CC-401 Hydrochloride (CC401 HCl) is a second generation ATP-competitive anthrapyrazolone c-Jun N terminal kinase (JNK) inhibitor (Ki of 25 to 50 nM.)with potential antineoplastic activity.

JNK:25-50 nM (Ki)

CC-401与化疗化合物联合在结肠癌细胞系中展现出协同作用，尽管这种协同作用并非总是特异性与低氧有关。详细分析主要针对HT29和SW620（敏感）及HCT116（不敏感）细胞系。在HT29和SW620细胞中，CC-401治疗导致敏感细胞中的DNA损伤更为显著。

在体内，通过JNK抑制增强了bevacizumab、oxaliplatin及其联合使用在HT29衍生的小鼠异种移植瘤中的效果，其中CC-401存在时的肿瘤生长延迟更为显著。最终，将一个占优势的负向JNK1构建（但不是JNK2）稳定引入HT29细胞中，使其在低氧条件下对oxaliplatin的敏感度提高，这表明JNK亚型在细胞对化疗反应中有不同的输入。

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.