CC-401 hydrochloride

Research use only, not for human use.

CC-401 hydrochloride is a potent, selective, ATP-competitive pan-JNK inhibitor with Ki of 25-50 nM.

CC-401 hydrochloride is a potent, selective, ATP-competitive pan-JNK inhibitor with Ki of 25-50 nM, displays >40-fold selectivity over other related kinases, including p38, ERK, IKK2, PK C, Lck, and ZAP70; decreases hepatic necrosis and apoptosis after orthotopic liver transplantation in vivo; blocks JNK signaling in the rat obstructed kidney and significantly inhibits renal fibrosis in terms of interstitial myofibroblast accumulation and collagen IV deposition, also significantly reduces tubular apoptosis in the obstructed kidney; sensitizes hypoxic colon cancer cells to DNA-damaging agents, potentiates the effect of bevacizumab and oxaliplatin in HT29-derived mouse xenografts.Blood CancervPhase 1 Discontinued(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. (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. 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.

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CC 401 hydrochloride | CC401 hydrochloride | CC401 HCl

MAPK/ERK Signaling

JNK

JNK

Cancer

Blood cancer

1438391-30-0

424.9265

C22H25ClN6O

>98% (HPLC)

10 mM in DMSO

C1CCN(CC1)CCOC2=CC=CC(=C2)C3=NNC4=C3C=C(C=C4)C5=NC=NN5.Cl

1H-Indazole, 3-[3-[2-(1-piperidinyl)ethoxy]phenyl]-5-(1H-1,2,4-triazol-5-yl)-, hydrochloride (1:1)

(-20℃)

With Ice Pack

≥ 2 years