GSK-1070916

Details

Stereochemistry	ACHIRAL
Molecular Formula	C30H33N7O
Molecular Weight	507.6293
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCN1C=C(C(=N1)C2=CC=C(NC(=O)N(C)C)C=C2)C3=C4C=C(NC4=NC=C3)C5=CC=CC(CN(C)C)=C5

InChI

InChIKey=QTBWCSQGBMPECM-UHFFFAOYSA-N

InChI=1S/C30H33N7O/c1-6-37-19-26(28(34-37)21-10-12-23(13-11-21)32-30(38)36(4)5)24-14-15-31-29-25(24)17-27(33-29)22-9-7-8-20(16-22)18-35(2)3/h7-17,19H,6,18H2,1-5H3,(H,31,33)(H,32,38)

HIDE SMILES / InChI

Molecular Formula	C30H33N7O
Molecular Weight	507.6293
Charge	0
Count

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

Description
Sources: http://adisinsight.springer.com/drugs/800032133
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/19284385 | https://www.ncbi.nlm.nih.gov/pubmed/20420387 | https://www.ncbi.nlm.nih.gov/pubmed/19567821

GSK1070916 is a novel, azaindole derived, reversible and ATP-competitive inhibitor of the Aurora B/C kinases. GSK1070916 inhibits the proliferation of tumor cells and has antitumor effects in 10 human tumor xenograft models including breast, colon, lung, and two leukemia models. Nemucore Medical Innovations and Cancer Research UK are developing NMI 900 (previously GSK 1070916) for the intravenous treatment of cancer. The product was originally developed by GlaxoSmithKline. A phase I/II trial in patients with solid tumours has been completed in the UK. Phase II development in ovarian cancer is underway in the US.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serine/threonine-protein kinase Aurora-C 10 Target ID: CHEMBL3935 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19284385 \| https://www.ncbi.nlm.nih.gov/pubmed/20420387	Inhibitor 8504		1.5 nM [Ki]
Serine/threonine-protein kinase Aurora-B 28 Target ID: CHEMBL2185 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19284385 \| https://www.ncbi.nlm.nih.gov/pubmed/20420387	Inhibitor 8504		0.38 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Solid tumors 147 Sources: http://adisinsight.springer.com/drugs/800032133	Primary		Phase I 438	Unknown Approved Use Unknown
Ovarian cancer 160 Sources: http://adisinsight.springer.com/drugs/800032133	Primary		Phase II 1147	Unknown Approved Use Unknown

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.98 h EXPERIMENT https://ascopubs.org/doi/abs/10.1200/jco.2013.31.15_suppl.2525	85 mg/m² single, intravenous dose: 85 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		GSK-1070916A plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
102.2 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 102.2 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 102.2 mg/m2, 1 times / day Sources: https://ascopubs.org/doi/abs/10.1200/jco.2013.31.15_suppl.2525	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: unknown Food Status: UNKNOWN Sources: https://ascopubs.org/doi/abs/10.1200/jco.2013.31.15_suppl.2525	DLT: Febrile neutropenia... Other AEs: neutropenia... Dose limiting toxicities: Febrile neutropenia (1 pt) Other AEs: neutropenia (grade 4, 2 patients) Sources: https://ascopubs.org/doi/abs/10.1200/jco.2013.31.15_suppl.2525
85 mg/m2 1 times / day multiple, intravenous MTD Dose: 85 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 85 mg/m2, 1 times / day Sources: https://ascopubs.org/doi/abs/10.1200/jco.2013.31.15_suppl.2525	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: unknown Food Status: UNKNOWN Sources: https://ascopubs.org/doi/abs/10.1200/jco.2013.31.15_suppl.2525	Disc. AE: neutropenia... AEs leading to discontinuation/dose reduction: neutropenia (grade 4, 5 patients) Sources: https://ascopubs.org/doi/abs/10.1200/jco.2013.31.15_suppl.2525

AEs

AE	Significance	Dose	Population
Febrile neutropenia	1 pt DLT	102.2 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 102.2 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 102.2 mg/m2, 1 times / day Sources: https://ascopubs.org/doi/abs/10.1200/jco.2013.31.15_suppl.2525	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: unknown Food Status: UNKNOWN Sources: https://ascopubs.org/doi/abs/10.1200/jco.2013.31.15_suppl.2525
neutropenia	grade 4, 2 patients	102.2 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 102.2 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 102.2 mg/m2, 1 times / day Sources: https://ascopubs.org/doi/abs/10.1200/jco.2013.31.15_suppl.2525	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: unknown Food Status: UNKNOWN Sources: https://ascopubs.org/doi/abs/10.1200/jco.2013.31.15_suppl.2525
neutropenia	grade 4, 5 patients Disc. AE	85 mg/m2 1 times / day multiple, intravenous MTD Dose: 85 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 85 mg/m2, 1 times / day Sources: https://ascopubs.org/doi/abs/10.1200/jco.2013.31.15_suppl.2525	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: unknown Food Status: UNKNOWN Sources: https://ascopubs.org/doi/abs/10.1200/jco.2013.31.15_suppl.2525

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
activator 150 inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 P-gp 1741 CYP2C19 2057	P-gp 2052 BCRP 697

