TCH-165 is a small molecule modulator of proteasome assembly, which increases 20S levels and facilitates 20S-mediated protein degradation.

Product information

CAS Number: 1446350-60-2

Molecular Weight: 595.73

Formula: C39H37N3O3

Chemical Name: ethyl (4R,5R)-1-benzyl-5-[4-(benzylamino)phenyl]-2-(4-methoxyphenyl)-4-phenyl-4,5-dihydro-1H-imidazole-4-carboxylate

Smiles: COC1C=CC(=CC=1)C1=N[C@]([C@@H](C2C=CC(=CC=2)NCC2C=CC=CC=2)N1CC1C=CC=CC=1)(C(=O)OCC)C1C=CC=CC=1

InChiKey: XXDLWRCUPASJGY-AEGYFVCZSA-N

InChi: InChI=1S/C39H37N3O3/c1-3-45-38(43)39(33-17-11-6-12-18-33)36(31-19-23-34(24-20-31)40-27-29-13-7-4-8-14-29)42(28-30-15-9-5-10-16-30)37(41-39)32-21-25-35(44-2)26-22-32/h4-26,36,40H,3,27-28H2,1-2H3/t36-,39-/m1/s1

Technical Data

Appearance: Solid Power

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

Solubility: DMSO : 250 mg/mL (419.65 mM; Need ultrasonic).

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: ≥12 months 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:

TCH-165 (0.01-10 μM; 72 hours; RPMI8226 and U87MG cells) treatment inhibits cell growth of RPMI8226 and U87MG cells with IC50 of 1.6 μM and 2.4 μM, respectively. TCH-165 (0-10 μM; 24 hours; HEK293T cells) treatment enhances ODC degradation is blocked by BTZ indicated that this event is proteasome-mediated. TCH-165 enhances proteolytic degradation in a concentration-dependent manner. TCH-165 enhances the chymotrypsin-like (CT-L), trypsin-like (Tryp-L) and caspase-like (Casp-L) activities with EC50s of 4.2 μM, 3.2 μM and 4.7 μM, respectively. TCH-165 enhances 20S-mediated degradation of IDPs, α-syn, and tau in vitro, and does not induce the degradation of structured proteins such as GAPDH. TCH-165-treated cells display a decrease in the assembled 26S and an increase in the 20S proteasome. TCH-165 regulates the dynamic equilibrium between the 20S and 26S proteasome complexes, favoring 20S-mediated protein degradation.

References:

1. Njomen E, et al. Small Molecule Modulation of Proteasome Assembly. Biochemistry. 2018 Jul 17;57(28):4214-4224.

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