BALIPODECT

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H17FN6O2
Molecular Weight	428.4185
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CN(N=C(C2=CC=NN2C3=CC=CC=C3)C1=O)C4=CC=C(C=C4F)N5C=CC=N5

InChI

InChIKey=KVHRYLNQDWXAGI-UHFFFAOYSA-N

InChI=1S/C23H17FN6O2/c1-32-21-15-29(19-9-8-17(14-18(19)24)28-13-5-11-25-28)27-22(23(21)31)20-10-12-26-30(20)16-6-3-2-4-7-16/h2-15H,1H3

HIDE SMILES / InChI

Molecular Formula	C23H17FN6O2
Molecular Weight	428.4185
Charge	0
Count

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

Description
Sources: https://huntingtonsdiseasenews.com/2016/11/08/investigational-drug-appears-improve-huntingtons-symptoms-mice/ | https://www.ncbi.nlm.nih.gov/pubmed/25384088
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/27811172

TAK-063 is a highly potent, selective, and orally active phosphodiesterase 10A (PDE10A) inhibitor with IC50 of 0.30 nM; >15000-fold selectivity over other PDEs. TAK-063 is currently being evaluated in clinical trials for the treatment of schizophrenia. Phosphodiesterase 10A (PDE10A) is a cAMP/cGMP phosphodiesterase highly expressed in medium spiny neurons (MSNs) in the striatum. TAK-063 represents a promising drug for the treatment of schizophrenia with potential for superior safety and tolerability profiles.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Phosphodiesterase 10A 12 Target ID: CHEMBL4409 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25384088 \| https://www.ncbi.nlm.nih.gov/pubmed/25815469	Inhibitor 8297		0.3 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Schizophrenia 298 Sources: https://clinicaltrials.gov/ct2/show/NCT02477020	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
245.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27572830	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:		TAK-063 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
5788.1 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27572830	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:		TAK-063 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
14.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27572830	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:		TAK-063 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
3.6% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29345044			TAK-063 plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	inhibitor 1767 substrate 1037	inhibitor 1852 substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 P-gp 1461 CYP2B6 810 CYP2C8 911 CYP3A4/5 278 CYP2C19 1478	P-gp 1537 BCRP 561 CYP3A4/5 85 CYP2C8 693 CYP2C19 991 CYP2B6 664 CYP1A2 1054	CYP3A4/5 124 CYP1A2 701 CYP2B6 547

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP1A2 1692	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/29345044/	likely
CYP2B6 1001	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/29345044/	likely
CYP2B6 1001	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/29345044/	likely	M-I 1
CYP3A4/5 335	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/29345044/	likely
CYP3A4/5 335	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/29345044/	likely	M-I 1
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29345044/	unlikely [IC50 >20 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29345044/	unlikely [IC50 >20 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29345044/	unlikely [IC50 >20 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29345044/	unlikely [IC50 >20 uM]
CYP3A4/5 335	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29345044/	unlikely [IC50 >20 uM]
CYP1A2 1692	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/29345044/	unlikely	M-I 1
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29345044/	yes [IC50 12 uM]
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29345044/	yes [IC50 7.13 uM]
CYP2C8 965	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29345044/	yes [IC50 8.4 uM]

Drug as victim

Target	Modality	Activity
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/29345044/	major
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/29345044/	major
CYP3A4/5 85	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/29345044/	major
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/29345044/	minor
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/29345044/	minor
BCRP 561	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/29345044/	no
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/29345044/	no
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/29345044/	yes
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/29345044/	yes

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P009D12	https://www.1pchem.com/search?query=1P009D12
AstaTech	40097	http://astatechinc.com/CPSResult.php?CRNO=40097
Axon MedChem	2399	https://www.axonmedchem.com/product/2399
BLD Pharm	BD630041	http://www.bldpharm.com/search/Search.html?keyword=BD630041
Chem Scene	CS-3551	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3551
ChemShuttle	157309	https://www.chemshuttle.com/catalogsearch/result/?q=157309
Excenen	EX-A568	http://www.excenen.com/searchresultlist.php?id=EX-A568
MedChem Express	HY-12472	https://www.medchemexpress.com/search.html?q=HY-12472&ft=&fa=&fp=
MolPort	MolPort-042-665-865	https://www.molport.com/shop/molecule-link/MolPort-042-665-865
Molnova	M10959	https://www.molnova.com/en/serch-list.html?keywords=M10959
MuseChem	I000951	https://www.musechem.com/product/I000951.html
Ryan Scientific	Dalbavancin_HCl	https://ryansci.com/products?q=Dalbavancin_HCl&list_q=&search_type=exact
Selleck Chemicals	S8459	http://www.selleckchem.com/search.html?searchDTO.searchParam=S8459
ShangHai Biochempartner	BCP001382	http://www.biochempartner.com/search_BCP001382
ShangHai Biochempartner	BCP14040	http://www.biochempartner.com/search_BCP14040
TargetMol	T1745	https://www.targetmol.com/search?keyword=T1745
eMolecules	50550848	https://orderbb.emolecules.com/search/#?query=50550848
mcule	MCULE-6938777299	https://mcule.com/MCULE-6938777299/

PubMed

Title	Date	PubMed
Discovery of 1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one (TAK-063), a highly potent, selective, and orally active phosphodiesterase 10A (PDE10A) inhibitor.	2014 Nov 26	25384088
Characterization of binding and inhibitory properties of TAK-063, a novel phosphodiesterase 10A inhibitor.	2015	25815469
TAK-063, a Novel Phosphodiesterase 10A Inhibitor, Protects from Striatal Neurodegeneration and Ameliorates Behavioral Deficits in the R6/2 Mouse Model of Huntington's Disease.	2017 Jan	27811172

Patents

Sample Use Guides

In Vivo Use Guide

TAK-063 20 (milligram) mg, tablets, orally, once daily for up to 6 weeks. Dose may be titrated down to 10 mg/day, if intolerable.

Route of Administration: Oral

In Vitro Use Guide

TAK-063 has shown high inhibitory activity and selectivity for human recombinant PDE10A2 in vitro; the half-maximal inhibitory concentration was 0.30 nM, and selectivity over other phosphodiesterases (PDEs) was more than 15000-fold. TAK-063 at 10 uM did not show more than 50% inhibition or stimulation of 91 enzymes or receptors except for PDEs.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 08:39:56 GMT 2023` Edited by `admin` on `Sat Dec 16 08:39:56 GMT 2023`
Record UNII	6650W303H0
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BALIPODECT

Official Name

English

1-(2-FLUORO-4-(1H-PYRAZOL-1-YL)PHENYL)-5-METHOXY- 3-(1-PHENYL-1H-PYRAZOL-5-YL)PYRIDAZIN-4(1H)-ONE

Systematic Name

English

TAK-063

Code

English

BALIPODECT [USAN]

Common Name

English

4(1H)-PYRIDAZINONE, 1-(2-FLUORO-4-(1H-PYRAZOL-1-YL)PHENYL)-5-METHOXY-3-(1-PHENYL-1H-PYRAZOL-5-YL)-

Systematic Name

English

Balipodect [WHO-DD]

Common Name

English

balipodect [INN]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

689219