DB06021
Created by admin on Fri Dec 15 17:02:17 GMT 2023 , Edited by admin on Fri Dec 15 17:02:17 GMT 2023
PRIMARY
PUBCHEM
11700696
Created by admin on Fri Dec 15 17:02:17 GMT 2023 , Edited by admin on Fri Dec 15 17:02:17 GMT 2023
PRIMARY
ChEMBL
CHEMBL3545002
Created by admin on Fri Dec 15 17:02:17 GMT 2023 , Edited by admin on Fri Dec 15 17:02:17 GMT 2023
PRIMARY
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ACTIVE MOIETY