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]

• ATC Code:
  L01EX18: Avapritinib
  L01EX: Other protein kinase inhibitors
  L01E: PROTEIN KINASE INHIBITORS
  L01: ANTINEOPLASTIC AGENTS
  L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 498.6
  Logarithm of the Partition Coefficient (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
  ChEBI ID: CHEMBL4204794
  CAS Number: 1703793-34-3
  UNII: 513P80B4YJ
  DrugBank ID: DB15233
  TTD ID: D0UO2P
  ACDINA ID: D01518
• Drug-Molecule Activity Atlas (DMA)NEW: Click to Jump to the Detailed DMA Information of This Drug
• Drug ADMET Endpoint Profile (DAE)NEW: Click to Jump to the Detailed DAE Information of This Drug
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

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 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

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]	[5]

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

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] Cerner Multum, Inc. "UK Summary of Product Characteristics.".