BMS-690514

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H24N6O2
Molecular Weight	368.4329
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC(NC2=NC=NN3C=CC(CN4CC[C@@H](N)[C@H](O)C4)=C23)=CC=C1

InChI

InChIKey=CSGQVNMSRKWUSH-IAGOWNOFSA-N

InChI=1S/C19H24N6O2/c1-27-15-4-2-3-14(9-15)23-19-18-13(5-8-25(18)22-12-21-19)10-24-7-6-16(20)17(26)11-24/h2-5,8-9,12,16-17,26H,6-7,10-11,20H2,1H3,(H,21,22,23)/t16-,17-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C19H24N6O2
Molecular Weight	368.4329
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20166197
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800025400 https://www.ncbi.nlm.nih.gov/pubmed/23490650

BMS-690514 is a potent, reversible oral inhibitor of epidermal growth factor receptor (EGFR/HER-1), HER-2 and -4, and vascular endothelial growth factor receptors (VEGFRs)-1 to -3 offering targeted inhibition of tumour growth and vascularisation in a single agent. Bristol-Myers Squibb was developing BMS 690514, as an oral treatment for cancer. BMS-690514 had being in phase II for the treatment of breast cancer; non-small cell lung cancer, but later these studies were discontinued.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
PC-9 3 Target ID: CHEMBL614102 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23490650 \| https://www.ncbi.nlm.nih.gov/pubmed/21531814	Inhibitor 8297	9.0 nM [IC50]
Receptor protein-tyrosine kinase erbB-4 12 Target ID: CHEMBL3009 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21531814	Inhibitor 8297	60.0 nM [IC50]
Receptor protein-tyrosine kinase erbB-2 35 Target ID: CHEMBL1824 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21531814	Inhibitor 8297	19.0 nM [IC50]
Vascular endothelial growth factor receptor 1 41 Target ID: CHEMBL1868 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21531814	Inhibitor 8297	50.0 nM [IC50]
Vascular endothelial growth factor receptor 2 104 Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21531814	Inhibitor 8297	50.0 nM [IC50]
Vascular endothelial growth factor receptor 3 41 Target ID: CHEMBL1955 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21531814 \| http://clincancerres.aacrjournals.org/content/clincanres/suppl/2011/06/17/1078-0432.CCR-10-3417.DC1/T3.FL1-6.pdf	Inhibitor 8297	25.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Non small cell lung cancer 7 Sources: https://clinicaltrials.gov/ct2/show/NCT00743938	Primary		Phase II 1132	Unknown Approved Use Unknown
Breast cancer 434 Sources: https://clinicaltrials.gov/ct2/show/NCT01068704	Primary		Phase II 1132	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781 substrate 1737	inhibitor 1767 substrate 1037	inhibitor 1852 substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 1478 CYP2C8 911 CYP1A2 1524 P-gp 1461 CYP2B6 810 CYP3A4/5 278 CYP2A6 707	UGT1A1 418 UGT 192 CYP2C19 991 CYP1A2 1054 UGT1A10 291 UGT2B4/7 1 UGT2B15 203 CYP2E1 667 P-gp 1537 UGT2B17 213 UGT1A3 422 CYP3A5 395 UGT1A4 347 CYP1B1 92 UGT1A6 307 CYP2A6 543 UGT1A7 236 CYP2B6 664 UGT1A8 283 UGT1A9 380 CYP2C8 693	CYP2B6 547 CYP1A2 701 UGT1A1 69 CYP1A1 108

Drug as perpetrator

Target	Modality	Activity
P-gp 1650	inhibitor 3277	likely [Inhibition 10 uM]
CYP2B6 1001	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	likely
CYP3A4 1925	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	likely
UGT1A1 254	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	no
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20166197/	weak [IC50 >40 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20166197/ \| https://pubmed.ncbi.nlm.nih.gov/21673131/	weak [IC50 >40 uM]
CYP2C8 965	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20166197/	weak [IC50 >40 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20166197/ \| https://pubmed.ncbi.nlm.nih.gov/21673131/	weak [IC50 >40 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20166197/	weak [IC50 >40 uM]
CYP3A4/5 335	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20166197/ \| https://pubmed.ncbi.nlm.nih.gov/21673131/	weak [IC50 >40 uM]
CYP2A6 739	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	weak [IC50 >45 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	weak [IC50 >45 uM]
CYP1A1 218	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	yes
CYP1A2 1692	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20668249/ \| https://pubmed.ncbi.nlm.nih.gov/20166197/	major [Km ~1 uM]	no (pharmacogenomic study) Comment: No clinically relevant differences between poor and extensive metabolizers Sources: https://pubmed.ncbi.nlm.nih.gov/20668249/ \| https://pubmed.ncbi.nlm.nih.gov/20166197/
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20668249/ \| https://pubmed.ncbi.nlm.nih.gov/20166197/ \| https://pubmed.ncbi.nlm.nih.gov/23436267/	major [Km ~23 uM]	yes (co-administration study) Comment: Ketoconazole increased dose-normalized Cmax and AUCinf by 55% and 127%. Sources: https://pubmed.ncbi.nlm.nih.gov/20668249/ \| https://pubmed.ncbi.nlm.nih.gov/20166197/ \| https://pubmed.ncbi.nlm.nih.gov/23436267/
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	major
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20166197/	no
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20166197/	no
UGT1A1 418	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	no
UGT1A10 291	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	no
UGT1A3 422	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	no
UGT1A4 347	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	no
UGT1A6 307	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	no
UGT1A7 236	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	no
UGT1A8 283	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	no
UGT1A9 380	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	no
UGT2B15 203	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	no
UGT2B17 213	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	no
CYP1B1 92	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	unlikely
CYP2A6 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	unlikely
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	unlikely
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	unlikely
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	unlikely
CYP3A5 395	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	unlikely
UGT1A1 418	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20668249/	unlikely
UGT 192	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20668249/ \| https://pubmed.ncbi.nlm.nih.gov/20166197/	yes
UGT2B4/7 1	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21673131/	yes
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20166197/ \| https://pubmed.ncbi.nlm.nih.gov/23436267/	yes	yes (co-administration study) Comment: Ketoconazole increased dose-normalized Cmax and AUCinf by 55% and 127%. Sources: https://pubmed.ncbi.nlm.nih.gov/20166197/ \| https://pubmed.ncbi.nlm.nih.gov/23436267/

