MIVAVOTINIB CITRATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H21FN6O.C6H8O7
Molecular Weight	536.5102
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)CC(O)(CC(O)=O)C(O)=O.CN1C=C(C=N1)C2=C3C(=O)NCC3=C(F)C(N[C@@H]4CCCC[C@@H]4N)=N2

InChI

InChIKey=ZVPYVZMKBQYKQG-ZVWHLABXSA-N

InChI=1S/C17H21FN6O.C6H8O7/c1-24-8-9(6-21-24)15-13-10(7-20-17(13)25)14(18)16(23-15)22-12-5-3-2-4-11(12)19;7-3(8)1-6(13,5(11)12)2-4(9)10/h6,8,11-12H,2-5,7,19H2,1H3,(H,20,25)(H,22,23);13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)/t11-,12+;/m0./s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/30135222 | https://www.ncbi.nlm.nih.gov/pubmed/28754125 | https://www.ncbi.nlm.nih.gov/pubmed/28754125

TAK-659 is an investigational, reversible, and potent dual inhibitor of SYK and FLT-3 kinases. TAK-659 inhibited the pro-survival, proliferative, chemoresistant, and activation effects promoted by the microenvironment. Combination of TAK-659 with other BCR inhibitors showed a synergistic effect in inducing apoptosis. Combination of TAK-659 and ibrutinib induced significantly higher cytotoxicity toward CLL cells. TAK-659 suppressed splenomegaly and tumor development in an LMP2A/Myc mouse model in nanomolar concentrations. In addition, TAK-659 also blocked metastasis of tumor cells into bone marrow. A phase Ib/II study of TAK-659 is underway in patients with relapsed or refractory acute myelogenous leukemia

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tyrosine-protein kinase SYK 21 Target ID: P43405 Gene ID: 6850.0 Gene Symbol: SYK Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/27839918	Inhibitor 8297		3.2 nM [IC50]

PubMed

Title	Date	PubMed
Syk inhibitors in clinical development for hematological malignancies.	2017 Jul 28	28754125

Sample Use Guides

In Vivo Use Guide

During the phase Ib dose escalation study, adult pts with R/R AML received oral TAK-659 daily at doses of 60, 100, 120, and 160 mg.

Route of Administration: Oral

Name

Type

Language

MIVAVOTINIB CITRATE

Official Name

English

3H-PYRROLO(3,4-C)PYRIDIN-3-ONE, 6-(((1R,2S)-2-AMINOCYCLOHEXYL)AMINO)-7-FLUORO-1,2-DIHYDRO-4-(1-METHYL-1H-PYRAZOL-4-YL)-, 2-HYDROXY-1,2,3-PROPANETRICARBOXYLATE (1:1)

Systematic Name

English

6-[[(1R,2S)-2-Aminocyclohexyl]amino]-7-fluoro-1,2-dihydro-4-(1-methyl-1H-pyrazol-4-yl)-3H-pyrrolo[3,4-c]pyridin-3-one, 2-hydroxypropane-1,2,3-tricarboxylate (1:1)

Systematic Name

English

6-(((1R,2S)-2-AMINOCYCLOHEXYL)AMINO)-7-FLUORO-4-(1-METHYL-1H-PYRAZOL-4-YL)-1,2-DIHYDRO-3H-PYRROLO(3,4-C)PYRIDIN-3-ONE MONOCITRATE

Systematic Name

English

TAK-659

Code

English

MIVAVOTINIB CITRATE [USAN]

Common Name

English

6-(((1R,2S)-2-AMINOCYCLOHEXYL)AMINO)-7-FLUORO-4-(1-METHYL-1H-PYRAZOL-4-YL)-1,2-DIHYDRO-3H-PYRROLO(3,4-C)PYRIDINE-3-ONE MONOCITRATE

Systematic Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

671718