| CUDC-101 is a potent HDAC, EGFR and HER2 inhibitor with IC50 values of 4.4, 2.4, and 15.7 nM, respectively. CUDC-101 has weak inhibition of protein kinases KDR, Src, Lyn, Lck, Abl-1, FGFR-2, Flt-3, and Ret with IC50 values ??840 nM. CUDC-101 significantly inhibits the growth of NSCLC cancer cell line HCC827, liver cancer cell line HepG2, pancreatic cancer cell line Capan1, and breast caner cell line MCF-7 with IC50 values of 600, 130, 800 and 550 nM, respectively, with higher potency than erlotinib, lapatinib, and combinations of vorinostat with either erlotinib or lapatinib.[1] In another in vitro assays, CUDC-101 significantly inhibits the growth of a broad range of cancer cell types, including lung, pancreas, liver, colon, breast, prostate, and head and neck.[2] In vivo, CUDC-101 (120 mg/kg) induces tumor regression in the HepG2 liver cancer model and is more efficacious than erlotinib at maximum tolerated dose. In the erlotinib-resistant A549 NSCLC xenograft model, CUDC-101 (120 mg/kg) shows potent inhibition of tumor growth with T/C % value of 35.9%. In the erlotinib-sensitive H358 NSCLC models, CUDC-101 (15, 30 and 60 mg/kg) also inhibits tumor growth in a dose-dependent manner. In addition, CUDC-101 (120 mg/kg) causes significant tumor regression in the lapatinib-resistant MDA-MB-468 breast cancer model and the EGFR-overexpressing CAL-27 head and neck squamous cell carcinoma (HNSCC) model.[1] |
