COH000

SKU: orb1302002

Description

COH000 is an irreversible covalent inhibitor of the SUMO-activating enzyme, effectively blocking SUMOylation with an in vitro IC50 of approximately 0.2 µM. This compound is a valuable research tool for investigating SUMOylation's role in cellular processes such as stress response, cell cycle regulation, and DNA repair in both cellular and animal models.

Research Area

Protein Biochemistry

Key Properties

• CAS Number: 1534358-79-6
• MW: 419.47
• Purity: 99.23%
• Formula: C₂₅H₂₅NO₅
• SMILES: [H][C@]12O[C@@](C=C1)([C@@H](Cc1ccc(C)cc1)Nc1ccccc1)C(C(=O)OC)=C2C(=O)OC
• Target: E1/E2/E3 Enzyme
• Solubility: H2O:< 0.1 mg/mL (insoluble);DMSO:35.71 mg/mL (85.13 mM)

Bioactivity

• Target IC50:
  SUMO activating enzyme:0.2 μM (cell free)
• In Vivo:
  Once the tumor became palpable, the tumor-bearing Es1e/SCID mice were treated with COH000 or vehicle for 14 days. COH000 significantly inhibited tumor growth. In addition, COH000 significantly reduced SAE2 levels in tumor tissues.
• In Vitro:
  COH000 inhibited SUMOylation with an average IC50 of approximately 0.2 μM in vitro but did not inhibit ubiquitylation in a Ubc13-mediated poly-ubiquitylation assay tested under the same condition at concentrations up to 100 μM. COH000 treatment induced apoptosis in HCT-116 cells. The level of apoptosis was reduced when SAE2 was overexpressed by transfection and was increased when SAE2 was knocked down in HCT116 cells.
• Cell Research:
  Cell proliferation was measured using a CellTiter 96 AQueous One Solution Cell Proliferation Assay (MTS-based) after COH000 or its analog (54 or 55) treatment at the indicated concentrations and the time points. Briefly, cells were incubated with 20 mL of CellTiter 96 AQueous reagentafter the treatment and incubated at 37C until color development. Absorbance measurements were performed using a SpectraMax M5 reader. For assays measuring anti-proliferation effects, all values were normalized to the vehicle treatment. All values are represented graphically as mean ± standard deviation (STDEV) from three independent samples (n=3).
• Animal Research:
  Mice were housed in a controlled environment (12-h light/12-h dark cycle) with access to waterand fed a standard diet generally from 6 to 8 weeks of age. Body weight was measured weekly and food intake was monitored. For colorectal cancer xenograft with COH000 treatment, HCT116 cells were s.c. injected into a plasma esterase-deficient SCID mouse strain (Es1e/SCID), male, 8-10 weeks. When the tumors became palpable, COH000 was administered subcutaneously peritumoral injection once a day at a dose of 10 mg per kilogram of body weight. Mice in the control group received equal volumes of vehicle (5% DMSO, 30% solutol in PBS). Tumor volume was measured until the endpoint was reached. Mice were euthanized using CO2 inhalation and tumors were excised.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Ubiquitin-activating Enzyme E1, Ubiquitin ligase, Ubiquitin conjugating enzyme, Ubiquitin activating enzyme, Inhibitor, inhibit, E1 activating enzyme, E1/E2/E3 Enzyme, E1 Enzyme, E1Enzyme, E2 conjugating enzyme, E2 Enzyme, E3 ligating enzyme, E3Enzyme, E2Enzyme, E3 Enzyme, COH 000, COH000, COH-000

Compound Identifiers

PubChem CID

60156415