BGT-226 MALEATE

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C28H25F3N6O2.C4H4O4
Molecular Weight	650.6045
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C/C(O)=O.COC1=CC=C(C=N1)C2=CC=C3N=CC4=C(N(C(=O)N4C)C5=CC=C(N6CCNCC6)C(=C5)C(F)(F)F)C3=C2

InChI

InChIKey=YUXMAKUNSXIEKN-BTJKTKAUSA-N

InChI=1S/C28H25F3N6O2.C4H4O4/c1-35-24-16-33-22-6-3-17(18-4-8-25(39-2)34-15-18)13-20(22)26(24)37(27(35)38)19-5-7-23(21(14-19)28(29,30)31)36-11-9-32-10-12-36;5-3(6)1-2-4(7)8/h3-8,13-16,32H,9-12H2,1-2H3;1-2H,(H,5,6)(H,7,8)/b;2-1-

HIDE SMILES / InChI

Molecular Formula	C4H4O4
Molecular Weight	116.0722
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Molecular Formula	C28H25F3N6O2
Molecular Weight	534.5323
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26003166
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/22357447 | https://www.ncbi.nlm.nih.gov/pubmed/21959532

BGT 226 is an orally available, small molecule, the dual inhibitor of mammalian target of rapamycin (mTOR) and phosphatidylinositol 3'kinase (PI3K), developed by Novartis for the treatment of solid tumors, including advanced breast cancer. A phase I/II trial was completed in the US, Canada, and Spain, and a phase I trial was completed in Japan. However, development appears to have been discontinued.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
PI3-kinase class I 8 Target ID: CHEMBL3559703 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21959532	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Breast cancer 434 Sources: https://clinicaltrials.gov/ct2/show/NCT00600275	Primary	Phase II 1132	Unknown Approved Use Unknown
Cowden syndrome 2 Sources: https://clinicaltrials.gov/ct2/show/NCT00600275	Primary	Phase II 1132	Unknown Approved Use Unknown
Cancer 592 Sources: https://clinicaltrials.gov/ct2/show/NCT00742105	Primary	Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
2.45 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22357447	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	BGT-226 MALEATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5.21 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22357447	125 mg single, oral dose: 125 mg route of administration: Oral experiment type: SINGLE co-administered:	BGT-226 MALEATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22357447	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:	BGT-226 MALEATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
26.97 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22357447	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	BGT-226 MALEATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
78.75 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22357447	125 mg single, oral dose: 125 mg route of administration: Oral experiment type: SINGLE co-administered:	BGT-226 MALEATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
32.86 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22357447	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:	BGT-226 MALEATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
8.61 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22357447	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	BGT-226 MALEATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8.62 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22357447	125 mg single, oral dose: 125 mg route of administration: Oral experiment type: SINGLE co-administered:	BGT-226 MALEATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7.61 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22357447	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:	BGT-226 MALEATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461

Drug as perpetrator

Target	Modality	Activity
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=377020374	inconclusive [IC50 21.3174 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=377020374	no
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=174006504	yes [IC50 0.0083 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=377020374	yes [IC50 1.5092 uM]

