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

Structure Search

SMILES

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

Description
Sources: DOI: 10.1158/1535-7163 Retrived from | http://mct.aacrjournals.org/content/14/12_Supplement_2/A164

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 Target ID: P22314 Gene ID: 7317.0 Gene Symbol: UBA1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/29334375	Inhibitor 8504		1.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Advanced malignant solid tumors 6 Sources: https://clinicaltrials.gov/ct2/show/NCT02045095	Primary		Phase I 438	Unknown Approved Use Unknown

AUC

Value	Dose	Analyte	Population
752.152 ng × h/mL EXPERIMENT https://clinicaltrials.gov/ct2/show/results/NCT02045095	12 mg 2 times / week multiple, intravenous dose: 12 mg route of administration: Intravenous experiment type: MULTIPLE co-administered:	TAK-243 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
179.726 ng × h/mL EXPERIMENT https://clinicaltrials.gov/ct2/show/results/NCT02045095	4 mg 2 times / week multiple, intravenous dose: 4 mg route of administration: Intravenous experiment type: MULTIPLE co-administered:	TAK-243 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
509.785 ng × h/mL EXPERIMENT https://clinicaltrials.gov/ct2/show/results/NCT02045095	8 mg 2 times / week multiple, intravenous dose: 8 mg route of administration: Intravenous experiment type: MULTIPLE co-administered:	TAK-243 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
864.533 ng × h/mL EXPERIMENT https://clinicaltrials.gov/ct2/show/results/NCT02045095	18 mg 2 times / week multiple, intravenous dose: 18 mg route of administration: Intravenous experiment type: MULTIPLE co-administered:	TAK-243 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
27.446 h EXPERIMENT https://clinicaltrials.gov/ct2/show/results/NCT02045095	12 mg 2 times / week multiple, intravenous dose: 12 mg route of administration: Intravenous experiment type: MULTIPLE co-administered:	TAK-243 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
5.572 h EXPERIMENT https://clinicaltrials.gov/ct2/show/results/NCT02045095	4 mg 2 times / week multiple, intravenous dose: 4 mg route of administration: Intravenous experiment type: MULTIPLE co-administered:	TAK-243 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
15.212 h EXPERIMENT https://clinicaltrials.gov/ct2/show/results/NCT02045095	8 mg 2 times / week multiple, intravenous dose: 8 mg route of administration: Intravenous experiment type: MULTIPLE co-administered:	TAK-243 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
9.873 h EXPERIMENT https://clinicaltrials.gov/ct2/show/results/NCT02045095	18 mg 2 times / week multiple, intravenous dose: 18 mg route of administration: Intravenous experiment type: MULTIPLE co-administered:	TAK-243 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
18 mg 2 times / week multiple, intravenous Highest studied dose Dose: 18 mg, 2 times / week Route: intravenous Route: multiple Dose: 18 mg, 2 times / week Sources: https://clinicaltrials.gov/ct2/show/results/NCT02045095	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://clinicaltrials.gov/ct2/show/results/NCT02045095	Other AEs: Pyrexia, Dyspnoea... Other AEs: Pyrexia (1 pt) Dyspnoea (2 patients) Hypertension (1 pt) Dyspnoea exertional (1 pt) Sources: https://clinicaltrials.gov/ct2/show/results/NCT02045095

AEs

AE	Significance	Dose	Population
Dyspnoea exertional	1 pt	18 mg 2 times / week multiple, intravenous Highest studied dose Dose: 18 mg, 2 times / week Route: intravenous Route: multiple Dose: 18 mg, 2 times / week Sources: https://clinicaltrials.gov/ct2/show/results/NCT02045095	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://clinicaltrials.gov/ct2/show/results/NCT02045095
Hypertension	1 pt	18 mg 2 times / week multiple, intravenous Highest studied dose Dose: 18 mg, 2 times / week Route: intravenous Route: multiple Dose: 18 mg, 2 times / week Sources: https://clinicaltrials.gov/ct2/show/results/NCT02045095	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://clinicaltrials.gov/ct2/show/results/NCT02045095
Pyrexia	1 pt	18 mg 2 times / week multiple, intravenous Highest studied dose Dose: 18 mg, 2 times / week Route: intravenous Route: multiple Dose: 18 mg, 2 times / week Sources: https://clinicaltrials.gov/ct2/show/results/NCT02045095	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://clinicaltrials.gov/ct2/show/results/NCT02045095
Dyspnoea	2 patients	18 mg 2 times / week multiple, intravenous Highest studied dose Dose: 18 mg, 2 times / week Route: intravenous Route: multiple Dose: 18 mg, 2 times / week Sources: https://clinicaltrials.gov/ct2/show/results/NCT02045095	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://clinicaltrials.gov/ct2/show/results/NCT02045095

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

Name

Type

Language

TAK-243

Common Name

English

MLN-7243

Preferred Name

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

((1R,2R,3S,4R)-2,3-DIHYDROXY-4-((2-(3-(TRIFLUOROMETHYLSULFANYL)PHENYL)PYRAZOLO(1,5-A)PYRIMIDIN-7-YL)AMINO)CYCLOPENTYL)METHYL SULFAMATE

Systematic Name

English

TAK 243 [WHO-DD]

Common Name

English

Code System Code Type Description

CAS

1450833-55-2