Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Murine melanoma cells treated with the melanocyte-stimulating hormone (MSH) family of peptides undergo differentiation characterized by enhanced melanogenesis and altered morphology. These effects are mediated via the adenylate cyclase-cAMP pathway leading to activation of protein kinase A (PKA). We have discovered that inhibition of a post-translational modification of chromatin proteins, viz. poly(ADP-ribosylation), also induces melanogenesis and differentiation in these cells. A range of competitive inhibitors (benzamide and its derivatives) of the nuclear enzyme poly(ADP-ribose) polymerase (PADPRP; EC 2.4.2.30) was utilized, and their ability to induce melanogenesis reflected their potency as PADPRP inhibitors. These compounds induced melanogenesis at low doses (20 microM-2 mM) which did not affect cell growth or viability. Induction of melanogenesis was not attributable to inhibition of cyclic nucleotide phosphodiesterase by these compounds. MSH treatment caused a transient rise in cAMP levels (up to 200-fold by 5 min and returning to near basal levels by 5 h). It also stimulated PKA activity up to 5-fold, and the temporal kinetics of this activation mirrored the changes in cAMP levels. In comparison, the PADPRP inhibitors had no effect on either of these processes. These data constitute a novel demonstration of a cAMP-independent mechanism for the induction of melanoma cell differentiation, including melanogenesis.
 ...
PMID:Murine melanoma cell differentiation and melanogenesis induced by poly(ADP-ribose) polymerase inhibitors. 132 52

Tiapride, a substituted benzamide, exerts an antalgic effect in man. To examine the possibility that tiapride analgesia might be related to a mechanism involving a release of endogenous opioids, the acute effects of an intravenous injection of the drug on plasma radioimmunoassayable beta-endorphin were studied in patients with pain from cancer (placebo-tiapride double-blind randomized trial). Seeing that substituted benzamides affect prolactin secretion, the plasmatic levels of prolactin and dopamine, a known factor inhibiting prolactin release, were studied as well. The tiapride infusion produced a slight but significant increase in plasma beta-endorphin level, an early and significant increase in plasma prolactin, and a sudden and highly significant decrease in plasma dopamine. These results are compatible with the hypothesis that tiapride influences the neuroendocrine system.
 ...
PMID:Effects of tiapride infusion on plasma levels of beta-endorphin, prolactin and dopamine in patients with pain from cancer. 626 2

Tiapride, a substituted benzamide, exerts an antalgic effect in man. To examine the possibility that tiapride analgesia might be related to a mechanism involving a release of endogenous opioids, the acute effects of an intravenous injection of the drug on plasma radioimmunoassayable beta-endorphin were studied in patients with pain from cancer (placebo-tiapride double-blind randomized trial). Seeing that substituted benzamides affect prolactin secretion, the plasmatic levels of prolactin and dopamine, a known factor inhibiting prolactin release, were studied as well. The tiapride infusion produced a slight but significant increase in plasma beta-endorphin level, an early and significant increase in plasma prolactin, and a sudden and highly significant decrease in plasma dopamine. These results are compatible with the hypothesis that tiapride influences the neuroendocrine system.
 ...
PMID:[Effects of tiapride infusion on plasma levels of beta-endorphin, prolactin and dopamine in patients with pain from cancer (author's transl)]. 626 92

Aldosterone synthase (CYP11B2) inhibitors have been explored in recent years as an alternative therapeutic option to mineralocorticoid receptor (MR) antagonists to reduce elevated aldosterone levels, which are associated with deleterious effects on various organ systems including the heart, vasculature, kidney, and central nervous system (CNS). A benzamide pyridine hit derived from a focused screen was successfully developed into a series of potent and selective 3-pyridyl isoindolin-1-ones CYP11B2 inhibitors. Our systematic structure-activity relationship study enabled us to identify unique structural features that result in high selectivity against the closely homologous cortisol synthase (CYP11B1). We evaluated advanced lead molecules, exemplified by compound 52, in an in vivo cynomolgus monkey acute adrenocorticotropic hormone (ACTH) challenge model and demonstrated a superior 100-fold in vivo selectivity against CYP11B1.
 ...
PMID:Discovery of 3-Pyridyl Isoindolin-1-one Derivatives as Potent, Selective, and Orally Active Aldosterone Synthase (CYP11B2) Inhibitors. 3253 Jun 24