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Details

Stereochemistry ACHIRAL
Molecular Formula C29H34Cl2N6O3S2.C4H4O4
Molecular Weight 765.727
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of AVATROMBOPAG MALEATE

SMILES

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

InChI

InChIKey=MISPBGHDNZYFNM-BTJKTKAUSA-N
InChI=1S/C29H34Cl2N6O3S2.C4H4O4/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;5-3(6)1-2-4(7)8/h14-18,21H,1-13H2,(H,39,40)(H,33,34,38);1-2H,(H,5,6)(H,7,8)/b;2-1-

HIDE SMILES / InChI

Molecular Formula C4H4O4
Molecular Weight 116.0722
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Molecular Formula C29H34Cl2N6O3S2
Molecular Weight 649.655
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
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.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
3.3 nM [EC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
DOPTELET

Cmax

ValueDoseCo-administeredAnalytePopulation
284 ng/mL
60 mg single, oral
AVATROMBOPAG plasma
Homo sapiens
388 ng/mL
100 mg single, oral
AVATROMBOPAG plasma
Homo sapiens
95.4 ng/mL
20 mg single, oral
AVATROMBOPAG plasma
Homo sapiens
117 ng/mL
40 mg single, oral
AVATROMBOPAG plasma
Homo sapiens
183 ng/mL
60 mg single, oral
AVATROMBOPAG plasma
Homo sapiens
164 ng/mL
40 mg single, oral
AVATROMBOPAG plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
10000 ng × h/mL
60 mg single, oral
AVATROMBOPAG plasma
Homo sapiens
10863.5 ng × h/mL
100 mg single, oral
AVATROMBOPAG plasma
Homo sapiens
3160 ng × h/mL
20 mg single, oral
AVATROMBOPAG plasma
Homo sapiens
3340 ng × h/mL
40 mg single, oral
AVATROMBOPAG plasma
Homo sapiens
4840 ng × h/mL
60 mg single, oral
AVATROMBOPAG plasma
Homo sapiens
5900 ng × h/mL
40 mg single, oral
AVATROMBOPAG plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
18.2 h
60 mg single, oral
AVATROMBOPAG plasma
Homo sapiens
18 h
100 mg single, oral
AVATROMBOPAG plasma
Homo sapiens
18.6 h
20 mg single, oral
AVATROMBOPAG plasma
Homo sapiens
18 h
40 mg single, oral
AVATROMBOPAG plasma
Homo sapiens

Doses

AEs

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

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
Record UNII
GDW7M2P1IS
Record Status Validated (UNII)
Record Version