N. 2 mg BID effectively suppressed ERK1 / 2 phosphorylation and Ki67 in tumor biopsies. Antikrebsaktivit t PD0325901 was CUDC-101 evaluated in 27 evaluable patients. Two partial responses were observed in melanoma patients, w While 8 patients had stable disease lasts 3 7 months. The Phase I study was extended and clinical activity Was t was by three partial responses in patients with melanoma and 24 F Lle documented stable disease in 66 patients. However PD0325901 was a severe toxicity t As IC 1040, including normal blurred vision and acute Neurotoxizit Linked t Patients, the drug more than 15 mg twice. The clinical development of this drug was discontinued in 2008. Benzimidazole AZD6244 AZD6244 is a potent inhibitor of other second generation MEK1/MEK2.
AZD6244 selectively inhibits purified active MEK1 and GSK256066 MEK2 with an IC50 of 14 nM by a mechanism not wettbewerbsf compatibility available with ATP. In cellular Ren assays basic compound inhibits growth factor stimulated the phosphorylation of ERK1 / 2 with IC50 concentrations of 40 nm, and exerts anti-proliferative effects on tumor cell lines by RAS or BRAF induced mutations. AZD6244 is a potent dose-Antitumoraktivit Shown t Ngig on a panel of mouse xenograft models of colon, pancreas, liver, skin and lung cancer. The inhibition of tumor growth was found tocorrelate reduced phospho ERK1 / 2 levels in tumors. Based on the promise of pre clinical activity T AZD6244 was well advanced in clinical development. A Phase I study was conducted to evaluate the safety, pharmacokinetics and pharmacodynamics of AZD6244 in 57 patients with advanced cancer.
The results of this study showed that 50% of the maximum tolerated dose was well tolerated, with rash being the h Most frequent toxicity t and dose limitation. Most other adverse events were grade 1 or 2 In particular, 7 patients developed transient and reversible changes Sehst Observed adverse reactions with PD0325901. A significant reduction in ERK1 / 2 phosphorylation was observed in tumor biopsies. Nine patients had stable disease for at least 5 months. Preferences INDICATIVE results from four randomized Phase II AZD6244 previously reported. In the first study, AZD6244 was compared with the alkylating agent temozolomide in patients with advanced melanoma. The antitumor activity of t Of AZD6244 was observed, but there was no significant difference in progression-free survival between the two treatment groups.
A second study compared the efficacy of AZD6244 with antimetabolite pemetrexed as second or third non-small cell lung cancer patients. Again, the study showed evidence Antitumoraktivit t monotherapy, but not to a difference in the primary Ren show endpoint of progression of the disease. In a third study, AZD6244 was with capecitabine in patients with metastatic colorectal cancer, the ne no Pl Prior irinotecan and / or oxaliplatin were compared. Similar no difference between the two treatments in the number of patients has been observed with the progression of the disease. After all, were the results of a phase II study of AZD6244 in patients with advanced or metastatic hepatocellular Ren carcinoma was reported. The study was stopped early due to lack of radiog
Related posts:
- DMXAA ASA404 are currently used in clinical trials in patients with HCC
- Nutlin-3 Cancer of 19 patients on therapy.
- Sodium Danshensu considerable variability in the patients’ clinical characteristics
- Commercially insured patients with lung cancer when compared with a matched control group
- Clofarabine Clolar showed that patients with residual platelet reactivity