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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 of GSK-2256294

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
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

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 27.0 pM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase I
428
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
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

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
1587
inhibitor
1767
inhibitor
1852

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1537
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP2D6
1891
 inconclusive [IC50 21.3174 uM]
CYP2C9
1819
 no
CYP3A4
1925
 yes [IC50 9.5221 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
P-gp
1537
 no
Sourcing

Sourcing

Vendor/AggregatorIDURL
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

PubMed

TitleDatePubMed
Patents

Patents

20100210656
1
20100249137
1
8173805
1
8212032
1
WO2009049157A1
1

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
BIFUNCTIONAL EPOXIDE HYDROLASE 2
TARGET -> INHIBITOR
Related Record Type Details
Structure of GSK-2256294
ACTIVE MOIETY
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