Drug as perpetrator

Target	Modality	Activity
P-gp 1932	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363677496	inconclusive [IC50 6.3209 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20420387/	moderate [IC50 38 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20420387/	weak [IC50 81 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20420387/	weak [IC50 >33 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20420387/	yes [IC50 12 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20420387/	yes [IC50 15 uM]
CYP3A4 2633	activator 342 Sources: https://pubmed.ncbi.nlm.nih.gov/20420387/	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
BCRP 697	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/33450491/	yes
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/33519482/	yes

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P019GAJ	https://www.1pchem.com/search?query=1P019GAJ
AChemBlock	M22593	http://www.achemblock.com/catalogsearch/result/?q=M22593
AK Scientific	SYN5723	https://aksci.com/item_detail.php?cat=SYN5723
AOBIOUS INC	AOB87380	http://aobious.com/aobious/search?search_query=AOB87380
ApexBio Technology	A4127	https://www.apexbt.com/catalogsearch/result/?q=A4127
AstaTech	F17366	http://astatechinc.com/CPSResult.php?CRNO=F17366
BLD Pharm	BD165440	http://www.bldpharm.com/search/Search.html?keyword=BD165440
Chem Scene	CS-0008	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0008
ChemShuttle	134938	https://www.chemshuttle.com/catalogsearch/result/?q=134938
Debye Scientific	DB-079843	https://www.debyesci.com/index.php?id=product&ext[cno]=DB-079843
eMolecules	36723765	https://orderbb.emolecules.com/search/#?query=36723765
eNovation Chemicals	D320005	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D320005&searchbtn.x=0&searchbtn.y=0
Excenen	EX-A021	http://www.excenen.com/searchresultlist.php?id=EX-A021
KeyOrganics	AS-17024	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-17024
mcule	MCULE-9657732360	https://mcule.com/MCULE-9657732360/
MedChem Express	HY-70044	https://www.medchemexpress.com/search.html?q=HY-70044&ft=&fa=&fp=
Molnova	M16749	https://www.molnova.com/en/serch-list.html?keywords=M16749
MolPort	MolPort-009-682-973	https://www.molport.com/shop/molecule-link/MolPort-009-682-973
MuseChem	I005606	https://www.musechem.com/product/I005606.html
Selleck Chemicals	S2740	http://www.selleckchem.com/search.html?searchDTO.searchParam=S2740
ShangHai Biochempartner	BCP02610	http://www.biochempartner.com/search_BCP02610
Synthonix	SL101155	http://www.synthon-lab.com/search.php?cas_or_id=SL101155&cas_id_field=1
Toronto Research Chemicals	G797455	https://www.trc-canada.com/product-detail/?CatNum=G797455

PubMed

Title	Date	PubMed
Phthalazinone pyrazoles as potent, selective, and orally bioavailable inhibitors of Aurora-A kinase.	2011-01-13	21128645
Discovery of GSK1070916, a potent and selective inhibitor of Aurora B/C kinase.	2010-05-27	20420387
GSK1070916, a potent Aurora B/C kinase inhibitor with broad antitumor activity in tissue culture cells and human tumor xenograft models.	2009-07	19567821
Biochemical characterization of GSK1070916, a potent and selective inhibitor of Aurora B and Aurora C kinases with an extremely long residence time1.	2009-05-13	19284385
Validating Aurora B as an anti-cancer drug target.	2006-09-01	16912073
Aurora-kinase inhibitors as anticancer agents.	2004-12	15573114
Mitotic mechanics: the auroras come into view.	2003-12	14644191

Patents

Sample Use Guides

In Vivo Use Guide

Nemucore Medical Innovations and Cancer Research UK are developing NMI 900 (previously GSK 1070916A), a selective Aurora kinase B/C inhibitor, for the intravenous treatment of cancer, however, dosage of the drug is not disclosed. GSK1070916 was evaluated for its ability to inhibit the growth of various tumor xenografts in nude mice. Repeated i.p. administration at 25, 50, or 100 mg/kg once daily (5 consecutive days with 2 days off for up to three cycles) produced antitumor activity in all models evaluated with regressions (complete or partial).

Route of Administration: Other

In Vitro Use Guide

GSK1070916 inhibits the proliferation of tumor cells with EC(50) values of <10 nmol/L in over 100 cell lines spanning a broad range of tumor types.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 23:30:44 GMT 2025` Edited by `admin` on `Mon Mar 31 23:30:44 GMT 2025`
Record UNII	8VLB51V7HO
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

GSK-1070916

Code

English

GSK 1070916A

Preferred Name

English

UREA, N'-(4-(4-(2-(3-((DIMETHYLAMINO)METHYL)PHENYL)-1H-PYRROLO(2,3-B)PYRIDIN-4-YL)-1-ETHYL-1H-PYRAZOL-3-YL)PHENYL)-N,N-DIMETHYL-

Systematic Name

English

GSK1070916

Code

English

3-(4-(4-(2-(3-((DIMETHYLAMINO)METHYL)PHENYL)-1H-PYRROLO(2,3-B)PYRIDIN-4-YL)-1-ETHYL-1H-PYRAZOL-3-YL)PHENYL)-1,1-DIMETHYLUREA

Systematic Name

English

GSK-1070916A

Code

English

GSK1070916A

Code

English

Code System Code Type Description

EPA CompTox

DTXSID70241403