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Chemical Compound Review

CHEMBL2151429     ethyl2-[2- (difluoromethoxy)phenyl]-4...

Synonyms: SureCN9178940, CGP-28392, Ciba 28392, AC1L3XFJ, IOS 2456, ...
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Disease relevance of IOS 2456

  • The cardiovascular actions of this compound (with the exception of bradycardia) are not mediated through the autonomic nervous system, and interactions with other pharmacological agents suggest that CGP 28 392 has calcium channel activating properties [1].

High impact information on IOS 2456

  • The dihydropyridine derivatives CGP 28392 and BAY K 8644 exert a strong positive inotropic effect in mammalian cardiac muscle, presumably by increasing Ca influx during the action potential [2].
  • To study the mechanism of action of this putative calcium channel agonist, we have related the effects of CGP 28392 on contraction (measured with an optical video system) and radioactive calcium uptake to ligand-binding studies in cultured, spontaneously beating chick embryo ventricular cells [3].
  • Effects of the calcium-channel agonist CGP 28392 on insulin secretion from isolated rat islets of Langerhans [4].
  • Agonists Bay-K8644 and CGP-28392 open calcium channels reconstituted from skeletal muscle transverse tubules [5].
  • The systolic blood pressure of CGP 28392-treated pregnant rats rose transiently for 2 days and then declined toward values of nontreated pregnant controls, although remaining higher [6].

Biological context of IOS 2456


Anatomical context of IOS 2456

  • (-)-S-BAY K 8644, (+/-)-BAY K 8644, (+)-S-202-791 and CGP-28392 produced contractions in partially depolarized (15 mM K+) strips of guinea pig ileal longitudinal smooth muscle which differed in the degree of maximum contraction obtained [9].
  • In contrast, CGP 28392 produced no contraction in 14 of 19 tracheas (all ages combined) in the presence of aspirin; whereas, all 18 tracheas in the absence of aspirin contracted [10].
  • Calcium (Ca2+)-dependent action potentials were recorded from 22 mM potassium (K+)-depolarized guinea-pig papillary muscle at several different pacing frequencies in the absence and presence of CGP 28 392 (10 microM), a Ca2+ channel agonist [11].
  • Effects of calcium channel activators BAY-K8644 and CGP-28392 on steroidogenesis in granulosa cells of the domestic hen [12].
  • There is no addition between the effects of drugs activating the Ca2+ channel and the effects of depolarization suggesting that Bay K8644 and CGP 28392 work preferentially on polarized membranes [13].

Associations of IOS 2456 with other chemical compounds


Gene context of IOS 2456

  • Bay K 8644 or CGP 28392 alone had no effect on renin release from the slices, whereas both compounds produced a concentration-dependent inhibition of the release in the presence of 15 mM potassium [17].


  1. Cardiovascular effects of the nifedipine analog, CGP 28 392, in the conscious dog. Preuss, K.C., Cheung, N.L., Brooks, H.L., Warltier, D.C. J. Cardiovasc. Pharmacol. (1984) [Pubmed]
  2. Dihydropyridine derivatives prolong the open state of Ca channels in cultured cardiac cells. Kokubun, S., Reuter, H. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  3. Inotropic effect, binding properties, and calcium flux effects of the calcium channel agonist CGP 28392 in intact cultured embryonic chick ventricular cells. Laurent, S., Kim, D., Smith, T.W., Marsh, J.D. Circ. Res. (1985) [Pubmed]
  4. Effects of the calcium-channel agonist CGP 28392 on insulin secretion from isolated rat islets of Langerhans. Morgan, N.G., Short, C.D., Rumford, G.M., Montague, W. Biochem. J. (1985) [Pubmed]
  5. Agonists Bay-K8644 and CGP-28392 open calcium channels reconstituted from skeletal muscle transverse tubules. Affolter, H., Coronado, R. Biophys. J. (1985) [Pubmed]
  6. Calcium channels contribute to the decrease in blood pressure of pregnant rats. Simaan, M., Cadorette, C., Poterek, M., St-Louis, J., Brochu, M. Am. J. Physiol. Heart Circ. Physiol. (2002) [Pubmed]
  7. The influence of CGP 28392, a 1,4-dihydropyridine, on human platelet calcium and cyclic AMP metabolism. Resink, T.J., Erne, P., Bühler, F.R. Eur. J. Pharmacol. (1985) [Pubmed]
  8. Effects of a calcium entry promoting 1,4,5,7-tetrahydro-furo[3,4-b] pyridine derivative on Na+-, Ca2+- and Mg2+-dependent bioelectrical activity of Purkinje fibres and papillary muscles. Gerster, P., Riegger, C., Fallert, M. Arzneimittel-Forschung. (1987) [Pubmed]
  9. Comparative behavioral, neurochemical and pharmacological activities of dihydropyridine calcium channel activating drugs. O'Neill, S.K., McKay, D.W., Campbell, N., Triggle, C.R., Crowley, M., Bolger, G.T. J. Pharmacol. Exp. Ther. (1990) [Pubmed]
  10. Effect of calcium agonists, BAY K 8644 and CGP 28392, on guinea pig airway smooth muscle function during development. Pichoff, B.E., Uyehara, C.F., Nakamura, K.T. J. Pharmacol. Exp. Ther. (1993) [Pubmed]
  11. Stimulation rate modulates effects of the dihydropyridine CGP 28 392 on cardiac calcium-dependent action potentials. Kamp, T.J., Miller, R.J., Sanguinetti, M.C. Br. J. Pharmacol. (1985) [Pubmed]
  12. Effects of calcium channel activators BAY-K8644 and CGP-28392 on steroidogenesis in granulosa cells of the domestic hen. Asem, E.K., Tsang, B.K. Biochem. Biophys. Res. Commun. (1987) [Pubmed]
  13. Activation of the voltage-dependent Ca2+ channel in rat heart cells by dihydropyridine derivatives. Renaud, J.F., Méaux, J.P., Romey, G., Schmid, A., Lazdunski, M. Biochem. Biophys. Res. Commun. (1984) [Pubmed]
  14. Calcium mobilization, prostaglandin E2 and alpha 2-adrenoceptor modulation of glucose utilization and insulin secretion in pancreatic islets. Laychock, S.G., Bilgin, S. Biochem. Pharmacol. (1989) [Pubmed]
  15. In vitro comparative studies of the calcium-entry activators YC-170, CGP 28392, and BAY K 8644. Rogg, H., Criscione, L., Truog, A., Meier, M. J. Cardiovasc. Pharmacol. (1985) [Pubmed]
  16. Combined effects of a calcium-agonist and hypoglycemic or hyperglycemic sulfonamides upon insulin release. Malaisse, W.J., Sener, A., Malaisse-Lagae, F. Res. Commun. Chem. Pathol. Pharmacol. (1985) [Pubmed]
  17. Inhibitory effects of calcium channel agonists on renin release from rat kidney cortical slices. Matsumura, Y., Uriu, T., Shinyama, H., Sasaki, Y., Morimoto, S. J. Pharmacol. Exp. Ther. (1987) [Pubmed]
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