avatrombopag   Click here for help

GtoPdb Ligand ID: 9953

Synonyms: AKR-501 [1] | Doptelet® | E5501 [4] | YM477
Approved drug
avatrombopag is an approved drug (FDA (2018), EMA (2019))
Compound class: Synthetic organic
Comment: Avatrombopag is a second generation, small molecule, orally administered thrombopoietin receptor agonist [1]. It was discovered through its ability to mimic the action of endogenous thrombopoietin which is the primary physiological regulator of normal platelet production. The pharmacokinetics, pharmacodynamics, pharmacogenomics, safety, and tolerability of avatrombopag were reported by Nomoto et al. in 2017 [2].

avatrombopag is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 9
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 158.38
Molecular weight 648.15
XLogP 5.6
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES OC(=O)C1CCN(CC1)c1ncc(cc1Cl)C(=O)Nc1sc(c(n1)c1scc(c1)Cl)N1CCN(CC1)C1CCCCC1
Isomeric SMILES OC(=O)C1CCN(CC1)c1ncc(cc1Cl)C(=O)Nc1sc(c(n1)c1scc(c1)Cl)N1CCN(CC1)C1CCCCC1
InChI 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)
InChI Key OFZJKCQENFPZBH-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Avatrombopag is approved by the FDA and EMA as a treatment for thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo elective surgery [3]. FDA approval was expanded in June 2019 to include treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) who have failed to respond effectively to a previous treatment.
Click here to link to the full list of avatrombopag studies that are registered with ClinicalTrials.gov.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Like thrombopoetin, avatrombopag dose-dependently stimulates differentiation of hematopoietic progenitor cells to megakaryocytes, and magakaryocyte polyploidization, which are actions that underlie platelet production [1].
External links Click here for help
For extended ADME data see the following:

Drugs.com
European Medicines Agency (EMA)