U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C18H17Cl2FN4OS
Molecular Weight 427.323
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AFURESERTIB

SMILES

CN1N=CC(Cl)=C1C2=C(Cl)SC(=C2)C(=O)N[C@H](CN)CC3=CC=CC(F)=C3

InChI

InChIKey=AFJRDFWMXUECEW-LBPRGKRZSA-N
InChI=1S/C18H17Cl2FN4OS/c1-25-16(14(19)9-23-25)13-7-15(27-17(13)20)18(26)24-12(8-22)6-10-3-2-4-11(21)5-10/h2-5,7,9,12H,6,8,22H2,1H3,(H,24,26)/t12-/m0/s1

HIDE SMILES / InChI
Molecular Formula C18H17Cl2FN4OS
Molecular Weight 427.323
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including http://www.bloodjournal.org/content/118/21/1856 http://adisinsight.springer.com/drugs/800033693

Afuresertib (GSK2110183 ) is an orally bioavailable inhibitor of the serine/threonine protein kinase Akt (protein kinase B) with potential antineoplastic activity. Afuresertib binds to and inhibits the activity of Akt, which may result in inhibition of the PI3K/Akt signaling pathway and tumor cell proliferation and the induction of tumor cell apoptosis. Activation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents. Preclinically, AKT inhibition by afuresertib can reverse platinum resistance in ovarian cancer cell lines isolated from patients with platinum-resistant ovarian cancer. Afuresertib is well tolerated and demonstrates clinical activity as monotherapy in heavily pretreated MM patients. Is in phase II clinical trials for Chronic lymphocytic leukaemia; Haematological malignancies; Histiocytosis.

Originator

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 0.08 nM [Ki]
Inhibitor
8297
 2.0 nM [Ki]
Inhibitor
8297
 2.6 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
949 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/25075128/
150 mg 1 times / day multiple, oral
dose: 150 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AFURESERTIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
554 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/25075128/
100 mg 1 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AFURESERTIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
531 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/25075128/
125 mg 1 times / day multiple, oral
dose: 125 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AFURESERTIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
13425 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/25075128/
150 mg 1 times / day multiple, oral
dose: 150 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AFURESERTIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
6782 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/25075128/
100 mg 1 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AFURESERTIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
7405 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/25075128/
125 mg 1 times / day multiple, oral
dose: 125 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AFURESERTIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
1587
inhibitor
1767
inhibitor
1852

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1461

BCRP
699
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
BCRP
773
 no
P-gp
1650
 no
CYP3A4
1925
 yes [IC50 0.3011 uM]
CYP2D6
1891
 yes [IC50 2.6837 uM]
CYP2C9
1819
 yes [IC50 9.5221 uM]
Sourcing