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY100111	https://www.001chemical.com/chem/search?q=DY100111
1PlusChem LLC	1P00GUIN	https://www.1pchem.com/search?query=1P00GUIN
AChemBlock	C-2973	http://www.achemblock.com/catalogsearch/result/?q=C-2973
AK Scientific	0913AF	https://aksci.com/item_detail.php?cat=0913AF
AstaTech	C13451	http://astatechinc.com/CPSResult.php?CRNO=C13451
AstaTech	P12423	http://astatechinc.com/CPSResult.php?CRNO=P12423
BLD Pharm	BD301507	http://www.bldpharm.com/search/Search.html?keyword=BD301507
BOC Sciences	859853-30-8	http://www.bocsci.com/description.asp?cas=859853-30-8
BioSynth	J-501257	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/J-501257
Chem Scene	CS-M1183	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-M1183
ChemShuttle	101178	https://www.chemshuttle.com/catalogsearch/result/?q=101178
Combi-Blocks	QM-7559	http://www.combi-blocks.com/cgi-bin/find.cgi?QM-7559
Fluorochem	502781	http://www.fluorochem.co.uk/Products/Product?code=502781
KeyOrganics	CS-15397	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=CS-15397
Lab Network	LN00169691	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00169691
Matrix Scientific	69274	http://www.matrixscientific.com/069274.html
MedChem Express	HY-10333	https://www.medchemexpress.com/search.html?q=HY-10333&ft=&fa=&fp=
MolPort	MolPort-020-393-325	https://www.molport.com/shop/molecule-link/MolPort-020-393-325
MolPort	MolPort-046-593-158	https://www.molport.com/shop/molecule-link/MolPort-046-593-158
Molcore	MC100111	http://www.molcore.com/CatMC100111.html
Molnova	M16232	https://www.molnova.com/en/serch-list.html?keywords=M16232
ShangHai Biochempartner	BCP000362	http://www.biochempartner.com/search_BCP000362
Synthonix	SL100047	http://www.synthon-lab.com/search.php?cas_or_id=SL100047&cas_id_field=1
Synthonix	1197	https://synthonix.com/catalogsearch/result/?q=1197
Synthonix	A65740	https://synthonix.com/catalogsearch/result/?q=A65740
Tetrahedron	TS86847	http://www.thsci.com/search.do?q=TS86847
eMolecules	275181491	https://orderbb.emolecules.com/search/#?query=275181491
eMolecules	300607242	https://orderbb.emolecules.com/search/#?query=300607242
eMolecules	36553283	https://orderbb.emolecules.com/search/#?query=36553283
eMolecules	50285824	https://orderbb.emolecules.com/search/#?query=50285824
eNovation Chemicals	D500114	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D500114&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-1050657001	https://mcule.com/MCULE-1050657001/
mcule	MCULE-6012766942	https://mcule.com/MCULE-6012766942/
mcule	MCULE-8033837307	https://mcule.com/MCULE-8033837307/

PubMed

Title	Date	PubMed
A novel epidermal growth factor receptor inhibitor promotes apoptosis in non-small cell lung cancer cells resistant to erlotinib.	2007 Jul 1	17616683
Preclinical pharmacokinetics and in vitro metabolism of BMS-690514, a potent inhibitor of EGFR and VEGFR2.	2010 Aug	20166197
Mechanistic studies on a P450-mediated rearrangement of BMS-690514: conversion of a pyrrolotriazine to a hydroxypyridotriazine.	2011 Jan 14	21080678

Patents

Sample Use Guides

In Vivo Use Guide

Tablets, Oral, 200 mg, once daily,

Route of Administration: Oral

In Vitro Use Guide

Non–small cell lung tumor cells with exon 19 deletion (HCC4006, HCC827, and PC9) were highly sensitive to BMS-690514, which inhibits their proliferation with IC50 values of 2 to 35 nmol/L. Breast and gastric tumor cell lines that have HER2 gene amplification (N87, SNU-216, AU565, BT474, KPL4, and HCC202) were inhibited with IC50 values of 20 to 60 nmol/L

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:53:46 UTC 2023` Edited by `admin` on `Fri Dec 15 15:53:46 UTC 2023`
Record UNII	VKU5X213Q7
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

BMS-690514

Common Name

English

3-PIPERIDINOL, 4-AMINO-1-((4-((3-METHOXYPHENYL)AMINO)PYRROLO(2,1-F)(1,2,4)TRIAZIN-5-YL)METHYL)-, (3R,4R)-

Systematic Name

English

BMS 690514

Common Name

English

BMS 690514 [WHO-DD]

Common Name

English

BMS 6690514

Common Name

English

(3R,4R)-4-AMINO-1-((4-((3-METHOXYPHENYL)AMINO)PYRROLO(2,1-F)(1,2,4)TRIAZIN-5-YL)METHYL)-3-PIPERIDINOL

Systematic Name

English

Code System Code Type Description

PUBCHEM

11349170