CC-401 dihydrochloride 

CC-401 dihydrochloride is a potent inhibitor of all three forms of JNK with K_i of 25 to 50 nM^[1].

Ki: 25 to 50 nM (JNK)^[1].

CC-401 dihydrochloride 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 dihydrochloride provides specific JNK inhibition. CC-401 dihydrochloride, a small molecule that is a specific inhibitor of all three JNK isoforms. CC-401 dihydrochloride 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 dihydrochloride inhibits sorbitol-induced phosphorylation of c-Jun in a dosage-dependent manner. However, CC-401 dihydrochloride does not prevent sorbitol-induced phosphorylation of JNK, p38, or ERK^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

461.39

C₂₂H₂₆Cl₂N₆O

2319601-04-0

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

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Vasilevskaya IA, et al. Inhibition of JNK Sensitizes Hypoxic Colon Cancer Cells to DNA-Damaging Agents. Clin Cancer Res. 2015 Sep 15;21(18):4143-52.  [Content Brief]

  [2]. Ma FY, et al. Blockade of the c-Jun amino terminal kinase prevents crescent formation and halts established anti-GBM glomerulonephritis in the rat. Lab Invest. 2009 Apr;89(4):470-84.  [Content Brief]

  [3]. Ma FY, et al. A pathogenic role for c-Jun amino-terminal kinase signaling in renal fibrosis and tubular cell apoptosis. J Am Soc Nephrol. 2007 Feb;18(2):472-84.  [Content Brief]