14 research outputs found
A strategy to discover new organizers identifies a putative heart organizer
Organizers are regions of the embryo that can both induce new fates and impart pattern on other regions. So far, surprisingly few organizers have been discovered, considering the number of patterned tissue types generated during development. This may be because their discovery has relied on transplantation and ablation experiments. Here we describe a new approach, using chick embryos, to discover organizers based on a common gene expression signature, and use it to uncover the anterior intestinal portal (AIP) endoderm as a putative heart organizer. We show that the AIP can induce cardiac identity from non-cardiac mesoderm and that it can pattern this by specifying ventricular and suppressing atrial regional identity. We also uncover some of the signals responsible. The method holds promise as a tool to discover other novel organizers acting during development
Synthesis and Antiobesity Properties of 6‑(4-Chlorophenyl)-3-(4-((3,3-difluoro-1-hydroxycyclobutyl)Âmethoxy)-3-methoxyphenyl)Âthieno[3,2‑<i>d</i>]pyrimidin-4(3<i>H</i>)‑one (BMS-814580): A Highly Efficacious Melanin Concentrating Hormone Receptor 1 (MCHR1) Inhibitor
The potent MCHR1 in vitro and in vivo
antagonist activity of a series of cyclic tertiary alcohols derived
from compound <b>2b</b> is described. Subsequent pharmacokinetic
and pharmacodynamic studies identified BMS-814580 (compound <b>10</b>) as a highly efficacious antiobesity agent with a relatively
clean in vitro and in vivo safety profile