Details of the Drug

General Information of Drug (ID: DMV05SW)

Drug Name

As-1670542

Synonyms

AVATROMBOPAG; 570406-98-3; AKR-501; UNII-3H8GSZ4SQL; 3H8GSZ4SQL; AKR 501; Avatrombopag [USAN:INN]; Doptelet; AS 1670542; Avatrombopag (USAN/INN); GTPL9953; DTXSID30205667; ZINC72190218; AKOS027323962; CS-3397; HY-13463; FT-0728753; D10306; AS1670542

Indication

Disease Entry	ICD 11	Status	REF
Thrombocytopenia	3B64	Approved	[1]
Idiopathic thrombocytopenic purpura	3B64.10	Phase 3	[2]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

649.7

Topological Polar Surface Area (xlogp)

4

Rotatable Bond Count (rotbonds)

7

Hydrogen Bond Donor Count (hbonddonor)

2

Hydrogen Bond Acceptor Count (hbondacc)

10

ADMET Property

Absorption Tmax: The time to maximum plasma concentration (Tmax) is 5-8 h [3]
Clearance: The clearance of drug is 6.9 L/h [4]
Elimination: Fecal excretion accounted for 88% of the administered dose, with 34% of the dose excreted as unchanged avatrombopag, and only 6% of the administered dose was found in urine [4]
Half-life: The concentration or amount of drug in body reduced by one-half in 19 hours [5]
Metabolism: The drug is metabolized via the cytochrome P450 (CYP) 2C9 and CYP3A4 [5]
Vd: The volume of distribution (Vd) of drug is 180 L [4]

Chemical Identifiers

Formula: C29H34Cl2N6O3S2
IUPAC Name: 1-[3-chloro-5-[[4-(4-chlorothiophen-2-yl)-5-(4-cyclohexylpiperazin-1-yl)-1,3-thiazol-2-yl]carbamoyl]pyridin-2-yl]piperidine-4-carboxylic acid
Canonical SMILES: C1CCC(CC1)N2CCN(CC2)C3=C(N=C(S3)NC(=O)C4=CC(=C(N=C4)N5CCC(CC5)C(=O)O)Cl)C6=CC(=CS6)Cl
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)
InChIKey: OFZJKCQENFPZBH-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 9852519
CAS Number: 570406-98-3
DrugBank ID: DB11995
TTD ID: D0W1DI
ACDINA ID: D00852

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Thrombopoietin receptor (MPL)	TTIHYA4	TPOR_HUMAN	Agonist	[6]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

ICD Disease Classification

03 Disease of the blood or blood-forming organs

Disease Class

ICD-11: 3B64 Thrombocytopenia

The Studied Tissue

Whole blood

The Studied Disease

Thrombocytopenia [ICD-11:3B64]

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Thrombopoietin receptor (MPL)	DTT	MPL	8.96E-01	0.07	0.28

Molecular Expression Atlas (MEA)

MEA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from As-1670542 (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Gilteritinib	DMWQ4MZ	Moderate	Decreased clearance of As-1670542 due to the transporter inhibition by Gilteritinib.	Acute myeloid leukaemia [2A60]	[12]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of As-1670542 caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[13]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Crospovidone	E00626	Not Available	Disintegrant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 4000	E00654	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyvinyl alcohol	E00666	Not Available	Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Hydrophobic colloidal silica	E00285	24261	Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
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⏷ Show the Full List of 10 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Avatrombopag 20 mg tablet	20 mg	Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
2	ClinicalTrials.gov (NCT01433978) A Phase 3, Multicenter, Randomized, Double-blind, Active-controlled, Parallel-group Trial With an Open-label Extension Phase to Evaluate the Efficacy and Safety of Oral E5501 Versus Eltrombopag, in Adults With Chronic Immune Thrombocytopenia (Idiopathic Thrombocytopenic Purpura). U.S. National Institutes of Health.
3	Nomoto M, Pastino G, Rege B, Aluri J, Ferry J, Han D: Pharmacokinetics, Pharmacodynamics, Pharmacogenomics, Safety, and Tolerability of Avatrombopag in Healthy Japanese and White Subjects. Clin Pharmacol Drug Dev. 2018 Feb;7(2):188-195. doi: 10.1002/cpdd.349. Epub 2017 Mar 24.
4	An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
5	FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
6	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1722).
7	2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
8	Emerging drugs for idiopathic thrombocytopenic purpura in adults. Expert Opin Emerg Drugs. 2008 Jun;13(2):237-54.
9	Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
10	A novel nonpeptidyl human c-Mpl activator stimulates human megakaryopoiesis and thrombopoiesis. Blood. 2006 Jun 1;107(11):4300-7.
11	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
12	Cerner Multum, Inc. "Australian Product Information.".
13	Product Information. Sonata (zaleplon) Wyeth-Ayerst Laboratories, Philadelphia, PA.