TAK-243

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H20F3N5O5S2
Molecular Weight	519.518
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

NS(=O)(=O)OC[C@H]1C[C@@H](NC2=CC=NC3=CC(=NN23)C4=CC(SC(F)(F)F)=CC=C4)[C@H](O)[C@@H]1O

InChI

InChIKey=KJDAGXLMHXUAGV-DGWLBADLSA-N

InChI=1S/C19H20F3N5O5S2/c20-19(21,22)33-12-3-1-2-10(6-12)13-8-16-24-5-4-15(27(16)26-13)25-14-7-11(17(28)18(14)29)9-32-34(23,30)31/h1-6,8,11,14,17-18,25,28-29H,7,9H2,(H2,23,30,31)/t11-,14-,17-,18+/m1/s1

HIDE SMILES / InChI

Molecular Formula	C19H20F3N5O5S2
Molecular Weight	519.518
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

TAK-243 (MLN7243) is a small molecule inhibitor of ubiquitin-activating enzyme (UAE), with potential antineoplastic activity, which was developed by Takeda Oncology, Millennium. MLN7243 binds to and inhibits UAE, which prevents both protein ubiquitination and subsequent protein degradation by the proteasome. This inhibits tumor cell proliferation and survival. UAE, also called ubiquitin E1 enzyme (UBA1; E1), is more active in cancer cells than in normal, healthy cells. Currently, TAK-243 is in phase I clinical trial evaluating safety, tolerability, pharmacokinetics, pharmacodynamics against advanced malignant solid tumors phase.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Ubiquitin-like modifier-activating enzyme 1 2	Inhibitor 8,297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Advanced malignant solid tumors 6	Primary		Phase I 428	Unknown

AUC

Value	Dose	Analyte	Population
179.726 ng × h/mL	4 mg 2 times / week multiple, intravenous	TAK-243 plasma	Homo sapiens
509.785 ng × h/mL	8 mg 2 times / week multiple, intravenous	TAK-243 plasma	Homo sapiens
752.152 ng × h/mL	12 mg 2 times / week multiple, intravenous	TAK-243 plasma	Homo sapiens
864.533 ng × h/mL	18 mg 2 times / week multiple, intravenous	TAK-243 plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
5.572 h	4 mg 2 times / week multiple, intravenous	TAK-243 plasma	Homo sapiens
15.212 h	8 mg 2 times / week multiple, intravenous	TAK-243 plasma	Homo sapiens
27.446 h	12 mg 2 times / week multiple, intravenous	TAK-243 plasma	Homo sapiens
9.873 h	18 mg 2 times / week multiple, intravenous	TAK-243 plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
18 mg 2 times / week multiple, intravenous Highest studied dose	unhealthy n = 8	Other AEs: Pyrexia, Hypertension...

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AEs

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AE	Significance	Dose	Population
Dyspnoea exertional	1 pt	18 mg 2 times / week multiple, intravenous Highest studied dose	unhealthy n = 8
Hypertension	1 pt	18 mg 2 times / week multiple, intravenous Highest studied dose	unhealthy n = 8
Pyrexia	1 pt	18 mg 2 times / week multiple, intravenous Highest studied dose	unhealthy n = 8
Dyspnoea	2 patients	18 mg 2 times / week multiple, intravenous Highest studied dose	unhealthy n = 8

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Patents

Patents

Sample Use Guides

In Vivo Use Guide

Dose escalation stage: Schedule A: IV infusion on days 1, 4, 8, 11 for a 21-day treatment cycle Schedule B: IV infusion on days 1, 8, 15 for a 28-day treatment cycle Dose expansion stage: MLN7243 will be administered following schedule A (twice-weekly, 21-day dosing) and/or B (once-weekly, 28-day dosing)

Route of Administration: Intravenous

In Vitro Use Guide

Unknown

Substance Class	Chemical
Record UNII	V9GGV0YCDI
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

TAK-243

Common Name

English

MLN-7243

Code

English

UAE INHIBITOR MLN7243

Common Name

English

SULFAMIC ACID, ((1R,2R,3S,4R)-2,3-DIHYDROXY-4-((2-(3-((TRIFLUOROMETHYL)THIO)PHENYL)PYRAZOLO(1,5-A)PYRIMIDIN-7-YL)AMINO)CYCLOPENTYL)METHYL ESTER

Systematic Name

English

MLN7243

Code

English

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Code System

Code

Type

Description

CAS

1450833-55-2

PRIMARY

NCI_THESAURUS

C113788

PRIMARY

FDA UNII

V9GGV0YCDI

PRIMARY

PUBCHEM

71715374

PRIMARY

DRUG BANK

DB15013

PRIMARY

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Related Record

Type

Details


					V9GGV0YCDI

TAK-243

ACTIVE MOIETY

Comments:

Official Title: An Open-Label, Phase 1b, Multi-Arm Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of Investigational Treatments in Combination With Standard of Care Immune Checkpoint Inhibitors in Patients With Advanced Melanoma Purpose: The purpose of this study is to determine the initial safety profile of the combination treatments (immune checkpoint inhibitors (nivolumab, ipilimumab) with investigational drugs (TAK-580, TAK-202 (plozalizumab), vedolizumab)) in the 3 arms when administered to participants with advanced melanoma.


					V9GGV0YCDI

TAK-243

ACTIVE MOIETY

Comments:

Originator: Biogen Idec, Sunesis Pharmaceuticals; Developer: Takeda Oncology; Class: Anti-neoplastic; Mechanism of Action: Raf kinase inhibitor; Orphan Drug Status: No; On Fast track: No; New Molecular Entity: Yes; Highest Development Phases: Phase I for Malignant melanoma, Solid tumours; Most Recent Events: 16 Jul 2016 No recent reports of development identified for phase-I development in Solid-tumours(Second-line therapy or greater) in United Kingdom (PO, Tablet), 16 Jul 2016 No recent reports of development identified for phase-I development in Solid-tumours(Second-line therapy or greater) in USA (PO, Tablet), 01 May 2016 Phase-I clinical trials in Malignant melanoma (Combination therapy, Inoperable/Unresectable, Late-stage disease) in USA (PO) (NCT02723006)


					V9GGV0YCDI

TAK-243

ACTIVE MOIETY

Comments:

A UAE inhibitor potentially for the treatment of solid tumors. TAK-243, also known as MLN7243 and AOB87172, is a small molecule inhibitor of ubiquitin-activating enzyme (UAE), with potential antineoplastic activity. UAE inhibitor MLN7243 binds to and inhibits UAE, which prevents both protein ubiquitination and subsequent protein degradation by the proteasome. This results in an excess of proteins in the cells and may lead to endoplasmic reticulum (ER) stress-mediated apoptosis. This inhibits tumor cell proliferation and survival. UAE, also called ubiquitin E1 enzyme (UBA1, E1), is more active in cancer cells than in normal, healthy cells.


					V9GGV0YCDI

TAK-243

ACTIVE MOIETY

Comments:

Drug: TAK 243(Primary); Indication: Solid tumours; Focus: Adverse reactions; Sponsor: Takeda Oncology; Most Recent Event: 16 Feb 2014 New trial record

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SMILES

InChI

Originator

Approval Year

Targets

Conditions

AUC

T1/2

Doses

AEs

Patents

Sample Use Guides

T_1/2