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Ribavirin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Emily Woolnough, Amanda Wade, Joe Sasadeusz
In an animal model, ribavirin alone or in combination with tiazofurin (an investigational inhibitor of IMPDH being studied for the treatment of cancer) reduced the clinical and histopathological signs of experimental autoimmune encephalomyelitis (an animal model of multiple sclerosis) (Lavrnja et al., 2005).
Cellular Oncogenes as Biotherapeutic Targets for the Differentiation and Inhibition of Cancer Cells
Published in Robert I. Glazer, Developments in Cancer Chemotherapy, 2019
Robert I. Glazer, Angelo Aquino, Gang Yu
Apart from the more commonly used differentiating agents such as DMSO, TPA, l,25(OH)2D3, and retinoic acid, a diverse spectrum of other compounds elicits morphologic changes in HL-60 cells.1 In general, the more cytotoxic the drug, the less differentiation occurs, and the narrower the dose-response relationship. Antimetabolite drugs such as the nucleoside analogs 5-azacytidine37 and neplanocin A (Figure 1),38,39 which preferentially inhibit the methylation of DNA and RNA respectively, induce a partial differentiation response in HL-60 cells mainly because of their potent cytocidal activities (Figure 2). Cell cycle specificity also plays a role in differentiation. The agents DMSO and retinoic acid generally produce an accumulation of cells in the G0/G1 phase of the cell cycle,40,41 an event which accompanies or precedes differentiation. The cytidine analog cyclopentenyl cytidine (CTP) (Figure 1) produces a rapid induction of mature myeloid cells upon treatment of HL-60 cells due to its ability to inhibit CTP synthesis, rapidly inhibit DNA synthesis, and inhibit cells from traversing S phase (Figure 2).42,43 The latter effect on HL-60 cells is also expressed by other inhibitors of CTP synthetase such as carbodine42 and 3-deazauridine,44 and by pyrazofurin, an inhibitor of orotidylate decarboxylase.44 Drugs which inhibit purine synthesis de novo such as the IMP dehydrogenase inhibitors tiazofurin and mycophenolic acid appear to be less effective inducers of myeloid differentiation in HL-60 cells.44,45
Newer human inosine 5′-monophosphate dehydrogenase 2 (hIMPDH2) inhibitors as potential anticancer agents
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Chetan P. Shah, Prashant S. Kharkar
Mycophenolic acid (MPA) 1 (Figure 1), a natural product, is a reversible, potent, uncompetitive inhibitor of IMPDH and known to be an anticancer and immunosuppressive agent. Mycophenolate mofetil (MMF, 2, a prodrug of MPA), has been approved for the treatment of acute allograft rejection following kidney transplant. The MPA and its related forms MMF or MPA sodium (3) (MPS) cause dose-limiting gastrointestinal (GI) toxicity. However, adverse effects related to the treatment with MPA-based drugs, such as diarrhoea, leukopenia, sepsis and vomiting, are the barriers to the administration of higher doses and more effective treatment21. The competitive IMPDH inhibitors such as tiazofurin (4), ribavirin (5) and mizoribine (6) (after intracellular activation by phosphorylation) are nucleoside analogues and derivatives thereof22 have unfavourable tolerability profiles too. Thus, there is a urgent need for newer, safer, potent and orally bioavailable IMPDH inhibitors23,24.
Protein tyrosine phosphatase 1B (PTP1B) inhibitors as potential anti-diabetes agents: patent review (2015-2018)
Published in Expert Opinion on Therapeutic Patents, 2019
Hidayat Hussain, Ivan R Green, Ghulam Abbas, Sergazy M Adekenov, Wahid Hussain, Iftikhar Ali
Thiazole is an interesting heterocycle comprising nitrogen and sulfur, and has played a major role in medicinal chemistry. It is also present in many natural compounds such as Thiamine and Vitamin B1 and also in bioactive synthetic compounds. Notably, this scaffold is present in many drugs viz., penicillin, sulfazole (antimicrobial), ritonavir (antiretroviral), abafungin (antifungal), and tiazofurin (anticancer) [73,74]. Notably, there are a large number of thiazole comprising antidiabetic drugs that have been reported with reduced side effects viz., rosiglitazone, DRF-2519, netoglitazone, PHT46, pioglitazone, DRF-2189, and PMT13 [75].