Chemical probes portal, a crowdsourcing site to combat bad data

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(Last Updated On: April 23, 2017)
Chemical probes synthesized at broad institute

Chemical biologist hoping that the new crowdsourcing portal will help improve the information about small, druglike chemical probes to study different proteins responsible for human health and disease. Credit: Len Rubenstein/The Broad Institute

Chemists and biochemists have launched a crowdsourcing site entitled “Chemical Probes Portal” to combat bad data. According to the report released by a panel of international research experts from 46 different nonprofit institutions, universities, and biotech/pharmaceutical companies, it is necessary to design an online portal where chemical probes can be deposited.

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The issues related to fault chemical probes has been growing rapidly in recent years and therefore, researchers said that setting up an online crowdsourcing portal will be much like a TripAdviser which can disseminate up-to-date information about different chemical probes.

The chemical probes

The chemical probes are the small drug-like molecules that are primarily used to block the activity of a specific type of protein to determine the role of that protein in biochemistry. Blocking such specific protein using a chemical probe helps researchers design new drug compounds that perform the similar function but retains some of the important activities such as nontoxicity and the ability to travel throughout the body.

In the present, there are thousands of such probes but most of them have the side effect such as they interact with nontarget proteins as well as unwanted off-target effects. Therefore it has become a serious problem. Paul Workman, who is a chemical biologist and the chief executive of the Institute of Cancer Research in London, said that many of the chemical probes present now a day produce spurious results that may lead the researchers to the wrong conclusion about the protein and drug molecule which they are studying.

As, for example, some probes have been found to produce side effects such as chemical changes in the proteins or causing protein aggregation. Several years ago there was an incident during which a poor chemical probe data led the researchers to pursue a final stage of clinical trials on a cancer drug probe called as iniparib. That trial cost hundreds of millions of dollars. Later on, in 2011, iniparib was found to be less effective in hitting the target molecule than it was thought before and was declared as a failure.

In spite of these failures, researchers still continue to use such faulty probes. This is because, the chemical biologists still relies on the normal, self-correcting mechanisms of science; published journal articles, reviews, and conference papers to set their record straight.

Workman said that the self-correction is not effective enough. He also mentioned that there are few researchers who have the time or expertise to keep the track record of exactly which probes are providing successful results.

The self-correlation mechanism

Workman said, most of the researchers simply go to the Google Scholar and search for the probes that have a large number of citations. However, these probes are often older and less reliable because they are not up-to-date. One of such example of the chemical probe is LY94002 which has been cited 30,000 times since 1994 and 1100 times since 2014.

However, it is a terrible compound. Workman said that this probe is 10 years of out of date and has many off-target effects. Though most accurate probes are available in the market for years, but still researchers use LY94002 because it appears to have a strong track record.

The crowdsourcing portal

Chemical biologists say now they hope this crowdsourcing portal will solve these problems. This crowdsourcing portal entitled “Chemical Probes Portal” which has backups from Institute of Cancer Research, the Broad Institute, the Structural Genomic Consortium and the Wellcome Trust. On this site, researchers will submit their chemical probes with their annotations. This will ensure that their colleagues are most up to date with the comparative information of different chemical probes they need to study.

Kevan Shokat, a chemical biologist at the University of California, San Francisco said that this effort could be challenging. This is because, even though the researchers used the same chemical probe for the study, but the study conditions and doses are different in each study. However, he added, as long as researchers used the portal in such a way to improve the understanding of different probes it will surely help the community.

Reference article: American association for the advancement of sciences

Article doi: 10.1126/science.aac8886

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