1. MAPK/ERK Pathway
  2. JNK

CC-401 hydrochloride (Synonyms: CC401 HCl)

Cat. No.: HY-13022 Purity: 99.45%
Handling Instructions

CC-401 hydrochloride is a potent inhibitor of all three forms of JNK with Ki of 25 to 50 nM.

For research use only. We do not sell to patients.

CC-401 hydrochloride Chemical Structure

CC-401 hydrochloride Chemical Structure

CAS No. : 1438391-30-0

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Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 198 In-stock
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Estimated Time of Arrival: December 31
5 mg USD 180 In-stock
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10 mg USD 324 In-stock
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Estimated Time of Arrival: December 31
50 mg USD 960 In-stock
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Other Forms of CC-401 hydrochloride:

    CC-401 hydrochloride purchased from MCE. Usage Cited in: Science. 2017 Dec 1;358(6367). pii: eaan4368.

    Kinobead western Blot readout for selected inhibitor:protein combinations.

    CC-401 hydrochloride purchased from MCE. Usage Cited in: Science. 2017 Dec 1;358(6367). pii: eaan4368.

    Immunoblot analysis in MV-4-11 cells and MOLM-13, FLT3-WT and FLT3-ITD transfected HEK293 cells, and Ba/F3 FLT3-ITD cells revealed FLT3 target engagement for Golvatinib and Cabozantinib.

    View All JNK Isoform Specific Products:

    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    CC-401 hydrochloride is a potent inhibitor of all three forms of JNK with Ki of 25 to 50 nM.

    IC50 & Target[1]

    JNK

    25-50 nM (Ki)

    In Vitro

    CC-401 has at least 40-fold selectivity for JNK compared with other related kinases, including p38, extracellular signal-regulated kinase (ERK), inhibitor of κB kinase (IKK2), protein kinase C, Lck, zeta-associated protein of 70 kDa (ZAP70). In cell-based assays, 1 to 5 μM CC-401 provides specific JNK inhibition. CC-401, a small molecule that is a specific inhibitor of all three JNK isoforms. CC-401 competitively binds the ATP binding site in JNK, resulting in inhibition of the phosphorylation of the N-terminal activation domain of the transcription factor c-Jun. The specificity of this inhibitor is tested in vitro using osmotic stress of the HK-2 human tubular epithelial cell line. CC-401 inhibits sorbitol-induced phosphorylation of c-Jun in a dosage-dependent manner. However, CC-401 does not prevent sorbitol-induced phosphorylation of JNK, p38, or ERK[1].

    In Vivo

    The staining of p-JNK is moderately induced in bevazicumab and Oxaliplatin treatments as compared to control, and in the CC-401-treated samples p-cJun content is significantly lower, consistent with effective JNK inhibition. DNA damage is modestly elevated in combined treatments with CC-401[2]. CC-401 treatment from days 7 to 24 slows the progression of proteinuria, which is significantly reduced compared to the no-treatment and vehicle groups at days 14 and 21. However, there is still an increase in the degree of proteinuria at day 21 in CC-401-treated rats compared to proteinuria at day 5. The vehicle and no-treatment groups developed renal impairment at day 24 as shown by an increase in serum creatinine. This is prevented by CC-401 treatment[3].

    Clinical Trial
    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 2.3533 mL 11.7666 mL 23.5333 mL
    5 mM 0.4707 mL 2.3533 mL 4.7067 mL
    10 mM 0.2353 mL 1.1767 mL 2.3533 mL
    Please refer to the solubility information to select the appropriate solvent.
    Cell Assay
    [1]

    CC-401 is prepared in citric acid (pH 5.5)[1].

    Human HK-2 proximal tubular epithelial cells are cultured in DMEM/F12 media supplemented with 10% FCS, 10 ng/mL EGF, and 10 μg/mL bovine pituitary extract. For Western blot studies, cells are seeded into six-well plates and allowed to adhere overnight, and medium is changed to DMEM/F12 supplemented with only 0.5% FCS for 24 h, by which time cells are confluent. CC-401 is prepared in citric acid (pH 5.5) and added to the confluent cells 1 h before the addition of 300 mM sorbitol, and cells are harvested 30 min later using urea-RIPA buffer. Three experiments are performed, each with two replicates per condition. For ELISA experiments, HK-2 cells are seeded into 24-well plates, allowed to adhere overnight, cultured in DMEM/F12 with 0.5% FCS for 24 h, and then incubated with CC-401 or vehicle for 60 min before stimulation with 1 μM Angiotensin II (AngII). Supernatants are harvested 48 h later and assayed for TGF-β1 content using a commercial ELISA kit. Three experiments are performed, each using six replicates per condition[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [2][3]

    CC-401 is prepared in saline (Mice)[2].
    CC-401 is prepared in sodium citrate (Rats)[3].

    Mice[2]
    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) are used. To generate tumors, HT29 cells (1×106 cells) are injected subcutaneously into the left flank of the mice. When the tumors reached approximately 200 mm3, mice are 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 receive 5 mg/kg of Bevacizumab by intraperitoneal injection every 3 days for 21 days. The Oxaliplatin treatment group is injected intraperitoneally with 5 mg/kg Oxaliplatin per week for 2 weeks. The CC-401 treatment group is injected intraperitoneally 25 mg/kg for every 3 days. The combination treatment groups receive 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 receive saline intraperitoneally. Tumor volume and body weight are measured every 3 days. Tumor volume is calculated. Tumor growth delay is calculated as the difference in the time for control and treated tumors to grow from 200 to 800 mm3. For tumor growth delay calculations, mice are continued to receive treatments till the tumor volume reached 800 mm3. For immunohistochemistry mice are sacrificed after treatments on day 9 for tumor processing and staining.
    Rats[3]
    Female WKY rats (180-220 g) are used. Groups of 9 or 10 rats are immunized by subcutaneous injection of 5 mg of sheep IgG in Freund's complete adjuvant followed 5 days later (termed day 0) by a tail vein injection of sheep anti-rat GBM serum. In this study, CC-401 (200 mg/kg/b.i.d. by oral gavage) or vehicle (sodium citrate) treatment is initiated in groups of 9 or 10 rats at 7 days after anti-GBM serum administration and continued twice daily thereafter until animals are killed at day 24. Additional groups of rats without treatment are killed at day 7 or day 24 after anti-GBM serum injection as controls. Animals are housed in metabolic cages for 22 hours to collect urine on days 5, 14, and 21. Blood is collected at the time of death. Analysis of serum creatinine and urinary protein are performed. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    424.93

    Formula

    C₂₂H₂₅ClN₆O

    CAS No.

    1438391-30-0

    SMILES

    C1(C2=CC=CC(OCCN3CCCCC3)=C2)=NNC4=C1C=C(C=C4)C5=NC=NN5.Cl

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    10 mM in DMSO

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

    Purity: 99.45%

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    Inquiry Information

    Product Name:
    CC-401 hydrochloride
    Cat. No.:
    HY-13022
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