AV-412

Investigational

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 Search

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17888033 | http://adisinsight.springer.com/drugs/800022373 | http://adisinsight.springer.com/drugs/800022373

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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Receptor protein-tyrosine kinase erbB-2 35 Target ID: CHEMBL1824 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17888033	Inhibitor 8297	19.0 nM [IC50]
Epidermal growth factor receptor erbB1 58 Target ID: CHEMBL203 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17888033	Inhibitor 8297	1.4 nM [IC50]
Tyrosine-protein kinase ABL 29 Target ID: CHEMBL1862 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17888033	Inhibitor 8297	41.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 592 Sources: http://adisinsight.springer.com/drugs/800022373	Primary		Phase I 428	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
500 mg multiple, oral Highest studied dose Dose: 500 mg Route: oral Route: multiple Dose: 500 mg Sources: https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.3103	unhealthy, ADULT Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.3103	DLT: Acute renal failure, Diarrhea... Dose limiting toxicities: Acute renal failure (grade 3) Diarrhea (grade 3) Sources: https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.3103
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: https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.3103	unhealthy, ADULT Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.3103	Sources: https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.3103
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: https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.3103	unhealthy, ADULT Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.3103	Sources: https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.3103
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: https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.3103	unhealthy, ADULT Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.3103	DLT: Diarrhea, Vomiting... Dose limiting toxicities: Diarrhea (grade 3) Vomiting (grade 3) Nausea (grade 3) Sources: https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.3103

AEs

AE	Significance	Dose	Population
Acute renal failure	grade 3 DLT	500 mg multiple, oral Highest studied dose Dose: 500 mg Route: oral Route: multiple Dose: 500 mg Sources: https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.3103	unhealthy, ADULT Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.3103
Diarrhea	grade 3 DLT	500 mg multiple, oral Highest studied dose Dose: 500 mg Route: oral Route: multiple Dose: 500 mg Sources: https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.3103	unhealthy, ADULT Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.3103
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: https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.3103	unhealthy, ADULT Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.3103
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: https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.3103	unhealthy, ADULT Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.3103
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: https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.3103	unhealthy, ADULT Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.3103

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=377020296	yes [IC50 16.3601 uM]

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY107054	https://www.001chemical.com/chem/search?q=DY107054
1PlusChem LLC	1P00DBLK	https://www.1pchem.com/search?query=1P00DBLK
1PlusChem LLC	1P00DBLL	https://www.1pchem.com/search?query=1P00DBLL
AChemBlock	M15313	http://www.achemblock.com/catalogsearch/result/?q=M15313
AChemBlock	M15314	http://www.achemblock.com/catalogsearch/result/?q=M15314
AK Scientific	3191AH	https://aksci.com/item_detail.php?cat=3191AH
AK Scientific	3459AH	https://aksci.com/item_detail.php?cat=3459AH
AK Scientific	SYN1012	https://aksci.com/item_detail.php?cat=SYN1012
Ambeed	A116496	http://www.ambeed.com/search/Search.html?keyword=A116496
Angene	AGN-PC-0RTE3G	http://www.angenechemical.com/productshow/AGN-PC-0RTE3G.html
AstaTech	42348	http://astatechinc.com/CPSResult.php?CRNO=42348
AstaTech	42351	http://astatechinc.com/CPSResult.php?CRNO=42351
BLD Pharm	BD316935	http://www.bldpharm.com/search/Search.html?keyword=BD316935
BLD Pharm	BD448265	http://www.bldpharm.com/search/Search.html?keyword=BD448265
BOC Sciences	451492-95-8	http://www.bocsci.com/description.asp?cas=451492-95-8
Chem Scene	CS-2401	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-2401
Chem Scene	CS-2402	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-2402
ChemShuttle	112409	https://www.chemshuttle.com/catalogsearch/result/?q=112409
ChemShuttle	169508	https://www.chemshuttle.com/catalogsearch/result/?q=169508
Combi-Blocks	QV-3093	http://www.combi-blocks.com/cgi-bin/find.cgi?QV-3093
Combi-Blocks	QV-4312	http://www.combi-blocks.com/cgi-bin/find.cgi?QV-4312
Excenen	EX-A755	http://www.excenen.com/searchresultlist.php?id=EX-A755
Excenen	EX-A756	http://www.excenen.com/searchresultlist.php?id=EX-A756
KeyOrganics	AS-16187	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16187
Matrix Scientific	132611	http://www.matrixscientific.com/132611.html
MedChem Express	HY-10346	https://www.medchemexpress.com/search.html?q=HY-10346A&ft=&fa=&fp=
MedChem Express	HY-10346A	https://www.medchemexpress.com/search.html?q=HY-10346A&ft=&fa=&fp=
MolPort	MolPort-021-804-922	https://www.molport.com/shop/molecule-link/MolPort-021-804-922
MolPort	MolPort-039-139-483	https://www.molport.com/shop/molecule-link/MolPort-039-139-483
Molcore	MC107054	http://www.molcore.com/CatMC107054.html
MuseChem	I003290	https://www.musechem.com/product/I003290.html
ShangHai Biochempartner	BCP01955	http://www.biochempartner.com/search_BCP01955
ShangHai Biochempartner	BCP23783	http://www.biochempartner.com/search_BCP23783
Toronto Research Chemicals	A794725	https://www.trc-canada.com/product-detail/?CatNum=A794725
Toronto Research Chemicals	K570513	https://www.trc-canada.com/product-detail/?CatNum=K570513
eMolecules	31507569	https://orderbb.emolecules.com/search/#?query=31507569
eMolecules	37153249	https://orderbb.emolecules.com/search/#?query=37153249
mcule	MCULE-6507730788	https://mcule.com/MCULE-6507730788/
mcule	MCULE-7356052600	https://mcule.com/MCULE-7356052600/

PubMed

Title	Date	PubMed
Pharmacological characterization of MP-412 (AV-412), a dual epidermal growth factor receptor and ErbB2 tyrosine kinase inhibitor.	2007 Dec	17888033
Antitumor activity of a dual epidermal growth factor receptor and ErbB2 kinase inhibitor MP-412 (AV-412) in mouse xenograft models.	2009 Aug	19459856
Ubiquitination and downregulation of ErbB2 and estrogen receptor-alpha by kinase inhibitor MP-412 in human breast cancer cells.	2011 Sep	21503962

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Oral

In Vitro Use Guide

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.

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