CC-401

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

CC-401 (JNK-401) 是一种有效、选择性、ATP 竞争性泛 JNK 抑制剂，Ki 为 25-50 nM。

CC-401 (JNK-401) is a potent, selective, ATP-competitive pan-JNK inhibitor with Ki of 25-50 nM, displays >40-fold selectivity over other related kinases; blocks JNK signaling and renal fibrosis in a rat obstructed kidney model, decrease hepatic necrosis and apoptosis after orthotopic liver transplantation and prevent acute renal failure following ischemia/reperfusion associated with renal transplantation in rats.Blood Cancer Phase 1 Discontinued.

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.

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.

CC401 | JNK-401

MAPK/ERK Signaling

JNK

JNK

Cancer

Blood cancer

395104-30-0

388.5

C22H24N6O

>98% (HPLC)

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

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

(-20℃)

With Ice Pack

≥ 2 years