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Details

Stereochemistry ABSOLUTE
Molecular Formula C26H27FN10
Molecular Weight 498.558
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AVAPRITINIB

SMILES

CN1C=C(C=N1)C2=CN3N=CN=C(N4CCN(CC4)C5=NC=C(C=N5)[C@@](C)(N)C6=CC=C(F)C=C6)C3=C2

InChI

InChIKey=DWYRIWUZIJHQKQ-SANMLTNESA-N
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

HIDE SMILES / InChI

Molecular Formula C26H27FN10
Molecular Weight 498.558
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Blu-285 is a potent and selective inhibitor for hematologic malignancies with KIT Exon 17 Mutations. BLU-285 has demonstrated biochemical in vitro activity on the KIT exon-17 mutant enzyme, KIT D816V. Cellular activity of BLU-285 on KIT D816 mutants was measured by autophosphorylation in the human mast cell leukemia cell line HMC1.2, and the P815 mouse mastocytoma cell line with IC50= 4 and 22 nM, respectively. In vivo BLU-285 was well tolerated and has demonstrated dose-dependent antitumor efficacy. Complete tumor growth inhibition and ≥ 75% KIT kinase inhibition was observed with 10 mg/kg once daily, oral dosing of BLU-285 in the aggressive KIT exon 17 mutant driven P815 mastocytoma model grown as a solid tumor allograft as well as in a disseminated model of the disease. BLU-285 was also well tolerated in this in vivo model and had no adverse effects on body weight at either dose.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.27 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Patents

Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: Complete tumor growth inhibition and ≥ 75% KIT kinase inhibition was observed with 10 mg/kg once daily, oral dosing of BLU-285 in the aggressive KIT exon 17 mutant driven P815 mastocytoma model grown as a solid tumor allograft as well as in a disseminated model of disease.
BLU-285 capsules or tablets for oral administration. BLU-285 will be dosed daily for 28 day cycles.
Route of Administration: Oral
Cellular activity of BLU-285 on KIT D816 mutants was measured by autophosphorylation in the human mast cell leukemia cell line HMC1.2, and the P815 mouse mastocytoma cell line with IC50= 4 and 22 nM, respectively.
Substance Class Chemical
Created
by admin
on Sun Dec 18 06:48:20 UTC 2022
Edited
by admin
on Sun Dec 18 06:48:20 UTC 2022
Record UNII
513P80B4YJ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AVAPRITINIB
USAN   INN  
Official Name English
X-720776
Code English
AYVAKIT
Brand Name English
70C366
Code English
AVAPRITINIB [MI]
Common Name English
C-366
Code English
(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-YL)PYRIMIDIN-5-YL)ETHAN-1-AMINE
Systematic Name English
AVAPRITINIB [ORANGE BOOK]
Common Name English
5-PYRIMIDINEMETHANAMINE, .ALPHA.-(4-FLUOROPHENYL)-.ALPHA.-METHYL-2-(4-(6-(1-METHYL-1H-PYRAZOL-4-YL)PYRROLO(2,1-F)(1,2,4)TRIAZIN-4-YL)-1-PIPERAZINYL)-, (.ALPHA.S)-
Systematic Name English
Avapritinib [WHO-DD]
Common Name English
BLU-285
Code English
X720776
Code English
avapritinib [INN]
Common Name English
AVAPRITINIB [USAN]
Common Name English
(1S)-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)ethan-1-amine
Systematic Name English
Classification Tree Code System Code
EU-Orphan Drug EU/3/18/2074
Created by admin on Sun Dec 18 06:48:21 UTC 2022 , Edited by admin on Sun Dec 18 06:48:21 UTC 2022
FDA ORPHAN DRUG 506515
Created by admin on Sun Dec 18 06:48:21 UTC 2022 , Edited by admin on Sun Dec 18 06:48:21 UTC 2022
FDA ORPHAN DRUG 500415
Created by admin on Sun Dec 18 06:48:21 UTC 2022 , Edited by admin on Sun Dec 18 06:48:21 UTC 2022
Code System Code Type Description
CAS
1703793-34-3
Created by admin on Sun Dec 18 06:48:21 UTC 2022 , Edited by admin on Sun Dec 18 06:48:21 UTC 2022
PRIMARY
WIKIPEDIA
Avapritinib
Created by admin on Sun Dec 18 06:48:21 UTC 2022 , Edited by admin on Sun Dec 18 06:48:21 UTC 2022
PRIMARY
PUBCHEM
118023034
Created by admin on Sun Dec 18 06:48:21 UTC 2022 , Edited by admin on Sun Dec 18 06:48:21 UTC 2022
PRIMARY
EPA CompTox
DTXSID301027935
Created by admin on Sun Dec 18 06:48:21 UTC 2022 , Edited by admin on Sun Dec 18 06:48:21 UTC 2022
PRIMARY
DAILYMED
513P80B4YJ
Created by admin on Sun Dec 18 06:48:21 UTC 2022 , Edited by admin on Sun Dec 18 06:48:21 UTC 2022
PRIMARY
DRUG CENTRAL
5379
Created by admin on Sun Dec 18 06:48:21 UTC 2022 , Edited by admin on Sun Dec 18 06:48:21 UTC 2022
PRIMARY
DRUG BANK
DB15233
Created by admin on Sun Dec 18 06:48:21 UTC 2022 , Edited by admin on Sun Dec 18 06:48:21 UTC 2022
PRIMARY
RXCUI
2272107
Created by admin on Sun Dec 18 06:48:21 UTC 2022 , Edited by admin on Sun Dec 18 06:48:21 UTC 2022
PRIMARY
USAN
FG-25
Created by admin on Sun Dec 18 06:48:21 UTC 2022 , Edited by admin on Sun Dec 18 06:48:21 UTC 2022
PRIMARY
LACTMED
Avapritinib
Created by admin on Sun Dec 18 06:48:21 UTC 2022 , Edited by admin on Sun Dec 18 06:48:21 UTC 2022
PRIMARY
FDA UNII
513P80B4YJ
Created by admin on Sun Dec 18 06:48:21 UTC 2022 , Edited by admin on Sun Dec 18 06:48:21 UTC 2022
PRIMARY
NCI_THESAURUS
C123827
Created by admin on Sun Dec 18 06:48:21 UTC 2022 , Edited by admin on Sun Dec 18 06:48:21 UTC 2022
PRIMARY
INN
10613
Created by admin on Sun Dec 18 06:48:21 UTC 2022 , Edited by admin on Sun Dec 18 06:48:21 UTC 2022
PRIMARY
MERCK INDEX
M12190
Created by admin on Sun Dec 18 06:48:21 UTC 2022 , Edited by admin on Sun Dec 18 06:48:21 UTC 2022
PRIMARY
Related Record Type Details
OFF-TARGET->INHIBITOR
>100× the free mean maximum plasma concentration at steady state [Cmax,ss] of 0.022 µM at the MTD in humans of 400 mg QD
IC50
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EXCRETED UNCHANGED
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AMOUNT EXCRETED
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METABOLIC ENZYME -> INHIBITOR
EXCRETED UNCHANGED
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AMOUNT EXCRETED
FECAL
METABOLIC ENZYME -> SUBSTRATE
MINOR
BINDER->LIGAND
BINDING
TARGET -> INHIBITOR
IC50
METABOLIC ENZYME -> INHIBITOR
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TIME-DEPENDENT INHIBITION
Ki
METABOLIC ENZYME -> INHIBITOR
COMPETITIVE INHIBITOR
Ki
METABOLIC ENZYME -> SUBSTRATE
MAJOR
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC SINGLE DOSE ADMINISTRATION

blood-to-plasma ratio PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC SINGLE DOSE ADMINISTRATION

Volume of Distribution PHARMACOKINETIC