COH29

SKU: orb1304480

Description

COH29 is an orally bioavailable thiazole derivative that acts as a ribonucleotide reductase (RNR) inhibitor, targeting the hRRM2 subunit to deplete dNTP pools and impair DNA synthesis. It has demonstrated antineoplastic activity in vitro and in vivo, showing potential in cancer research, particularly in studies involving DNA replication stress and PARP1 inhibition.

Research Area

Cell Biology, Molecular Biology

Key Properties

• CAS Number: 1190932-38-7
• MW: 420.44
• Purity: 98.92% (May vary between batches)
• Formula: C₂₂H₁₆N₂O₅S
• SMILES: Oc1ccc(cc1O)C(=O)Nc1nc(c(s1)-c1ccccc1)-c1ccc(O)c(O)c1
• Target: DNA/RNA Synthesis
• Solubility: DMSO:50 mg/mL (118.92 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.76 mM)

Bioactivity

• Target IC50:
  RNR:16 μM.
• In Vivo:
  COH29 (50/100 mg/kg, b.i.d., p.o.)results in a dose-dependent inhibition of MOLT-4 tumor xenograft growth, which is pronounced by Day 12 of treatment. In mice bearing TOV11D xenografts, 7 days of treatment with COH29 (200/300/400 mg/kg/day) results in a dose-dependent inhibition of tumor xenograft growth. Compared with the control group, tumor growth is significantly inhibited .
• In Vitro:
  COH29 overcome gemcitabine and hydroxyurea resistance in Y cells. It potently inhibits proliferation of most cell lines in the NCI 60 human Y panel, most especially leukemia and ovarian Y, but exerts little effect on normal fibroblasts or endothelial cells. NMR, site-directed mutagenesis, and surface plasmon resonance biosensor studies confirm COH29 binding to the proposed ligand-binding pocket and offer evidence for assembly blockade of the RRM1-RRM2 quaternary structure.
• Cell Research:
  Cells is seeded into 96-well plates in 100 μL of complete medium at 2000 to 5000 cells per well, depending on the cell line's growth rate. After overnight incubation, test compound is added to each well at various concentrations in 50 μL of culture medium. After a further incubation for 96 hours at 37°C, fluorescein diacetate (final concentration: 10 mg/mL) and eosin Y [final concentration: 0.1% (w/v)] is added to each well, and the cells is incubated for an additional 20 minutes at 37°C. Cytotoxicity is assessed by Digital Imaging Microscopy System detection Viability is assessed using MTS [(3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium)] as previously described.

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

ribonucleotide, RNA Synthesis, RNR, RNR Inhibitor COH 29, RNR Inhibitor COH29, RNR Inhibitor COH-29, RNR( KB cell), RNASynthesis, subunit, COH 29, COH29, COH-29, DNA/RNA Synthesis, DNA Synthesis, DNASynthesis

Compound Identifiers

PubChem CID

44253415