MIVAVOTINIB CITRATE

Investigational

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

Molecular Formula	C17H21FN6O
Molecular Weight	344.3866
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	C6H8O7
Molecular Weight	192.1235
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 22 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 8504		3.2 nM [IC50]

C_max

Value	Dose	Analyte	Population
93.86 ng/mL CLINICAL TRIAL https://clinicaltrials.gov/study/NCT03238651?term=tak-659&aggFilters=results:with&rank=1&tab=results	40 mg 1 times / day multiple, oral dose: 40 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MIVAVOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN
127.65 ng/mL CLINICAL TRIAL https://clinicaltrials.gov/study/NCT03238651?term=tak-659&aggFilters=results:with&rank=1&tab=results	60 mg 1 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MIVAVOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
214.5 ng/mL CLINICAL TRIAL https://clinicaltrials.gov/study/NCT03238651?term=tak-659&aggFilters=results:with&rank=1&tab=results	80 mg 1 times / day multiple, oral dose: 80 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MIVAVOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
216 ng/mL CLINICAL TRIAL https://clinicaltrials.gov/study/NCT03238651?term=tak-659&aggFilters=results:with&rank=1&tab=results	80 mg 1 times / day multiple, oral dose: 80 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MIVAVOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
297 ng/mL CLINICAL TRIAL https://clinicaltrials.gov/study/NCT03238651?term=tak-659&aggFilters=results:with&rank=1&tab=results	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MIVAVOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
121.18 ng/mL CLINICAL TRIAL https://clinicaltrials.gov/study/NCT03238651?term=tak-659&aggFilters=results:with&rank=1&tab=results	40 mg 1 times / day multiple, oral dose: 40 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MIVAVOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN
130.23 ng/mL CLINICAL TRIAL https://clinicaltrials.gov/study/NCT03238651?term=tak-659&aggFilters=results:with&rank=1&tab=results	60 mg 1 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MIVAVOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
308.29 ng/mL CLINICAL TRIAL https://clinicaltrials.gov/study/NCT03238651?term=tak-659&aggFilters=results:with&rank=1&tab=results	80 mg 1 times / day multiple, oral dose: 80 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MIVAVOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
339.42 ng/mL CLINICAL TRIAL https://clinicaltrials.gov/study/NCT03238651?term=tak-659&aggFilters=results:with&rank=1&tab=results	80 mg 1 times / day multiple, oral dose: 80 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MIVAVOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
329 ng/mL CLINICAL TRIAL https://clinicaltrials.gov/study/NCT03238651?term=tak-659&aggFilters=results:with&rank=1&tab=results	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MIVAVOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
115.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32327472/	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MIVAVOTINIB CITRATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
587.2534 ng × h/mL CLINICAL TRIAL https://clinicaltrials.gov/study/NCT03238651?term=tak-659&aggFilters=results:with&rank=1&tab=results	40 mg 1 times / day multiple, oral dose: 40 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MIVAVOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN
1207.6554 ng × h/mL CLINICAL TRIAL https://clinicaltrials.gov/study/NCT03238651?term=tak-659&aggFilters=results:with&rank=1&tab=results	60 mg 1 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MIVAVOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1742.7394 ng × h/mL CLINICAL TRIAL https://clinicaltrials.gov/study/NCT03238651?term=tak-659&aggFilters=results:with&rank=1&tab=results	80 mg 1 times / day multiple, oral dose: 80 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MIVAVOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1899.2508 ng × h/mL CLINICAL TRIAL https://clinicaltrials.gov/study/NCT03238651?term=tak-659&aggFilters=results:with&rank=1&tab=results	80 mg 1 times / day multiple, oral dose: 80 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MIVAVOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1828.4544 ng × h/mL CLINICAL TRIAL https://clinicaltrials.gov/study/NCT03238651?term=tak-659&aggFilters=results:with&rank=1&tab=results	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MIVAVOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
1114.2391 ng × h/mL CLINICAL TRIAL https://clinicaltrials.gov/study/NCT03238651?term=tak-659&aggFilters=results:with&rank=1&tab=results	40 mg 1 times / day multiple, oral dose: 40 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MIVAVOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN
2016.8 ng × h/mL CLINICAL TRIAL https://clinicaltrials.gov/study/NCT03238651?term=tak-659&aggFilters=results:with&rank=1&tab=results	60 mg 1 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MIVAVOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3502.3513 ng × h/mL CLINICAL TRIAL https://clinicaltrials.gov/study/NCT03238651?term=tak-659&aggFilters=results:with&rank=1&tab=results	80 mg 1 times / day multiple, oral dose: 80 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MIVAVOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3349.4133 ng × h/mL CLINICAL TRIAL https://clinicaltrials.gov/study/NCT03238651?term=tak-659&aggFilters=results:with&rank=1&tab=results	80 mg 1 times / day multiple, oral dose: 80 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MIVAVOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1357 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32327472/	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MIVAVOTINIB CITRATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
34 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/36309821/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		MIVAVOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
25.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32327472/	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MIVAVOTINIB CITRATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
55% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32327472/	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MIVAVOTINIB CITRATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

PubMed

Title	Date	PubMed
Syk inhibitors in clinical development for hematological malignancies.	2017-07-28	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

Substance Class	Chemical Created by `admin` on `Wed Apr 02 11:13:05 GMT 2025` Edited by `admin` on `Wed Apr 02 11:13:05 GMT 2025`
Record UNII	6ZJ8V3Q0H1
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

MIVAVOTINIB CITRATE

Official Name

English

MIVAVOTINIB CITRATE [USAN]

Preferred 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

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