I just went through some TZD literature. Takeda is testing a TZD called
pioglitazone (also called AD-4833 in the scientific literature). Smith
Kline Beecham is testing another TZD called BRL49653 in the scientific
literature. Merck is working on AD-5075 but I don't know if clinical
trials have begun yet. The only approved TZD is Rezulin which is also
called troglitizone or CS-045. In animal studies, Rezulin is the
weakest. Other TZD that pop up in the literature include ciglitazone,
englitizone, dardlitizone, and CP-86,325. All of these TZDs appear to
act through PPAR gamma. However, it appears that the natural ligand
(hormone) for PPAR gamma is 15-deoxy-delta 12,14 prostaglandin J2.
In animal models of diabetes, Targretin and ALRT268 (two rexinoids) have been shown to synergize with BRL49653 (a second generation TZD). In human liposarcoma studies, rexinoids have been shown to synergize with Pioglitazone, another 2nd generation TZD.
The human cells show that Rexinoids can synergize with 2nd generation TZDs in humans. The mouse data shows that synergy can happen between rexinoids and another 2nd generation TZD (to lower glucose, insulin, and triclyceride levels). |
