GSK-2256294

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H24F3N7O
Molecular Weight	447.4568
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CNC1=NC(N[C@H]2CCC[C@H](C2)C(=O)NCC3=CC=C(C=C3C(F)(F)F)C#N)=NC(C)=N1

InChI

InChIKey=LQHDJQIMETZMPH-ZBFHGGJFSA-N

InChI=1S/C21H24F3N7O/c1-12-28-19(26-2)31-20(29-12)30-16-5-3-4-14(9-16)18(32)27-11-15-7-6-13(10-25)8-17(15)21(22,23)24/h6-8,14,16H,3-5,9,11H2,1-2H3,(H,27,32)(H2,26,28,29,30,31)/t14-,16+/m1/s1

HIDE SMILES / InChI

Molecular Formula	C21H24F3N7O
Molecular Weight	447.4568
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/27884766
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23434473

GSK-2256294 is a potent, reversible, tight binding inhibitor of isolated recombinant human sEH (soluble epoxide hydrolase) (IC50 = 27 pM; t1/2 = 121 min) and displays potent inhibition against the rat (IC50 = 61 pM) and murine (IC50 = 189 pM) orthologs of sEH. GSK-2256294A also displays potent cellular inhibition (IC50 = 0.66 nM) of sEH in an assay developed using a cell line transfected with the human sEH enzyme. GSK-2256294 was well-tolerated and demonstrated sustained inhibition of sEH enzyme activity. These data support further investigation in patients with endothelial dysfunction or abnormal tissue repair, such as diabetes, wound healing or COPD. GSK-2256294 is in phase I clinical trials for the treatment of COPD.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Epoxide hydratase 4 Target ID: CHEMBL2409 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23434473	Inhibitor 8297		27.0 pM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pulmonary disease, chronic obstructive 3 Sources: https://clinicaltrials.gov/ct2/show/NCT01762774	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
1223 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26620151	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	GSK-2256294 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN
1455 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26620151	18 mg 1 times / day multiple, oral dose: 18 mg route of administration: Oral experiment type: MULTIPLE co-administered:	GSK-2256294 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN
321 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26620151	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	GSK-2256294 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
559 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26620151	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	GSK-2256294 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN
689 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26620151	6 mg 1 times / day multiple, oral dose: 6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	GSK-2256294 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN
836 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26620151	12 mg single, oral dose: 12 mg route of administration: Oral experiment type: SINGLE co-administered:	GSK-2256294 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
11464 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26620151	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	GSK-2256294 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN
15774 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26620151	18 mg 1 times / day multiple, oral dose: 18 mg route of administration: Oral experiment type: MULTIPLE co-administered:	GSK-2256294 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN
2741 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26620151	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	GSK-2256294 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
5267 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26620151	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	GSK-2256294 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN
5801 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26620151	6 mg 1 times / day multiple, oral dose: 6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	GSK-2256294 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN
6680 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26620151	12 mg single, oral dose: 12 mg route of administration: Oral experiment type: SINGLE co-administered:	GSK-2256294 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
41.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26620151	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	GSK-2256294 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN
25 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26620151	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	GSK-2256294 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
42.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26620151	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	GSK-2256294 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN
19.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26620151	12 mg single, oral dose: 12 mg route of administration: Oral experiment type: SINGLE co-administered:	GSK-2256294 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 1537

Drug as perpetrator

Target	Modality	Activity
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=440681560	inconclusive [IC50 21.3174 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=440681560	no
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=440681560	yes [IC50 9.5221 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363680418	no

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY34458	https://www.001chemical.com/chem/search?q=DY34458
1PlusChem LLC	1P008U49	https://www.1pchem.com/search?query=1P008U49
Axon MedChem	2220	https://www.axonmedchem.com/product/2220
BLD Pharm	BD629930	http://www.bldpharm.com/search/Search.html?keyword=BD629930
Chem Scene	CS-5395	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-5395
MedChem Express	HY-19644	https://www.medchemexpress.com/search.html?q=HY-19644&ft=&fa=&fp=
MolPort	MolPort-042-665-838	https://www.molport.com/shop/molecule-link/MolPort-042-665-838
Molcore	MC34458	http://www.molcore.com/CatMC34458.html
Ryan Scientific	101-94179	https://ryansci.com/products?q=101-94179&list_q=&search_type=exact
Toronto Research Chemicals	G797420	https://www.trc-canada.com/product-detail/?CatNum=G797420
eMolecules	275108999	https://orderbb.emolecules.com/search/#?query=275108999
eMolecules	301048969	https://orderbb.emolecules.com/search/#?query=301048969
eMolecules	49435320	https://orderbb.emolecules.com/search/#?query=49435320
mcule	MCULE-6540455969	https://mcule.com/MCULE-6540455969/

PubMed

Title	Date	PubMed

Patents

Sample Use Guides

In Vivo Use Guide

GSK-2256294 capsules will be administered as once daily as single dose 2 mg, 6 mg, 15 mg in Cohort 1 and 15 mg, 40 mg, 100 mg in Cohort 2. GSK-2256294 capsules will be administered once or twice daily (cohorts 3 and 4) at the dose determined from the data from Cohort 1 and 2.

Route of Administration: Oral

In Vitro Use Guide

GSK-2256294 displays potent cellular inhibition (IC50 = 0.66 nM) of sEH in an assay developed using HEK-293 cells transfected with the human sEH enzyme.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 10:55:32 GMT 2023` Edited by `admin` on `Sat Dec 16 10:55:32 GMT 2023`
Record UNII	L33EX3XR0T
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

GSK-2256294

Code

English

CYCLOHEXANECARBOXAMIDE, N-((4-CYANO-2-(TRIFLUOROMETHYL)PHENYL)METHYL)-3-((4-METHYL-6-(METHYLAMINO)-1,3,5-TRIAZIN-2-YL)AMINO)-, (1R,3S)-

Systematic Name

English

GSK2256294

Code

English

GSK-2256294A

Code

English

Code System Code Type Description

CAS

1142090-23-0

Created by admin on Sat Dec 16 10:55:32 GMT 2023 , Edited by admin on Sat Dec 16 10:55:32 GMT 2023

PRIMARY

PUBCHEM

59448236

Created by admin on Sat Dec 16 10:55:32 GMT 2023 , Edited by admin on Sat Dec 16 10:55:32 GMT 2023

PRIMARY

SMS_ID

300000042357

Created by admin on Sat Dec 16 10:55:32 GMT 2023 , Edited by admin on Sat Dec 16 10:55:32 GMT 2023

PRIMARY

FDA UNII

L33EX3XR0T

Created by admin on Sat Dec 16 10:55:32 GMT 2023 , Edited by admin on Sat Dec 16 10:55:32 GMT 2023

PRIMARY

Related Record Type Details


					JEH09DQZ6V

BIFUNCTIONAL EPOXIDE HYDROLASE 2

TARGET -> INHIBITOR

Amount:

Related Record Type Details


					L33EX3XR0T

GSK-2256294

ACTIVE MOIETY

Amount:

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/27884766Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23434473

Originator

Approval Year

Targets

Conditions

Approved Use

Cmax

AUC

T1/2

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27884766
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23434473

C_max

T_1/2

Drug as perpetrator