Sourcing

Vendor/AggregatorIDURL
001 Chemical
DY34177
https://www.001chemical.com/chem/search?q=DY34177
1PlusChem LLC
1P008TTY
https://www.1pchem.com/search?query=1P008TTY
1PlusChem LLC
1P008TTZ
https://www.1pchem.com/search?query=1P008TTZ
AChemBlock
L13491
http://www.achemblock.com/catalogsearch/result/?q=L13491
AChemBlock
M15668
http://www.achemblock.com/catalogsearch/result/?q=M15668
Angene
AGN-PC-0WCXBP
http://www.angenechemical.com/productshow/AGN-PC-0WCXBP.html
ApexBio Technology
B4811
https://www.apexbt.com/catalogsearch/result/?q=B4811
AstaTech
P14643
http://astatechinc.com/CPSResult.php?CRNO=P14643
Axon MedChem
2460
https://www.axonmedchem.com/product/2460
BLD Pharm
BD300977
http://www.bldpharm.com/search/Search.html?keyword=BD300977
BLD Pharm
BD629860
http://www.bldpharm.com/search/Search.html?keyword=BD629860
Cayman Chemical
17988
http://www.caymanchem.com/app/template/Product.vm/catalog/17988
Chem Scene
CS-3384
http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3384
Chem Scene
CS-3385
http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3385
ChemShuttle
152015
https://www.chemshuttle.com/catalogsearch/result/?q=152015
Excenen
EX-A1573
http://www.excenen.com/searchresultlist.php?id=EX-A1573
Excenen
EX-A1574
http://www.excenen.com/searchresultlist.php?id=EX-A1574
KeyOrganics
AS-56283
http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-56283
MedChem Express
HY-15727
https://www.medchemexpress.com/search.html?q=HY-15727A&ft=&fa=&fp=
MedChem Express
HY-15727A
https://www.medchemexpress.com/search.html?q=HY-15727A&ft=&fa=&fp=
MolPort
MolPort-039-063-478
https://www.molport.com/shop/molecule-link/MolPort-039-063-478
MolPort
MolPort-039-193-816
https://www.molport.com/shop/molecule-link/MolPort-039-193-816
MolPort
MolPort-042-676-197
https://www.molport.com/shop/molecule-link/MolPort-042-676-197
Molcore
MC34177
http://www.molcore.com/CatMC34177.html
Molnova
M10234
https://www.molnova.com/en/serch-list.html?keywords=M10234
Molnova
M10235
https://www.molnova.com/en/serch-list.html?keywords=M10235
MuseChem
I000266
https://www.musechem.com/product/I000266.html
Ryan Scientific
WH-4-023
https://ryansci.com/products?q=WH-4-023&list_q=&search_type=exact
Selleck Chemicals
S7521
http://www.selleckchem.com/search.html?searchDTO.searchParam=S7521
ShangHai Biochempartner
BCP08435
http://www.biochempartner.com/search_BCP08435
ShangHai Biochempartner
BCP19741
http://www.biochempartner.com/search_BCP19741
TargetMol
T1911
https://www.targetmol.com/search?keyword=T1911
eMolecules
108759016
https://orderbb.emolecules.com/search/#?query=108759016
eMolecules
205748941
https://orderbb.emolecules.com/search/#?query=205748941
eMolecules
301193176
https://orderbb.emolecules.com/search/#?query=301193176
eMolecules
301193432
https://orderbb.emolecules.com/search/#?query=301193432
eMolecules
50282579
https://orderbb.emolecules.com/search/#?query=50282579
eNovation Chemicals
D497621
https://www.enovationchem.com/Products.asp?SEARCHTEXT=D497621&searchbtn.x=0&searchbtn.y=0
eNovation Chemicals
D501891
https://www.enovationchem.com/Products.asp?SEARCHTEXT=D501891&searchbtn.x=0&searchbtn.y=0
mcule
MCULE-4025424570
https://mcule.com/MCULE-4025424570/
mcule
MCULE-4988273902
https://mcule.com/MCULE-4988273902/
mcule
MCULE-5404870108
https://mcule.com/MCULE-5404870108/
mcule
MCULE-8719640373
https://mcule.com/MCULE-8719640373/
PubMed

PubMed

TitleDatePubMed
Discovery of novel AKT inhibitors with enhanced anti-tumor effects in combination with the MEK inhibitor.
2014
Phase I study of the MEK inhibitor trametinib in combination with the AKT inhibitor afuresertib in patients with solid tumors and multiple myeloma.
2015 Jan
A phase IIa study of afuresertib, an oral pan-AKT inhibitor, in patients with Langerhans cell histiocytosis.
2017 May
Patents

