Details of the Drug

General Information of Drug (ID: DMK2GZX)

Drug Name

Avapritinib

Synonyms

1703793-34-3; UNII-513P80B4YJ; 513P80B4YJ; (1S)-1-(4-fluorophenyl)-1-[2-[4-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]piperazin-1-yl]pyrimidin-5-yl]ethanamine; Avapritinib [INN]; BLU-285 (Avapritinib); SCHEMBL16652297; EX-A1366; BCP20175; CS-7577; ACN-051245; HY-101561; (S)-1-(4-fluorophenyl)-1-(2-(4-(6-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl)piperazin-1-yl)pyrimidin-5-yl)ethanamine

Indication

Disease Entry	ICD 11	Status	REF
Gastrointestinal stromal tumour	2B5B	Approved	[1]
Mast cell leukaemia	2A21.00	Phase 1	[2]
Systemic mastocytosis	2A21.0	Phase 1	[3]

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

498.6

Topological Polar Surface Area (xlogp)

1.9

Rotatable Bond Count (rotbonds)

5

Hydrogen Bond Donor Count (hbonddonor)

1

Hydrogen Bond Acceptor Count (hbondacc)

9

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 15400 mcgh/L [4]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 813 mcg/L [4]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 2-4.1 h [4]
Clearance: The apparent oral clearance of drug is 19.5 L/h [4]
Elimination: Avapritinib is 70% eliminated in the feces with 11% as the unchanged drug and 18% eliminated in the urine with 0.23% as the unchanged drug [4]
Half-life: The concentration or amount of drug in body reduced by one-half in 32 - 57 hours [4]
Metabolism: The drug is metabolized via the CYP3A4 and CYP2C9 in vitro [4]
Vd: The volume of distribution (Vd) of drug is 1200 L [4]

Chemical Identifiers

Formula: C26H27FN10
IUPAC Name: (1S)-1-(4-fluorophenyl)-1-[2-[4-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]piperazin-1-yl]pyrimidin-5-yl]ethanamine
Canonical SMILES: C[C@](C1=CC=C(C=C1)F)(C2=CN=C(N=C2)N3CCN(CC3)C4=NC=NN5C4=CC(=C5)C6=CN(N=C6)C)N
InChI: InChI=1S/C26H27FN10/c1-26(28,20-3-5-22(27)6-4-20)21-13-29-25(30-14-21)36-9-7-35(8-10-36)24-23-11-18(16-37(23)33-17-31-24)19-12-32-34(2)15-19/h3-6,11-17H,7-10,28H2,1-2H3/t26-/m0/s1
InChIKey: DWYRIWUZIJHQKQ-SANMLTNESA-N

Cross-matching ID

PubChem CID: 118023034
CAS Number: 1703793-34-3
DrugBank ID: DB15233
TTD ID: D0UO2P
ACDINA ID: D01518

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Platelet-derived growth factor receptor alpha (PDGFRA)	TT8FYO9	PGFRA_HUMAN	Inhibitor	[1]

------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Gastrointestinal stromal tumour

ICD Disease Classification

2B5B

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Platelet-derived growth factor receptor alpha (PDGFRA)	DTT	PDGFRA	3.46E-01	-0.23	-1.55

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Avapritinib (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Selpercatinib	DMZR15V	Moderate	Decreased metabolism of Avapritinib caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[15]
-----------

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Carmellose sodium	E00625	Not Available	Disintegrant
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
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
Copovidone	E00693	Not Available	Film/membrane-forming agent; Modified-release agent; Binding agent
--------------------


⏷ Show the Full List of 8 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Vapritinib 200mg tablet	200mg	Tablet	Oral
Vapritinib 300mg tablet	300mg	Tablet	Oral
Vapritinib 100mg tablet	100mg	Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
2	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4	FDA Approved Drug Products: Avapritinib Oral Tablets
5	Discovery of 5-[5-fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl]-2,4- dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel... J Med Chem. 2003 Mar 27;46(7):1116-9.
6	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
7	A phase I study of olaratumab, an anti-platelet-derived growth factor receptor alpha (PDGFRalpha) monoclonal antibody, in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Mar;73(3):595-604.
8	E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer Res. 2011 Feb 15;71(4):1396-405.
9	The FLT3 and PDGFR inhibitor crenolanib is a substrate of the multidrug resistance protein ABCB1 but does not inhibit transport function at pharmacologically relevant concentrations.Invest New Drugs.2015 Apr;33(2):300-9.
10	Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
11	National Cancer Institute Drug Dictionary (drug id 452042).
12	Phase 1B study of amuvatinib in combination with five standard cancer therapies in adults with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Jul;74(1):195-204.
13	Clinical pipeline report, company report or official report of MedImmune (2011).
14	RET kinase inhibitors: a review of recent patents (2012-2015).Expert Opin Ther Pat. 2017 Jan;27(1):91-99.
15	Cerner Multum, Inc. "UK Summary of Product Characteristics.".