GSK-1059615

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H11N3O2S
Molecular Weight	333.364
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O=C1NC(=O)\C(S1)=C\C2=CC=C3N=CC=C(C4=CC=NC=C4)C3=C2

InChI

InChIKey=QDITZBLZQQZVEE-YBEGLDIGSA-N

InChI=1S/C18H11N3O2S/c22-17-16(24-18(23)21-17)10-11-1-2-15-14(9-11)13(5-8-20-15)12-3-6-19-7-4-12/h1-10H,(H,21,22,23)/b16-10-

HIDE SMILES / InChI

Molecular Formula	C18H11N3O2S
Molecular Weight	333.364
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19713247 | https://www.ncbi.nlm.nih.gov/pubmed/28881606

GSK 1059615, a pyridinylquinoline derivative, is a novel PI3K kinase and mTOR dual inhibitor. GSK1059615 was in phase I clinical trial in patients with solid tumors or lymphoma, but this study was terminated prematurely due to lack of sufficient exposure following single- and repeat dosing. In addition, recently was shown, that GSK 1059615 in xenograft mice models possessed anti-head and neck squamous cell carcinoma (HNSCC) cell activity.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 9 Target ID: P42336 Gene ID: 5290.0 Gene Symbol: PIK3CA Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/19589091	Inhibitor 8297	0.4 nM [IC50]
Serine/threonine-protein kinase mTOR 35 Target ID: P42345 Gene ID: 2475.0 Gene Symbol: MTOR Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/28881606	Inhibitor 8297
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform 4 Target ID: P42338 Gene ID: 5291.0 Gene Symbol: PIK3CB Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/19589091	Inhibitor 8297	0.6 nM [IC50]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform 5 Target ID: P48736 Gene ID: 5294.0 Gene Symbol: PIK3CG Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/19589091	Inhibitor 8297	5.0 nM [IC50]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform 9 Target ID: O00329 Gene ID: 5293.0 Gene Symbol: PIK3CD Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/19589091	Inhibitor 8297	2.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Lymphoma 58 Sources: https://clinicaltrials.gov/ct2/show/NCT00695448	Primary		Phase I 428	Unknown Approved Use Unknown
Head and neck squamous cell carcinoma 32 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28881606	Primary		Preclinical	Unknown Approved Use Unknown

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=377020465	yes [IC50 3.6626 uM]

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P005XEQ	https://www.1pchem.com/search?query=1P005XEQ
AChemBlock	P50916	http://www.achemblock.com/catalogsearch/result/?q=P50916
AK Scientific	X7431	https://aksci.com/item_detail.php?cat=X7431
Angene	AGN-PC-0WHA03	http://www.angenechemical.com/productshow/AGN-PC-0WHA03.html
AstaTech	C16828	http://astatechinc.com/CPSResult.php?CRNO=C16828
BLD Pharm	BD328431	http://www.bldpharm.com/search/Search.html?keyword=BD328431
Cayman Chemical	11569	http://www.caymanchem.com/app/template/Product.vm/catalog/11569
Chem Scene	CS-0187	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0187
ChemShuttle	134393	https://www.chemshuttle.com/catalogsearch/result/?q=134393
Excenen	EX-A2223	http://www.excenen.com/searchresultlist.php?id=EX-A2223
Lab Network	LN01315691	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01315691
Matrix Scientific	153976	http://www.matrixscientific.com/153976.html
MedChem Express	HY-12036	https://www.medchemexpress.com/search.html?q=HY-12036&ft=&fa=&fp=
MolPort	MolPort-023-277-040	https://www.molport.com/shop/molecule-link/MolPort-023-277-040
Molnova	M16846	https://www.molnova.com/en/serch-list.html?keywords=M16846
MuseChem	I005685	https://www.musechem.com/product/I005685.html
MuseChem	R057568	https://www.musechem.com/product/R057568.html
ShangHai Biochempartner	BCP02498	http://www.biochempartner.com/search_BCP02498
TargetMol	T2357	https://www.targetmol.com/search?keyword=T2357
Tocris	4026	https://www.tocris.com/search.php?Type=QuickSearch&Value=4026
Wonderchem	WD0741S	http://www.wonder-chem.com/search.html?text=WD0741S
eMolecules	32176567	https://orderbb.emolecules.com/search/#?query=32176567
eMolecules	44842009	https://orderbb.emolecules.com/search/#?query=44842009
eMolecules	45922940	https://orderbb.emolecules.com/search/#?query=45922940
eMolecules	85163617	https://orderbb.emolecules.com/search/#?query=85163617
mcule	MCULE-8016634550	https://mcule.com/MCULE-8016634550/
mcule	MCULE-8832290272	https://mcule.com/MCULE-8832290272/
mcule	MCULE-9088353533	https://mcule.com/MCULE-9088353533/

PubMed

Title	Date	PubMed
Discovery of GSK2126458, a Highly Potent Inhibitor of PI3K and the Mammalian Target of Rapamycin.	2010 Apr 8	24900173
Identification of druggable targets for radiation mitigation using a small interfering RNA screening assay.	2012 Sep	22747550

Sample Use Guides

In Vivo Use Guide

GSK1059615 is dosed orally once daily for 21 days of a 28-day cycle. Patients continue treatment for subsequent cycles as long as eligible and receiving benefit.

Route of Administration: Oral

In Vitro Use Guide

GSK1059615 is a potent PI3K-mTOR duel inhibitor, was tested PI3K-AKT-mTOR signaling in GSK1059615-treated cells. The treatment with GSK1059615 (3 μM) in SCC-9 cells and “OCC1” primary cancer cells dramatically inhibited phosphorylation of PI3K p85 (Tyr-458), AKT (Ser-473), mTOR (Ser-2448) and S6K1 (Thr-389). Thus, GSK1059615 apparently blocked PI3K-AKT-mTOR signaling cascade activation in head and neck squamous (HNSCC) cells. Remarkably, the basal activation of PI3K-AKT-mTOR cascade was quite low in the oral epithelial cells (“Oepi1”). p-PI3K p85, p-AKT, p-mTOR and p-S6K1 were almost undetected in the epithelial cells. These might explain why these epithelial cells were not killed by. Interestingly, ERK activation, tested by p-ERK1/2 (Thr-202/Tyr-204), was not altered by the same GSK1059615 (3 μM) treatment. Thus, GSK1059615 blocks PI3K-AKT-mTOR activation in HNSCC cells.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 06:51:57 GMT 2023` Edited by `admin` on `Sat Dec 16 06:51:57 GMT 2023`
Record UNII	07YMO87363
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

GSK-1059615

Common Name

English

GSK1059615

Code

English

2,4-THIAZOLIDINEDIONE, 5-((4-(4-PYRIDINYL)-6-QUINOLINYL)METHYLENE)-, (5Z)-

Systematic Name

English

GSK-615

Code

English

GSK615

Code

English

Code System Code Type Description

CAS

958852-01-2