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY116338	https://www.001chemical.com/chem/search?q=DY116338
001 Chemical	DY116339	https://www.001chemical.com/chem/search?q=DY116339
1PlusChem LLC	1P009CUL	https://www.1pchem.com/search?query=1P009CUL
AChemBlock	10292	http://www.achemblock.com/catalogsearch/result/?q=10292
AK Scientific	2605AH	https://aksci.com/item_detail.php?cat=2605AH
AK Scientific	SYN1178	https://aksci.com/item_detail.php?cat=SYN1178A
AK Scientific	SYN1178A	https://aksci.com/item_detail.php?cat=SYN1178A
Angene	AGN-PC-0BS0H7	http://www.angenechemical.com/productshow/AGN-PC-0BS0H7.html
ApexBio Technology	A8488	https://www.apexbt.com/catalogsearch/result/?q=A8488
AstaTech	41080	http://astatechinc.com/CPSResult.php?CRNO=41080
Axon MedChem	2029	https://www.axonmedchem.com/product/2029
BLD Pharm	BD305526	http://www.bldpharm.com/search/Search.html?keyword=BD305526
BLD Pharm	BD445648	http://www.bldpharm.com/search/Search.html?keyword=BD445648
BOC Sciences	1245537-68-1	http://www.bocsci.com/description.asp?cas=1245537-68-1
Chem Scene	CS-0583	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0583
ChemShuttle	104926	https://www.chemshuttle.com/catalogsearch/result/?q=104926
ChemShuttle	140472	https://www.chemshuttle.com/catalogsearch/result/?q=140472
Combi-Blocks	QJ-7099	http://www.combi-blocks.com/cgi-bin/find.cgi?QJ-7099
Debye Scientific	DA-18144	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-18144
KeyOrganics	AS-16312	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16312
KeyOrganics	AS-16313	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16313
Lab Seeker	SC-86995	http://www.labseeker.com/search.php?keywords=SC-86995&category=0
LabSeeker	SC-86995	http://www.labseeker.com/search.php?keywords=SC-86995&category=0
Matrix Scientific	145265	http://www.matrixscientific.com/145265.html
MedChem Express	HY-13334	https://www.medchemexpress.com/search.html?q=HY-13334&ft=&fa=&fp=
MolPort	MolPort-023-219-185	https://www.molport.com/shop/molecule-link/MolPort-023-219-185
MolPort	MolPort-038-941-942	https://www.molport.com/shop/molecule-link/MolPort-038-941-942
Molcore	MC116338	http://www.molcore.com/CatMC116338.html
Molcore	MC116339	http://www.molcore.com/CatMC116339.html
Molnova	M10992	https://www.molnova.com/en/serch-list.html?keywords=M10992
MuseChem	I000973	https://www.musechem.com/product/I000973.html
MuseChem	I004206	https://www.musechem.com/product/I004206.html
Ryan Scientific	101-94017	https://ryansci.com/products?q=101-94017&list_q=&search_type=exact
ShangHai Biochempartner	BCP000502	http://www.biochempartner.com/search_BCP000502
ShangHai Biochempartner	BCP03599	http://www.biochempartner.com/search_BCP03599
Synthonix	13261	https://synthonix.com/catalogsearch/result/?q=13261
TargetMol	T6072	https://www.targetmol.com/search?keyword=T6072
eMolecules	300625314	https://orderbb.emolecules.com/search/#?query=300625314
eMolecules	43366922	https://orderbb.emolecules.com/search/#?query=43366922
eMolecules	44848382	https://orderbb.emolecules.com/search/#?query=44848382
eMolecules	50406347	https://orderbb.emolecules.com/search/#?query=50406347
eMolecules	56973921	https://orderbb.emolecules.com/search/#?query=56973921
eNovation Chemicals	D552003	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D552003&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-3505483344	https://mcule.com/MCULE-3505483344/
mcule	MCULE-4152502074	https://mcule.com/MCULE-4152502074/
mcule	MCULE-7009092951	https://mcule.com/MCULE-7009092951/

PubMed

Title	Date	PubMed
		252160667
Preclinical modeling of combined phosphatidylinositol-3-kinase inhibition with endocrine therapy for estrogen receptor-positive breast cancer.	2011 Mar 1	21362200

Patents

Sample Use Guides

In Vivo Use Guide

Patients were received BGT226 (2.5, 5, 10, 20, 40, 80, and 125 mg) as a single oral daily dose, three times weekly (TIW) (every other day), 2 h after a light breakfast, and to continue fasting for two more hours. Treatment was continued on 28-day treatment cycles until unacceptable toxicity, disease progression, or consent withdrawal.

Route of Administration: Oral

In Vitro Use Guide

HCC, Mahlavu, SNU475, SNU449, HepG2 and Hep3B cells were incubated in the presence of increasing concentrations of the BGT 226 for either 24 or 48 h. Cell viability rates were then analyzed by MTT assays. After 48 h of treatment cell viability impairment was evident, with an IC50 value ranging from 0.55 mkM for Mahlavu to 1.35 mkM for HepG2 cells

Substance Class	Chemical Created by `admin` on `Sat Dec 16 05:14:32 GMT 2023` Edited by `admin` on `Sat Dec 16 05:14:32 GMT 2023`
Record UNII	4YG62LG876
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BGT-226 MALEATE

Common Name

English

2H-IMIDAZO(4,5-C)QUINOLIN-2-ONE, 1,3-DIHYDRO-8-(6-METHOXY-3-PYRIDINYL)-3-METHYL-1-(4-(1-PIPERAZINYL)-3-(TRIFLUOROMETHYL)PHENYL)-, (2Z)-2-BUTENEDIOATE (1:1)

Systematic Name

English

BGT226

Code

English

BGT-226

Common Name

English

NVP-BGT-226

Code

English

NVP-BGT226

Code

English

Code System Code Type Description

FDA UNII

4YG62LG876