CC-401 Hydrochloride

SKU: orb1301448

Description

CC-401 Hydrochloride

Research Area

Signal Transduction

Key Properties

• CAS Number: 1438391-30-0
• MW: 424.93
• Purity: ≥95%
• Formula: C₂₂H₂₅ClN₆O
• SMILES: Cl.C(CN1CCCCC1)Oc1cccc(c1)-c1n[nH]c2ccc(cc12)-c1ncn[nH]1
• Target: JNK
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:4 mg/mL (9.41 mM);DMSO:250 mg/mL (588.33 mM)

Bioactivity

• Target IC50:
  JNK:25-50 nM (Ki)
• In Vivo:
  In vivo, potentiation of bevacizumab, oxaliplatin, and the combination by JNK inhibition was confirmed in HT29-derived mouse xenografts, in which tumor growth delay was greater in the presence of CC-401. Finally, stable introduction of a dominant negative JNK1, but not JNK2, construct into HT29 cells rendered them more sensitive to oxaliplatin under hypoxia, suggesting differing input of JNK isoforms in cellular responses to chemotherapy.
• In Vitro:
  CC-401 in combination with chemotherapy demonstrates synergism in colon cancer cell lines, although synergy is not always hypoxia specific. A more detailed analysis focused on HT29 and SW620 (responsive), and HCT116 (nonresponsive) lines. In HT29 and SW620 cells, CC-401 treatment results in greater DNA damage in the sensitive cells.
• Animal Research:
  To assess the efficacy of JNK signaling inhibition by CC-401 in anti-angiogenic and oxaliplatin combination therapy in a mouse xenograft model, adult (8-10 weeks of age) female severe combined immunodeficient mice (C.B.17 SCID) were used. To generate tumors, HT29 cells (1 × 10^6 cells) were injected subcutaneously into the left flank of the mice. When the tumors reached approximately 200 mm^3, mice were divided into eight groups (eight mice per group) for treatment with bevacizumab , oxaliplatin, CC401, and the appropriate combinations of bevacizumab, oxaliplatin and CC-401. Mice in the bevacizumab treatment group received 5 mg/kg of bevacizumab by intraperitoneal injection every 3 days for 21 days. The oxaliplatin treatment group was injected intraperitoneally with 5 mg/kg oxaliplatin per week for 2 weeks. The CC-401 treatment group was injected intraperitoneally 25 mg/kg for every 3 days. The combination treatment groups received bevacizumab (every 3 days, 5 mg/kg), oxaliplatin (weekly for 2 weeks, 5 mg/kg), and CC-401 (every 3 days, 25 mg/kg). The control group received saline intraperitoneally. Tumor volume and body weight were measured every 3 days. Tumor volume was calculated using the formula V = AB^2/2, where A is the largest diameter and B is the smallest diameter. Tumor growth delay was calculated as the difference in the time for control and treated tumors to grow from 200 to 800 mm^3. For tumor growth delay calculations, mice were continued to receive treatments till the tumor volume reached 800 mm^3. For immunohistochemistry mice were sacrificed after treatments on day 9 for tumor processing and staining.

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

Inhibitor, inhibit, JNK, CC401, CC-401, CC401 HCl, CC401 Hydrochloride, CC-401 Hydrochloride, CC 401, CC 401 Hydrochloride

Compound Identifiers

PubChem CID

66576998