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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.

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
949 ng/mL
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
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
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
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
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
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



OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Discovery of novel AKT inhibitors with enhanced anti-tumor effects in combination with the MEK inhibitor.
2014
A phase IIa study of afuresertib, an oral pan-AKT inhibitor, in patients with Langerhans cell histiocytosis.
2017 May
Patents

Sample Use Guides

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
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 GMT 2023
Edited
by admin
on Fri Dec 15 17:28:16 GMT 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 GMT 2023 , Edited by admin on Fri Dec 15 17:28:16 GMT 2023
Code System Code Type Description
USAN
ZZ-02
Created by admin on Fri Dec 15 17:28:16 GMT 2023 , Edited by admin on Fri Dec 15 17:28:16 GMT 2023
PRIMARY
SMS_ID
100000168977
Created by admin on Fri Dec 15 17:28:16 GMT 2023 , Edited by admin on Fri Dec 15 17:28:16 GMT 2023
PRIMARY
INN
9666
Created by admin on Fri Dec 15 17:28:16 GMT 2023 , Edited by admin on Fri Dec 15 17:28:16 GMT 2023
PRIMARY
PUBCHEM
46843057
Created by admin on Fri Dec 15 17:28:16 GMT 2023 , Edited by admin on Fri Dec 15 17:28:16 GMT 2023
PRIMARY
NCI_THESAURUS
C82390
Created by admin on Fri Dec 15 17:28:16 GMT 2023 , Edited by admin on Fri Dec 15 17:28:16 GMT 2023
PRIMARY
EPA CompTox
DTXSID60146711
Created by admin on Fri Dec 15 17:28:16 GMT 2023 , Edited by admin on Fri Dec 15 17:28:16 GMT 2023
PRIMARY
DRUG BANK
DB11648
Created by admin on Fri Dec 15 17:28:16 GMT 2023 , Edited by admin on Fri Dec 15 17:28:16 GMT 2023
PRIMARY
EVMPD
SUB182525
Created by admin on Fri Dec 15 17:28:16 GMT 2023 , Edited by admin on Fri Dec 15 17:28:16 GMT 2023
PRIMARY
CAS
1047644-62-1
Created by admin on Fri Dec 15 17:28:16 GMT 2023 , Edited by admin on Fri Dec 15 17:28:16 GMT 2023
PRIMARY
FDA UNII
8739X25QI3
Created by admin on Fri Dec 15 17:28:16 GMT 2023 , Edited by admin on Fri Dec 15 17:28:16 GMT 2023
PRIMARY
ChEMBL
CHEMBL2219422
Created by admin on Fri Dec 15 17:28:16 GMT 2023 , Edited by admin on Fri Dec 15 17:28:16 GMT 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY