Synthesis and pharmacological evaluation of the stereoisomers of 3-carba cyclic-phosphatidic acid
Graphical abstract
The first stereochemical synthesis and pharmacological evaluation of 18:1 3CCPA is described.
Section snippets
Acknowledgments
This research was supported by NIH Grant CA92160 (G.T.), Van Vleet Professorship (D.M.), Breast Cancer Research Foundation (N.P.) and Lpath Inc. (G.M.).
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2015, Progress in Lipid ResearchCitation Excerpt :1-Linoleoyl and 1-oleoyl lysophosphatidic acid [261], and various thiophosphate derivatives, such as acetal derivative 9 (IC50 252 nM, LPC assay), have been reported to inhibit ATX [262–264]. Another class of ATX inhibitors is based on cPA [265–269], which contains a five-membered ring between the sn-2 hydroxy group and the sn-3 phosphate. Typical example is the carba cPA analog 10 (3ccPA 18:1, IC50 294 nM, bis-pNPP assay), which succeeded in inhibiting the pulmonary metastasis of B16F10 melanoma cells in mice [265].
Vinyl sulfone analogs of lysophosphatidylcholine irreversibly inhibit autotaxin and prevent angiogenesis in melanoma
2015, Bioorganic and Medicinal ChemistryCurrent progress in non-Edg family LPA receptor research
2013, Biochimica et Biophysica Acta - Molecular and Cell Biology of LipidsCitation Excerpt :The possibility that these compounds have agonistic activity on the LPA5 receptor should be examined because this would also be consistent with their anti-cancer effects. The activity on the LPA5 receptor and possible therapeutic impacts should be considered in the further development of anti-cancer drugs which target ATX and LPA receptors [100,101]. LPA functions in the initiation of neuropathic pain [102], and the roles of ATX [103], LPA1 [104], and LPA3 [105] in this process have been investigated in studies utilizing knockout mice.
Pharmacological evaluation of a novel cyclic phosphatidic acid derivative 3-S-cyclic phosphatidic acid (3-S-cPA)
2012, Bioorganic and Medicinal ChemistryCitation Excerpt :The dose-response relationship of ATX inhibition showed no significant difference between (R)-(+)-3-S-cPA 1a and (S)-(−)-3-S-cPA 1a, indicating that the chirality of 3-S-cPA 1a did not affect the degree of ATX inhibition. This result was consistent with the previous report that no stereoselective differences were observed between the enantiopure 2ccPA and 3ccPA with respect to inhibition of ATX.17,18,20 In this study, we clarified the effect of 3-S-cPA on the following biological functions, which are known to be specific biological activities of cPA: (1) inhibition of cancer cell migration, (2) suppression of the nociceptive reflex, and (3) attenuation of ischemia-induced delayed neuronal cell death.