COTI-2

SKU: orb1302950

Description

COTI-2 is an orally bioavailable thiosemicarbazone compound that acts as a mutant p53 activator, exhibiting potential anticancer properties. It has demonstrated antitumor efficacy in both cellular assays and animal models, supporting its investigation in oncology research.

Research Area

Cell Biology

Key Properties

• CAS Number: 1039455-84-9
• MW: 366.48
• Purity: 99.55% (May vary between batches)
• Formula: C₁₉H₂₂N₆S
• SMILES: S=C(N\N=C1/CCCc2cccnc12)N1CCN(CC1)c1ccccn1
• Target: MDM-2/p53,Apoptosis,p53
• Solubility: DMSO:5 mg/mL (13.64 mM)

Bioactivity

• In Vivo:
  In the HT-29 human colorectal tumor xenografts, COTI-2 (10 mg/kg) markedly inhibits tumor growth. Except for reducing tumor volumes at specific times post-treatment, COTI-2 also increases the time required for tumors to reach specified volumes. In the SHP-77 SCLC xenograft model, COTI-2 (3 mg/kg) also markedly inhibits tumor growth. COTI-2 can reduce U87-MG tumor volumes at specific times post-treatment and lengthen the time required for U87-MG xenografts to grow in nude mice. Control tumors in mice treated with vehicle alone take only 5 days to reach an average volume of 828 mm3 while tumors in animals treated with COTI-2 take double that time (10 days) to reach a similar mean volume (857 mm3). Regardless of the route of administration, COTI-2 potently inhibits OVCAR-3 xenograft growth.
• In Vitro:
  COTI-2 (72 h) potently inhibits the proliferation rate of all the tested cell lines. In COLO-205, HCT-15, and SW620 cell lines, COTI-2 markedly inhibits tumor cell proliferation. Relatively low concentrations of COTI-2 are active against all human glioblastoma cell lines tested (U87-MG, SNB-19, SF-268, and SF-295). In SHP-77 cells, COTI-2 treatment with IC50 concentrations causes the induction of early apoptosis among 40 to 47% of total cells.
• Cell Research:
  COTI-2 is dissolved in 100% dimethyl sulfoxide stock solution and diluted in medium plus FBS such that final DMSO concentrations are 0.5 to 1.0% depending on the experiment.SHP-77 cells are cultured with various concentrations of COTI-2 for 48 h. Cells are then washed twice with 1× cold PBS and stained with Annexin V and 7AAD according to the manufacturer's instructions. Briefly, 5 μL of Annexin V and 7AAD are added to 1×105 cells and incubated for 15 min at room temperature in the dark. Then 400 μL of the 1× binding buffer (100 mM HEPES, pH 7.4, 140 mM NaCl, 2.5 mM CaCl2) is added to the cells. Finally, cells are analyzed using a flow cytometer.
• Animal Research:
  SHP-77 and HT-29 cells are injected in 50% matrigel into flanks of NCr-nu mice (2×106 cells per injection site) (n=5 mice per group). In the case of SHP-77 xenografts, treatment with COTI-2 begins prior to the appearance of palpable tumors. One day after injection of SHP-77 cells, animals receive 3 mg/kg of COTI-2 (once every two days, up to 38 days). Tumor sizes are estimated at 5, 10, 17, 24, and 38 days, by standard caliper measurements. In the case of HT-29 xenografts, the capacity of COTI-2 to suppress the growth of established tumors is assessed. HT-29 xenografts are allowed to grow to 200 mm3 before starting IP treatment with COTI-2 (10 mg/kg, 5 days a week for 7 weeks) or saline IP. Tumor growth is measured every 4 days by caliper measurement.

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

toxicity, TNBC, HNSCC, MDM-2/p53, orally, Inhibitor, low, p53, inhibit, anti-cancer, anti-proliferative, Apoptosis, COTI 2, COTI-2, COTI2

Compound Identifiers

PubChem CID

91810660