TEI-A00114: a new vitamin D3 analogue that inhibits neutrophil recruitment in an acute lung injury hamster model while showing reduced hypercalcemic activity.

While searching for vitamin D(3) analogues which inhibit neutrophil recruitment in the lung without elevating plasma calcium level, we found that (5Z,7E)-(1S,3R)-20(R)-[(5E)-(2S)-2-hydroxy-2-methyl-cyclopentanone-5-ylidene]methyl-9,10-secopregna-5,7,10(19)-triene-1,3-diol (TEI-A00114) had the best efficacy and calcemic action. TEI-A00114 has a vitamin D receptor affinity 2.5-fold weaker and a vitamin D binding protein affinity 330.

Antitumor activity, optimum administration method and pharmacokinetics of 13,14-dihydro-15-deoxy-deoxy-Delta7 -prostaglandin A1 methyl ester (TEI-9826) integrated in lipid microspheres (Lipo TEI-9826).

13,14-Dihydro-15-deoxy-Delta7-prostaglandin A1 methyl ester (TEI-9826), an antitumor prostaglandin analog, is a candidate for clinical trial. In the present study, we examined its biological stability in vitro, antitumor activity in vitro and in vivo, and pharmacokinetics. Although TEI-9826 was rapidly hydrolyzed to the carboxylic acid form (TOK-4528), TOK-4528 as well as Delta12-prostaglandin J2 (PGJ2) were found to be stable in rat, mouse and human serum in vitro.

Antitumor activity of 13,14-dihydro-15-deoxy-delta7-prostaglandin-A1-methyl ester integrated into lipid microspheres against human ovarian carcinoma cells resistant to cisplatin in vivo.

One of the delta7-prostaglandin A1 derivatives with unique antitumor activities, 13,14-dihydro-15-deoxy-delta7-prostaglandin-A1-methyl ester, was integrated into lipid microspheres (Lipo-TEI9826) and examined for its antitumor effect in vitro and in vivo. The in vitro relative resistance of human ovarian cancer, A2780CP, to cisplatin (CDDP) and Lipo-TEI9826 was 27.3 and 2.

Selective coupling of prostaglandin E receptor EP3D to multiple G proteins depending on interaction of the carboxylic acid of agonist and arginine residue of seventh transmembrane domain.

Prostaglandin E receptor EP3D is coupled to stimulation and inhibition of adenylate cyclase and stimulation of phosphatidylinositol turnover. To examine the roles of the interaction of the carboxylic acid of an agonist and its putative binding site, the arginine residue in the seventh transmembrane domain of EP3D, in receptor-G protein coupling, we have mutated the arginine to the non-charged glutamine. TEI-3356, an EP3 agonist with a negatively charged the carboxylic acid, and TEI-4343, a non-charged methylester of TEI-3356, inhibited the forskolin-stimulated cAMP formation in the same concentration-dependent manner, but stimulation of basal cAMP formation and Ca2+ mobilization by TEI-4343 was much lower than that by TEI-3356.

TEI-3356, a highly selective agonist for the prostaglandin EP3 receptor.

Recently, we cloned cDNAs for the three mouse PGE receptor subtypes, EP1, EP2 and EP3, and the prostacyclin receptor, and established cells that stably express each receptor. We examined the selectivity of TEI-3356, an isocarbacyclin analogue, compared with other EP agonists, sulprostone and misoprostol, using Chinese hamster ovary cells expressing each cloned receptor. TEI-3356 selectively displaced the [3H]PGE2 binding to EP3-expressing cell membranes, but showed very low affinity for both EP1 and EP2.