Resulting in a degradation by the proteasome enzymes. Get the first Hsp90 inhibitor in clinical development Elesclomol STA-4783 was the geldanamycin derivative 17 allylamino demethoxygeldanamycin 17th HSP 90 inhibitors go Ren 17, two formulations of AAG and IPI tanespimycin 504th Synthetic HSP 90 inhibitors are also under development Lich Including the purine-scaffold Hsp90 inhibitor CNF2024/BIIB021, isoxazole derivative and carbazole VER 52296/NVP AUY922 benzamide derivative SNX 1 April 5422nd A third type of Hsp90 is developed by the pharmaceutical company Synta, STA 9090th This is an inhibitor of HSP 90 has nothing to do with the ansamycin family and is the subject of Phase II clinical trials for patients with GIST. Two phase II studies are underway to AUY 933, isoxazole derivative of 17-AAG in the treatment of refractory GIST Ren.
STA 9090 is a novel second-generation, resorcinol-containing triazole inhibitor of heat shock protein that has shown the F Ability, multiple kinases with comparable efficacy to inhibit, and a broader profile than the activity t, inhibitors of specific kinases, BI 2536 such as imatinib , erlotinib, and sunitinib in pr clinical trials. STA 9090 binds to the ATP binding pocket at the N-terminus of the Hsp90 protein and acts as a potent inhibitor of Hsp90. STA 9090 showed the power of 10 to 100 times that of the family of HSP90 inhibitors geldanamycin and activity t against a broad spectrum of kinases. In vivo models have demonstrated a high efficiency over a wide range of cancers, including tumors resistant to Gleevec, Tarceva, and Sutent.
The Phase II studies are underway to its efficacy in the treatment of patients with metastatic disease and / or inoperable, the re To determine U prior treatment with imatinib or sunitinib. Based on an unparalleled knowledge of cancer genes, it is now m Possible to disable the signaling mechanisms of tumor cells without the normal tissues by targeted therapy. Like the first time by developing a small molecule antagonist of the BCR-ABL, ie, imatinib, a targeted cancer therapy m Possible, and in some F Cases, dramatic clinical responses. However, centers the underlying concept of drug research is based on the target high-throughput screening of potential siRNA libraries contain molecules proved to be difficult to generalize. Co Teux, labor-intensive and low performance target of drug discovery-based produce promising drugs that have minimal or no gains in the tests provided in the clinic.
May be this high rate of failure the extreme heterogeneity t the mutated tumors, even seemingly identical, with hundreds of genes, verst RKT or deregulated. This complexity t making it difficult to identify a single, driving, signaling for therapeutic intervention, and gives cause for concern that imatinib may be realized as an approach to drug development in only a handful of tumors. To overcome these obstacles, efforts have begun, the tools of systems biology to study cancer pathways model that interconnected global networks. Cards such as connectivities t, connection of multiple signaling pathways, perhaps more accurately reproduce the tactics tumor responsible for the failure of the treatment of confinement Lich redundancy, buffering, and modularity in t semiautonomous subnetworks. This information k Can be exploited to identify new drug discovery for inh-oriented manner