Patents

08273782
5
08410158
5
08609711
2
20090209607
4

Sample Use Guides

In Vivo Use Guide
Seventy-three patients were treated at doses ranging from 25 to 150 mg per day. The MTD was established at 125 mg per day
Route of Administration: Oral
In Vitro Use Guide
Afuresertib inhibits the kinase activity of the E17K AKT1 mutant protein with EC50 of 0.2 nM. Afuresertib shows a concentration-dependent effect on multiple AKT substrate phosphorylation levels, including GSK3b, PRAS40, FOXO and Caspase 9. Overall 65% of the hematological cell lines are sensitive to afuresertib (EC50 < 1 uM).
Substance Class Chemical
Created
by admin
on Fri Dec 15 17:28:16 UTC 2023
Edited
by admin
on Fri Dec 15 17:28:16 UTC 2023
Record UNII
8739X25QI3
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AFURESERTIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
ASB-183
Code English
GSK-2110183
Code English
2-THIOPHENECARBOXAMIDE, N-((1S)-2-AMINO-1-((3-FLUOROPHENYL)METHYL)ETHYL)-5-CHLORO-4-(4-CHLORO-1-METHYL-1H-PYRAZOL-5-YL)-
Systematic Name English
GSK2110183
Code English
afuresertib [INN]
Common Name English
N-[(1S)-1-(Aminomethyl)-2-(3-fluorophenyl)ethyl]-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)thiophene-2-carboxamide
Systematic Name English
GSK2110183C
Code English
AFURESERTIB [USAN]
Common Name English
Afuresertib [WHO-DD]
Common Name English
ASB183
Code English
GSK-2110183C
Code English
N-((2S)-1-AMINO-3-(3-FLUOROPHENYL)PROPAN-2-YL)-5-CHLORO-4-(4-CHLORO-1-METHYL-1H-PYRAZOL-5-YL)THIOPHENE-2-CARBOXAMIDE
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C155764
Created by admin on Fri Dec 15 17:28:16 UTC 2023 , Edited by admin on Fri Dec 15 17:28:16 UTC 2023
Code System Code Type Description
USAN
ZZ-02
Created by admin on Fri Dec 15 17:28:16 UTC 2023 , Edited by admin on Fri Dec 15 17:28:16 UTC 2023
PRIMARY
SMS_ID
100000168977
Created by admin on Fri Dec 15 17:28:16 UTC 2023 , Edited by admin on Fri Dec 15 17:28:16 UTC 2023
PRIMARY
INN
9666
Created by admin on Fri Dec 15 17:28:16 UTC 2023 , Edited by admin on Fri Dec 15 17:28:16 UTC 2023
PRIMARY
PUBCHEM
46843057
Created by admin on Fri Dec 15 17:28:16 UTC 2023 , Edited by admin on Fri Dec 15 17:28:16 UTC 2023
PRIMARY
NCI_THESAURUS
C82390
Created by admin on Fri Dec 15 17:28:16 UTC 2023 , Edited by admin on Fri Dec 15 17:28:16 UTC 2023
PRIMARY
EPA CompTox
DTXSID60146711
Created by admin on Fri Dec 15 17:28:16 UTC 2023 , Edited by admin on Fri Dec 15 17:28:16 UTC 2023
PRIMARY
DRUG BANK
DB11648
Created by admin on Fri Dec 15 17:28:16 UTC 2023 , Edited by admin on Fri Dec 15 17:28:16 UTC 2023
PRIMARY
EVMPD
SUB182525
Created by admin on Fri Dec 15 17:28:16 UTC 2023 , Edited by admin on Fri Dec 15 17:28:16 UTC 2023
PRIMARY
CAS
1047644-62-1
Created by admin on Fri Dec 15 17:28:16 UTC 2023 , Edited by admin on Fri Dec 15 17:28:16 UTC 2023
PRIMARY
FDA UNII
8739X25QI3
Created by admin on Fri Dec 15 17:28:16 UTC 2023 , Edited by admin on Fri Dec 15 17:28:16 UTC 2023
PRIMARY
ChEMBL
CHEMBL2219422
Created by admin on Fri Dec 15 17:28:16 UTC 2023 , Edited by admin on Fri Dec 15 17:28:16 UTC 2023
PRIMARY
Related Record Type Details
Structure of AFURESERTIB HYDROCHLORIDE
SALT/SOLVATE -> PARENT
RAC-ALPHA SERINE/THREONINE-PROTEIN KINASE
TARGET -> INHIBITOR
Related Record Type Details
Structure of AFURESERTIB
ACTIVE MOIETY
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966