Yp proteins. PLX4032 is said to have fewer side effects listed off sorafenib, it remains a liquid Surface of some controversy. PLX4032 inhibits ERK phosphorylation and because proliferation of cancer cell lines RAF mutations port B, but not the cells expressing DAPT the wild-type protein. Also inhibited the development of melanoma xenograft PLX4032 containing mutant RAF B demonstrated tumor regression and leased Ngerte delay Delay of tumor growth after the end of the dosage of medication. The clinical activity of PLX4032 was in a phase I study of 16 patients with melanoma V600EB RAF administration of the drug twice per day harboring gr Than or equal to 240 mg evaluated. The results showed that PLX4032 was good, even at very high doses is well tolerated.
Expansion in a Phase I, which contain patient that mutation positive, 15 of 31 KW 2449 had tumor regression greater than 50%, and 18 patients responded partially showing gr He than 30% tumor regression. In addition, smaller responses in 6 patients showed tumor regression of 10% and 30% were observed with embroidered with the disease for a maximum period of 14 months with continued treatment. Preferences INDICATIVE median progression-free survival was reported to be free from at least six months, many patients still take treatment. Based on these encouraging Phase I data, Plexxikon has a Phase II clinical study in 100 patients, which began in September 2009 and completed in January 2010, the assessment of the compound began in a Phase III study of 700 patients.
The side effects on the h Was reported most common, PLX4032 rash, pain, fatigue, sensitivity to light and joints that were reported in at 1120 mg twice a day, but these were considered mild and transient. Analysis of the results of Phase I studies have shown the development of epidermal carcinoma Keratoacanthomas and in 23% of patients who had a serious side effect of the drug be nnte k. A recent study has also shown that PLX4032 active ERK and increased ht Proliferation and migration of melanoma cells with wild-type B-RAF. Although PLX4032 is claimed to be a selective inhibitor V600EB RAF, it remains controversial whether clinical efficacy due to its selective inhibition of RAF V600EB or if the inhibition of the target au He V600EB RAF. PLX 4032 k Nnte induction of nonmelanoma skin cancer due to the activation of ERK be in normal cells.
Concerns PLX4032 is further reported that complicated by the formation of RAF RAF C V600EB V600EB RAF RAF dimers and C, which adversely the activation of MEK / ERK Chtigt suppressed. The C-mediated inhibition of RAF k Nnte one Descr RAF V600EB entering a dynamic state Restriction due physically with RAF C, which does not occur with one or wild-type RAF RAF as interact ancients were reports that RAF RAF CB the activity t and the phosphorylation of MEK in fibroblasts obtained ht, suggesting RAF C has the potential negatively modulate MAPK signaling under certain conditions. RAF C expression is compared to B RAF in cells at an early stage human melanoma V600EB RAF expressing reduced. In contrast, the metastatic cell lines have increased levels of the protein B of the RAF ht and thus a reduction of the RAF C: B-RAF report overcome oppression V600EB RAF k Nnte. Therefore, this experimental observation important ra