TAK-243 (MLN7243), Ubiquitin Activating Enzyme (UAE) Inhibitor

TAK-243 (MLN7243) is a potent, selective and cell permeable small molecule inhibitor of the ubiquitin activating enzyme (UAE) at nM range. The ubiquitin-activating enzymes, found more active in cancer cells than in normal healthy cells, catalyze the first step in ubiquitination reaction, targeting a protein for degradation via proteasome. TAK-243 treatment caused depletion of cellular ubiquitin conjugates, resulting in disruption of signaling events, induction of proteotoxic stress, and impairment of cell cycle progression and DNA damage repair pathways. TAK-243 treatment caused death of cancer cells and, in primary human xenograft studies, demonstrated antitumor activity at tolerated doses. Due to its specificity and potency, TAK-243 allows for interrogation of ubiquitin biology and for assessment of UAE inhibition as a new approach for cancer treatment. TAK-243 is now in phase I clinical trials for adult patients with advanced solid tumors.

Product information

CAS Number: 1450833-55-2

Molecular Weight: 519.52

Formula: C19H20F3N5O5S2

Chemical Name: ((1R,2R,3S,4R)-2,3-dihydroxy-4-(2-(3-(trifluoromethylthio)phenyl)pyrazolo[1,5-a]pyrimidin-7-ylamino)cyclopentyl)methyl sulfamate

Smiles: NS(=O)(=O)OC[C@H]1C[C@@H](NC2=CC=NC3=CC(=NN32)C2=CC(=CC=C2)SC(F)(F)F)[C@H](O)[C@@H]1O

InChiKey: KJDAGXLMHXUAGV-DGWLBADLSA-N

InChi: 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

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO up to 100 mM

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

TAK-243 was suggested to be used at 1-10 µM final concentration in vitro and in cellular assays.

In Vivo:

TAK-243 was administered intravenously at 12.5-25 mg/Kg to a panel of human-patient-derived and cell-line-derived xenograft (PDX and CDX, respectively) tumor models on a twice-per-week schedule.

References:

1. Hyer ML, et al. A small-molecule inhibitor of the ubiquitin activating enzyme for cancer treatment. (2018) Nat Med. In press.

Products are for research use only. Not for human use.