Navigation Links
Mapping of protein inhibitors facilitates development of tailor-made anticancer agents

A team of researchers at Karolinska Institutet in Sweden has generated a map over the effects of small drug-like molecules on PARP1 and other similar proteins in the body. This map may explain the mechanism behind putative side effects of the so-called PARP inhibitors, and can play an important role in the development of novel tailor-made cancer drugs. The study is presented in the journal Nature Biotechnology, and will hopefully contribute to new cancer therapies with fewer detrimental side effects.

PARP1 is a protein with enzymatic activity that governs repair of DNA damage in our cells. In the past decade, PARP1 has been in the focus for a large number of industrial drug development projects, primarily targeting breast and ovarian cancers. More than 50 clinical studies have been initiated around the world.

In the current study, the researchers at Karolinska Institutet have tested the effects of small drug-like molecules inhibitors on PARP1 and other enzymes of the same class. The effects of 180 substances on 13 different human PARP enzymes were studied. Many of the drugs that are currently being tested in clinical studies were part of the survey.

"Our results give us a map over the effects of a number of known but also less well characterized drug-like compounds on different PARP enzymes", says Herwig Schler, who headed the study at the Department of Medical Biochemistry and Biophysics. "Studying the cross-reactivity of less well characterized compounds on different PARP enzymes is especially interesting, since it can give clues to the interpretation of clinical side effects."

The chemical interaction map was complemented with high-resolution structural information, showing at atomic detail how inhibitors bind to these PARP enzymes. Together, the results give unique insights into specificity and cross-reactivity of PARP inhibitors. This in turn will be an important hallmark toward development of selective PARP inhibitors tailor-made substances that can inhibit one PARP enzyme while leaving the others unaffected.

This project builds upon a long-standing industry collaboration that Karolinska Institutet has participated in within the Structural Genomics Consortium 2005-2010. The study published in Nature Biotechnology is the result of collaboration between the research group at KI, the University of Perugia (Italy), Actar AB, and GE Healthcare.


Contact: Katarina Sternudd
Karolinska Institutet

Related medicine news :

1. CSHL team introduces automated imaging to greatly speed whole-brain mapping efforts
2. Fast new method for mapping blood vessels may aid cancer research
3. Blood vessel mapping reveals 4 new ZIP codes
4. Gene Mapping Reveals Clues to Bedbugs Pesticide Resistance
5. Roadmap published for dynamic mapping of estrogen signaling in breast cancer
6. Mapping faculty social networks helps female faculty move ahead at NJIT
7. Mapping a brain atlas
8. ELLKAY Introduces Revolutionary Live Insurance Mapping Solution for Diagnostic Laboratories
9. A single protein helps the body keep watch over the Epstein-Barr virus
10. CD97 gene expression and function correlate with WT1 protein expression and glioma invasiveness
11. Protein structures give disease clues
Post Your Comments:
(Date:11/28/2015)... ... November 28, 2015 , ... Trying to relax on a couch can ... "I conceived of this design due to personal experience with a bad back," he ... relaxation and convenience, as well as increases support. It also makes it easier to ...
(Date:11/27/2015)... CA (PRWEB) , ... November 27, 2015 , ... According ... carried out by the University of Toronto and the University of British Columbia suggested ... hospitalizations for head injuries. The article explains that part of the reason for the ...
(Date:11/27/2015)... ... November 27, 2015 , ... "When ... said an inventor from Hillside, N.J. "Many people catch diseases simply from sitting ... individuals will always be protected from germs." , He developed the patent-pending QUDRATECS ...
(Date:11/27/2015)... ... 27, 2015 , ... Consistent with the Radiology Business ... Better Radiology Marketing Programs meeting will showcase some of the best 2015 ... Caesars Palace in Las Vegas with a pre-conference session on a collaborative approach ...
(Date:11/27/2015)... ... November 27, 2015 , ... CBD College is proud to ... Programs (CAAHEP) awarded accreditation to its Diagnostic Medical Sonography program. CBD College is honored ... one of twelve colleges and universities in the state of California make the cut. ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... 2015 ) ... "Radioimmunoassay Market by Type (Reagents & Kits, ... Clinical Diagnostic Labs), Application (Research, Clinical Diagnostics), ... report to their offering. --> ... of the "Radioimmunoassay Market by Type ...
(Date:11/25/2015)... 2015 ... "Global Brain Monitoring Devices Market 2015-2019" ... ) has announced the addition ... Market 2015-2019" report to their offering. ... ) has announced the addition of ...
(Date:11/25/2015)... 2015  Amgen (NASDAQ: AMGN ) today announced ... the United States (U.S.) Food ... candidate to Humira ® (adalimumab). Amgen believes this ... the FDA and represents Amgen,s first BLA submission using ... , M.D., executive vice president of Research and Development ...
Breaking Medicine Technology: