LY-2090314

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C28H25FN6O3
Molecular Weight	512.5349
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC1=CC2=C3N(CCN(C2)C(=O)N4CCCCC4)C=C(C3=C1)C5=C(C(=O)NC5=O)C6=CN=C7C=CC=CN67

InChI

InChIKey=HRJWTAWVFDCTGO-UHFFFAOYSA-N

InChI=1S/C28H25FN6O3/c29-18-12-17-15-34(28(38)32-7-3-1-4-8-32)11-10-33-16-20(19(13-18)25(17)33)23-24(27(37)31-26(23)36)21-14-30-22-6-2-5-9-35(21)22/h2,5-6,9,12-14,16H,1,3-4,7-8,10-11,15H2,(H,31,36,37)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23305709
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/26735141 | https://www.ncbi.nlm.nih.gov/pubmed/26403509 | https://clinicaltrials.gov/ct2/show/NCT01632306

LY-2090314 is a GSK-3alpha and GSK-3beta inhibitor developed by Eli Lilly. Phase 2 clinical trials of LY-2090314 as a signle agenst against acute leukemia did not show clinical benefit. LY-2090314 was studied in combination pemetrexed and carboplatin against solid tumors, and in combination with FOLFOX, gemcitabine, and nab-paclitaxel against pancreatic cancer.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glycogen synthase kinase-3 alpha 5 Target ID: CHEMBL2850 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23305709	Inhibitor 8297		1.5 nM [IC50]
Glycogen synthase kinase-3 beta 51 Target ID: CHEMBL262 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23305709	Inhibitor 8297		0.9 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Acute leukemia 31 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26735141	Primary	Phase II 1132	Unknown Approved Use Unknown
Advanced solid cancer 28 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26403509	Primary	Phase I 428	Unknown Approved Use Unknown
Pancreatic cancer 97 Sources: https://clinicaltrials.gov/ct2/show/NCT01632306	Primary	Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
1700 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23305709	120 mg single, intravenous dose: 120 mg route of administration: Intravenous experiment type: SINGLE co-administered: PEMETREXED\|carboplatin	PEMETREXED\|carboplatin	LY-2090314 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
603 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23305709	40 mg 1 times / day single, intravenous dose: 40 mg route of administration: Intravenous experiment type: SINGLE co-administered: PEMETREXED\|carboplatin	PEMETREXED\|carboplatin	LY-2090314 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
3310 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23305709	120 mg single, intravenous dose: 120 mg route of administration: Intravenous experiment type: SINGLE co-administered: PEMETREXED\|carboplatin	PEMETREXED\|carboplatin	LY-2090314 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
976 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23305709	40 mg 1 times / day single, intravenous dose: 40 mg route of administration: Intravenous experiment type: SINGLE co-administered: PEMETREXED\|carboplatin	PEMETREXED\|carboplatin	LY-2090314 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.97 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23305709	120 mg single, intravenous dose: 120 mg route of administration: Intravenous experiment type: SINGLE co-administered: PEMETREXED\|carboplatin	PEMETREXED\|carboplatin	LY-2090314 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.15 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23305709	40 mg 1 times / day single, intravenous dose: 40 mg route of administration: Intravenous experiment type: SINGLE co-administered: PEMETREXED\|carboplatin	PEMETREXED\|carboplatin	LY-2090314 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23305709	40 mg 1 times / day single, intravenous dose: 40 mg route of administration: Intravenous experiment type: SINGLE co-administered: PEMETREXED\|carboplatin	PEMETREXED\|carboplatin	LY-2090314 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00ECUN	https://www.1pchem.com/search?query=1P00ECUN
ApexBio Technology	A3570	https://www.apexbt.com/catalogsearch/result/?q=A3570
AstaTech	41538	http://astatechinc.com/CPSResult.php?CRNO=41538
BLD Pharm	BD630787	http://www.bldpharm.com/search/Search.html?keyword=BD630787
Chem Scene	CS-1633	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1633
ChemShuttle	140520	https://www.chemshuttle.com/catalogsearch/result/?q=140520
Excenen	EX-A2214	http://www.excenen.com/searchresultlist.php?id=EX-A2214
KeyOrganics	AS-56097	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-56097
MedChem Express	HY-16294	https://www.medchemexpress.com/search.html?q=HY-16294&ft=&fa=&fp=
MolPort	MolPort-035-944-332	https://www.molport.com/shop/molecule-link/MolPort-035-944-332
Molnova	M15255	https://www.molnova.com/en/serch-list.html?keywords=M15255
MuseChem	I004274	https://www.musechem.com/product/I004274.html
Selleck Chemicals	S7063	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7063
ShangHai Biochempartner	BCP000923	http://www.biochempartner.com/search_BCP000923
ShangHai Biochempartner	BCP07855	http://www.biochempartner.com/search_BCP07855
TargetMol	T1755	https://www.targetmol.com/search?keyword=T1755
Tetrahedron	TS94792	http://www.thsci.com/search.do?q=TS94792
eMolecules	252349374	https://orderbb.emolecules.com/search/#?query=252349374
eMolecules	49572923	https://orderbb.emolecules.com/search/#?query=49572923
mcule	MCULE-3636467091	https://mcule.com/MCULE-3636467091/

PubMed

Title	Date	PubMed
GSK-3: tricks of the trade for a multi-tasking kinase.	2003 Apr 1	12615961
Substituted 3-imidazo[1,2-a]pyridin-3-yl- 4-(1,2,3,4-tetrahydro-[1,4]diazepino-[6,7,1-hi]indol-7-yl)pyrrole-2,5-diones as highly selective and potent inhibitors of glycogen synthase kinase-3.	2004 Jul 29	15267232
Glycogen synthase kinase-3 (GSK3): inflammation, diseases, and therapeutics.	2007 Apr-May	16944320
Fragment and knowledge-based design of selective GSK-3beta inhibitors using virtual screening models.	2009 Jun	18929433

Patents

Sample Use Guides

In Vivo Use Guide

In clinical trial agaisnt AML 40mg LY2090314 was administered intravenously on days 1, 8 and 15 of a 28 day cycle.

Route of Administration: Intravenous

In Vitro Use Guide

Inhibition of GSK3-alpha was determined in biochemical assay. A standard filter binding protocol was used measuring the ability of recombinant GSK3-alpha to phosphorylate phospho-CREB (cAMP response element binding protein) at serine-129 with ATP[gamma-33P] in the presence of test compound.

Name

Type

Language

LY-2090314

Code

English

LY2090314

Code

English

LY 2090314 [WHO-DD]

Common Name

English

1H-PYRROLE-2,5-DIONE, 3-(9-FLUORO-1,2,3,4-TETRAHYDRO-2-(1-PIPERIDINYLCARBONYL)PYRROLO(3,2,1-JK)(1,4)BENZODIAZEPIN-7-YL)-4-IMIDAZO(1,2-A)PYRIDIN-3-YL-

Systematic Name

English

PYRROLO(3,2,1-JK)(1,4)BENZODIAZEPINE, 7-(2,5-DIHYDRO-4-IMIDAZO(1,2-A)PYRIDIN-3-YL-2,5-DIOXO-1H-PYRROL-3-YL)-9-FLUORO-1,2,3,4-TETRAHYDRO-2-(1-PIPERIDINYLCARBONYL)-

Systematic Name

English

Code System Code Type Description

NCI_THESAURUS

C116849