The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
A Pt(IV) Pro-drug Preferentially Targets Indoleamine-2,3-dioxygenase, Providing Enhanced Ovarian Cancer Immuno-Chemotherapy
Open accessAbstract
Expression of indoleamine-2,3-dioxygenase (IDO), an immunosuppressive enzyme in human tumors, leads to immune evasion and tumor tolerance. IDO is therefore a tumor immunotherapeutic target, and several IDO inhibitors are currently undergoing clinical trials. IDO inhibitors can enhance the efficacy of common cancer chemotherapeutics. Here we investigate Pt(IV)-(D)-1-methyltryptophan conjugates 1 and 2 for combined immunomodulation and DNA cross-link-triggered apoptosis for cancer "immuno-chemotherapy". Compound 2 effectively kills hormone-dependent, cisplatin-resistant human ovarian cancer cells, inhibiting IDO by transcriptional deregulation of the autocrine-signaling loop IDO-AHR-IL6, which blocks kynurenine production and promotes T-cell proliferation. Additionally, 1 and 2 display low toxicity in mice and are stable in blood. To our knowledge, this construct is the first Pt drug candidate with immune checkpoint blockade properties.
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Metadata
- Authors
- Awuah, S. G., Zheng, Y.-R., Bruno, P. M., Hemann, M. T., & Lippard, S. J.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2015-11-18
- Volume
- 137
- Issue
- 47
- Pages
- 14854-14857
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2289081179
- Cited by
- 164
- References
- 9
- FWCI
- 5.59
- Type
- journal article
- Language
- en
- Open access
- green
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- Awuah, S. G., Zheng, Y.-R., Bruno, P. M., Hemann, M. T., & Lippard, S. J. (2015). A Pt(IV) Pro-drug Preferentially Targets Indoleamine-2,3-dioxygenase, Providing Enhanced Ovarian Cancer Immuno-Chemotherapy. Journal of the American Chemical Society. https://doi.org/10.1021/jacs.5b10182
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