| Title |
Discovery of structurally diverse natural product antagonists of chemokine receptor CXCR3
|
|---|---|
| Published in |
Molecular Diversity, January 2005
|
| DOI | 10.1007/s11030-005-1296-8 |
| Pubmed ID | |
| Authors |
John G. Ondeyka, Kithsiri b. Herath, Hiranthi Jayasuriya, Jon D. Polishook, Gerald F. Bills, Anne W. Dombrowski, Marina Mojena, Gregory Koch, Jerry DiSalvo, Julie DeMartino, Ziqiang Guan, Weerachai Nanakorn, Cori M. Morenberg, Michael J. Balick, Dennis W. Stevenson, Marc Slattery, Robert P. Borris, Sheo B. Singh |
| Abstract |
The chemokines (CXCL9, CXCL10 and CXCL11) and associated CXCR3 receptor are expressed during the inflammatory process from multiple sclerosis, atherosclerosis or organ transplantation resulting in the recruitment of lymphocytes leading to tissue damage. It is hypothesized that blocking of the ligand/CXCR3 receptor interaction has potential to provide opportunity for development of agents that would block tissue rejection. In this paper, four classes of natural product inhibitors (IC50 ranging 0.1-41 microM) have been described that block the CXCR3 receptor interaction of IP-10 ligand. These include a cyclic thiopeptide (duramycin), polyketide glycosides (roselipins), steroidal glycosides (hypoglausin A and dioscin) and a novel alkyl pyridinium alkaloid that were isolated by bioassay-guided fractionation of the organic extracts derived from actinomycete, fungal, plant and marine sources and discovered using 125I IP-10/CXCR3 binding assay. Duramycin was the most potent with an IC50 of 0.1 microM. Roselipins 2A, 2B and 1A showed IC50 values of 14.6, 23.5, and 41 microM, respectively. Diosgenin glycosides dioscin, hypoglaucin A and kallstroemin D exhibited IC50 values of 2.1, 0.47 and 3 microM, respectively. A novel cyclic 3-alkyl pyridinium salt isolated from a sponge displayed a binding IC50 of 0.67 microM. |
Mendeley readers
The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 22 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 8 | 36% |
| Student > Bachelor | 3 | 14% |
| Other | 2 | 9% |
| Student > Doctoral Student | 1 | 5% |
| Student > Ph. D. Student | 1 | 5% |
| Other | 3 | 14% |
| Unknown | 4 | 18% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 4 | 18% |
| Medicine and Dentistry | 3 | 14% |
| Chemistry | 3 | 14% |
| Biochemistry, Genetics and Molecular Biology | 2 | 9% |
| Social Sciences | 2 | 9% |
| Other | 3 | 14% |
| Unknown | 5 | 23% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 December 2013.
All research outputs
#7,434,249
of 22,727,570 outputs
Outputs from Molecular Diversity
#129
of 461 outputs
Outputs of similar age
#35,958
of 139,467 outputs
Outputs of similar age from Molecular Diversity
#3
of 6 outputs
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So far Altmetric has tracked 461 research outputs from this source. They receive a mean Attention Score of 3.2. This one is in the 49th percentile – i.e., 49% of its peers scored the same or lower than it.
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