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Details

Stereochemistry ACHIRAL
Molecular Formula C29H34Cl2N6O3S2
Molecular Weight 649.655
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AVATROMBOPAG

SMILES

OC(=O)C1CCN(CC1)C2=NC=C(C=C2Cl)C(=O)NC3=NC(C4=CC(Cl)=CS4)=C(S3)N5CCN(CC5)C6CCCCC6

InChI

InChIKey=OFZJKCQENFPZBH-UHFFFAOYSA-N
InChI=1S/C29H34Cl2N6O3S2/c30-20-15-23(41-17-20)24-27(37-12-10-35(11-13-37)21-4-2-1-3-5-21)42-29(33-24)34-26(38)19-14-22(31)25(32-16-19)36-8-6-18(7-9-36)28(39)40/h14-18,21H,1-13H2,(H,39,40)(H,33,34,38)

HIDE SMILES / InChI

Molecular Formula C29H34Cl2N6O3S2
Molecular Weight 649.655
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Avatrombopag is an orally bioavailable, small molecule thrombopoietin (TPO) receptor agonist that stimulates proliferation and differentiation of megakaryocytes from bone marrow progenitor cells resulting in increased production of platelets. Avatrombopag does not compete with TPO for binding to the TPO receptor and has an additive effect with TPO on platelet production. Avatrombopag was discovered by Yamanouchi Pharmaceutical, developed by AkaRx which late became acquired by Dova Pharmaceuticals. In 2018 avatrombopag was approved by the FDA for thrombocytopenia in adults with chronic liver disease scheduled to undergo a procedure.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
3.3 nM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
DOPTELET
PubMed

PubMed

TitleDatePubMed
AKR-501 (YM477) in combination with thrombopoietin enhances human megakaryocytopoiesis.
2008 Oct
AKR-501 (YM477) a novel orally-active thrombopoietin receptor agonist.
2009 Apr
Romiplostim: a second-generation thrombopoietin agonist.
2009 Mar
Patents

Patents

Sample Use Guides

In Vivo Use Guide
For patients with a platelet count 40000 to <50000/mm3: 40 mg once daily for 5 consecutive days, orally. For patients with platelet count below 40,000/mm3: 60 mg once daily for 5 consecutive days.
Route of Administration: Oral
In Vitro Use Guide
Avatrombopag stimulated the proliferation of cells expressing the human thrombopoietin receptor (c-Mpl) with an EC50 value of 3.3 nM and promoted the differentiation of human hematopoietic progenitor cells (cord blood CD34+ cells) to megakaryocytes with an EC50 value of 25.0 nM.
Substance Class Chemical
Created
by admin
on Mon Oct 21 23:25:30 UTC 2019
Edited
by admin
on Mon Oct 21 23:25:30 UTC 2019
Record UNII
3H8GSZ4SQL
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AVATROMBOPAG
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
YM€?301477
Common Name English
AVATROMBOPAG [INN]
Common Name English
AVATROMBOPAG [WHO-DD]
Common Name English
AKR-501
Common Name English
YM-477
Code English
AVATROMBOPAG [USAN]
Common Name English
E5501
Code English
E-5501
Code English
E 5501
Common Name English
1-(3-CHLORO-5-((4-(4-CHLOROTHIOPHEN-2-YL)-5-(4-CYCLOHEXYLPIPERAZIN-1-YL)THIAZOL-2-YL)CARBAMOYL)PYRIDIN-2-YL)PIPERIDINE-4-CARBOXYLIC ACID
Systematic Name English
1-(3-CHLORO-5-((4-(4-CHLOROTHIOPHEN-2-YL)-5-(4-CYCLOHEXYLPIPERAZIN-1-YL)THIAZOL-2-YL)CARBAMOYL)-2-PYRIDYL)PIPERIDINE-4-CARBOXYLIC ACID
Systematic Name English
Classification Tree Code System Code
WHO-ATC B02BX08
Created by admin on Mon Oct 21 23:25:30 UTC 2019 , Edited by admin on Mon Oct 21 23:25:30 UTC 2019
NCI_THESAURUS C78275
Created by admin on Mon Oct 21 23:25:30 UTC 2019 , Edited by admin on Mon Oct 21 23:25:30 UTC 2019
Code System Code Type Description
PUBCHEM
9852519
Created by admin on Mon Oct 21 23:25:30 UTC 2019 , Edited by admin on Mon Oct 21 23:25:30 UTC 2019
PRIMARY
INN
9571
Created by admin on Mon Oct 21 23:25:30 UTC 2019 , Edited by admin on Mon Oct 21 23:25:30 UTC 2019
PRIMARY
CAS
570406-98-3
Created by admin on Mon Oct 21 23:25:30 UTC 2019 , Edited by admin on Mon Oct 21 23:25:30 UTC 2019
PRIMARY
EVMPD
SUB121659
Created by admin on Mon Oct 21 23:25:30 UTC 2019 , Edited by admin on Mon Oct 21 23:25:30 UTC 2019
PRIMARY
NCI_THESAURUS
C150559
Created by admin on Mon Oct 21 23:25:30 UTC 2019 , Edited by admin on Mon Oct 21 23:25:30 UTC 2019
PRIMARY
EPA CompTox
570406-98-3
Created by admin on Mon Oct 21 23:25:30 UTC 2019 , Edited by admin on Mon Oct 21 23:25:30 UTC 2019
PRIMARY
ChEMBL
CHEMBL2103883
Created by admin on Mon Oct 21 23:25:30 UTC 2019 , Edited by admin on Mon Oct 21 23:25:30 UTC 2019
PRIMARY
Related Record Type Details
TRANSPORTER -> INHIBITOR
IC50
EXCRETED UNCHANGED
FECAL
METABOLIC ENZYME -> INDUCER
WEAK
METABOLIC ENZYME -> SUBSTRATE
TARGET->IMAGING AGENT
METABOLIC ENZYME -> INDUCER
In vitro data suggests that avatrombopag weakly induces CYP2C8 and CYP2C9
WEAK
TRANSPORTER -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
BINDER->LIGAND
BINDING
TRANSPORTER -> INHIBITOR
IC50
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
Tmax PHARMACOKINETIC
Blood-to-Plasma Ratio PHARMACOKINETIC