The development direction of Heat shock protein (HSP) 90 inhibitor

Heat shock protein 90 (HSP90), a molecular target for cancer, has a history of more than 10 years. HSP90 is one of the most active chaperone proteins in cell, which not only involves in the folding and activation of a variety of proteins, but also regulates the transportation of numerous proteins and takes part in the signal transduction of cells. Inhibit the expression of HSP90 prevents tumor metabolism and conducting these downstream genes.

The first generation of HSP90 inhibitor includes Geldanamyvin (GM) and Radicicol (RD), both of which inhibit the function of Hsp90 by binding to the unusual ADP/ATP-binding pocket of the protein. However, due to the poor stability and a serious liver toxicity of first-generation HSP90 inhibitors, the medicinal chemists are therefore committed to develop the second generation of HSP90 inhibitors. Currently, the HSP90 inhibitors that entering Phase III clinical trials include Ganetespib of Synta pharmaceutical and Retaspimycin of Infinity and another dozen drugs. But most of them have unsatisfactory clinical efficacy which indicated that HSP90 inhibitors may not be the broad-spectrum anti-cancer drugs.

The key reason for HSP90 inhibitors’ poor clinical response is that the tumor biology study of HSP90 is seriously falling behind. Firstly, the biological mechanisms of HSP90 leading to tumor development is still not clear. Furthermore, Hsp90may not be the pivotal gene (such as BCR-ABL, HER2, EGFR) in tumor development, so it have limited effectiveness in the expression and the signal transduction of other genes tumor related genes. So HSP90 inhibitors could be developed as the second line drugs in patients that are resistant to other anti-cancer drugs, or find the special intended people.

Up to now, 25 new drugs has gained the FDA's green channel; analysts expect that this year is expected to break the record of 43 new drugs approved in 2013.

However, it is interesting that no blockbuster drugs have been approved in 2014 and the biggest drug was actually the PDE4 inhibitors Otezla from Celgene Corporation. Otezla has gained the FDA approval for the treatment of psoriatic arthritis in March this year with the sales expected to contribute only $ 92.7 million in the future 5 years. Even so, some people still doubt about whether its effectiveness matches its expensive price.

In fact, the PD-1 antibody tumor drugs and the hepatitis C drugs developed respectively by AbbVie and Gilead are two attractive themes in this year’s biomedical market. The hepatitis C drug Sovaldi has swept the major pharmaceutical sales list since approved last year.

At the same time, the development of cancer immunotherapy drugs is also in the golden age. Pembrolizumab, a drug developed by Merck and used for the treatment of melanoma, will be approved in Oct. 28 this year. Nivolumab, a new antibody drug of Bristol-Myers Squibb, was approved this year for the treatment of melanoma, renal cell carcinoma and non-small cell lung cancer and is expected to become the next major breakthrough in the field of cancer immunotherapy. The sustained response rate of Nivolumab to multiple cancers reached 20% -30%. The new drug breakthrough the sustained tumor response rate of 10% -15%, which has been impede the development of cancer immunotherapy.

Numerologist Warda is hooked on OG-L002 fishing, collecting. And lastly her encouragement comes from socializing along with her companions.