TAK-715

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H21N3OS
Molecular Weight	399.508
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCC1=NC(=C(S1)C2=CC(NC(=O)C3=CC=CC=C3)=NC=C2)C4=CC=CC(C)=C4

InChI

InChIKey=HEKAIDKUDLCBRU-UHFFFAOYSA-N

InChI=1S/C24H21N3OS/c1-3-21-27-22(18-11-7-8-16(2)14-18)23(29-21)19-12-13-25-20(15-19)26-24(28)17-9-5-4-6-10-17/h4-15H,3H2,1-2H3,(H,25,26,28)

HIDE SMILES / InChI

Molecular Formula	C24H21N3OS
Molecular Weight	399.508
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/16162000
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/17714020

TAK 715 is an orally bioavailable drug, which was developed by Takeda as Anti-inflammatory and anti-rheumatoid arthritis agent. This drug was in phase II of clinical trials, but that study was discontinued. TAK 715 is an inhibitor of p38 MAPK alpha and is inhibitor of Wnt-3a-stimulated β-catenin signaling.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
MAP kinase p38 alpha 35 Target ID: CHEMBL260 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16162000	Inhibitor 8297
MAP kinase p38 alpha 35 Target ID: CHEMBL260 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16162000	Inhibitor 8297	7.1 nM [IC50]
Wnt signaling pathway 13 Target ID: map04310 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21513885	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Rheumatoid arthritis 316 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16162000	Primary		Phase II 1132	Unknown Approved Use Unknown
Rheumatoid arthritis 316 Sources: https://clinicaltrials.gov/ct2/show/NCT00760864	Primary		Phase II 1132	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2E1 882 CYP2B6 810 P-gp 1461 CYP2C8 911 CYP1A1 110 CYP1A2 1524 CYP2C19 1478 CYP2A6 707

Drug as perpetrator

Target	Modality	Activity
CYP1A1 218	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16162000/	no
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16162000/	no
CYP2A6 739	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16162000/	no
CYP2B6 1001	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16162000/	no
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16162000/	no
CYP2C8 965	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16162000/	no
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16162000/	no
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16162000/	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16162000/ \| https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363677378	yes [IC50 2.6837 uM]
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=174006984	yes [IC50 20.931 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16162000/ \| https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=363677378	yes [IC50 7.5637 uM]

PubMed

Title	Date	PubMed
X-ray structure of p38α bound to TAK-715: comparison with three classic inhibitors.	2012 Aug	22868770
Tandem mass spectrometry study of p38α kinase inhibitors and related substances.	2013 Jun	23722963

Patents

Sample Use Guides

In Vivo Use Guide

TAK-715 25 mg, 50 mg and 100 mg tablets, orally, twice daily and methotrexate stable dose for up to 6 weeks.

Route of Administration: Oral

In Vitro Use Guide

It was synthesized a novel compound and evaluated it inhibition of p38 MAP kinase, lipopolysaccharide (LPS)-stimulated release of tumor necrosis factor-alpha (TNF-alpha) from human monocytic THP-1 cells in vitro. It was discovered, that TAK-715 exhibited potent inhibitory activity in these assays (inhibition of p38alpha, IC50 = 7.1 nM; LPS-stimulated release of TNF-alpha from THP-1, IC50 = 48 nM) and no inhibitory activity for major CYPs, including CYP3A4.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 17:15:24 UTC 2023` Edited by `admin` on `Fri Dec 15 17:15:24 UTC 2023`
Record UNII	WE92U03C5Z
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TAK-715

Common Name

English

BENZAMIDE, N-(4-(2-ETHYL-4-(3-METHYLPHENYL)-5-THIAZOLYL)-2-PYRIDINYL)-

Systematic Name

English

TAK 715

Code

English

Code System Code Type Description

PUBCHEM

9952773