Trypanosoma brucei Glycogen Synthase Kinase-3, A Target for Anti-Trypanosomal Drug Development: A Public-Private Partnership to Identify Novel Leads
| dc.contributor.author | Oduor, R.O. | |
| dc.contributor.author | Kayode, K. Ojo | |
| dc.contributor.author | Gareth, P. Williams | |
| dc.contributor.author | Francois, Bertelli | |
| dc.contributor.author | James, Mills | |
| dc.contributor.author | Louis, Maes | |
| dc.contributor.author | David, C. Pryde | |
| dc.contributor.author | Tanya, Parkinson | |
| dc.contributor.author | Wesley, C. Van Voorhis | |
| dc.contributor.author | Tod P., Holler | |
| dc.date.accessioned | 2012-09-21T09:27:33Z | |
| dc.date.available | 2012-09-21T09:27:33Z | |
| dc.date.issued | 2012-09-21 | |
| dc.description | PLoS Neglected Tropical Disease | |
| dc.description.abstract | Background: Trypanosoma brucei, the causative agent of Human African Trypanosomiasis (HAT), expresses two proteins with homology to human glycogen synthase kinase 3b (HsGSK-3) designated TbruGSK-3 short and TbruGSK-3 long. TbruGSK- 3 short has previously been validated as a potential drug target and since this enzyme has also been pursued as a human drug target, a large number of inhibitors are available for screening against the parasite enzyme. A collaborative industrial/ academic partnership facilitated by the World Health Organisation Tropical Diseases Research division (WHO TDR) was initiated to stimulate research aimed at identifying new drugs for treating HAT. Methodology/Principal Findings: A subset of over 16,000 inhibitors of HsGSK-3 b from the Pfizer compound collection was screened against the shorter of two orthologues of TbruGSK-3. The resulting active compounds were tested for selectivity versus HsGSK-3b and a panel of human kinases, as well as in vitro anti-trypanosomal activity. Structural analysis of the human and trypanosomal enzymes was also performed. Conclusions/Significance: We identified potent and selective compounds representing potential attractive starting points for a drug discovery program. Structural analysis of the human and trypanosomal enzymes also revealed hypotheses for further improving selectivity of the compounds. | en_US |
| dc.identifier.uri | http://ir-library.ku.ac.ke/handle/123456789/5520 | |
| dc.language.iso | en | en_US |
| dc.subject | ||
| dc.title | Trypanosoma brucei Glycogen Synthase Kinase-3, A Target for Anti-Trypanosomal Drug Development: A Public-Private Partnership to Identify Novel Leads | en_US |
| dc.type | Article | en_US |