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Chemical Compound Review

Cpodpmb     3-cyclopentyloxy-N-(3,5- dichloropyridin-4...

Synonyms: Piclamilast, CHEMBL42126, SureCN26573, CCRIS 8304, CHEBI:47619, ...
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Disease relevance of Cpodpmb


High impact information on Cpodpmb


Biological context of Cpodpmb


Anatomical context of Cpodpmb

  • Only the highest dose of RP 73401 (400 micrograms kg-1) significantly inhibited eosinophil influx (41 +/- 16% inhibition) [10].
  • 1. We have investigated the inhibitory potency of RP 73401, a novel, highly selective and potent inhibitor of cyclic AMP-specific phosphodiesterase (PDE IV), against partially-purified PDE isoenzymes from smooth muscle and the particulate PDE IV from guinea-pig eosinophils [12].
  • 7. The results demonstrate that RP 73401 is a very potent inhibitor of TNF alpha release from human monocytes suggesting that it may have therapeutic potential in the many pathological conditions associated with over-production of this pro-inflammatory cytokine [7].
  • The fact that NCS 613 did not stimulate the gastric acid secretion suggests that this compound may produce fewer gastrointestinal side effects than second-generation PDE4 inhibitors, such as RP 73401 [13].
  • Finally, expressed CYP2B6 showed a high affinity (K(m) = 22.5 microM) for RP 73401 hydroxylation, similar to the human liver microsome studies [8].

Associations of Cpodpmb with other chemical compounds

  • 4. Local pretreatment with rolipram (40 microg cavity(-1)) or RP 73401 (40 microg cavity(-1)) 1 h before challenge reduced eosinophil accumulation evaluated in the rat pleural effluent, but only the former was active against eotaxin generation [14].
  • This concentration of siguazodan did not enhance the inhibitory action of RP 73401 on IL-2 release but potentiated its effect on DNA synthesis, increasing potency and efficacy [15].
  • In contrast, the PDE4 inhibitors RP 73401 and SB 207499 concentration-dependently suppressed IL-8 generation [16].
  • The rank order of potency of the various compounds for in vitro activities on arachidonic acid release is RP 73401 > NCS 613 > NCS 630 > NCS 632 > BWA 78U = NCS 631 [13].
  • Coumarin (10 microM), however, did not inhibit RP 73401 hydroxylation [8].

Gene context of Cpodpmb

  • RP 73401 (IC40: 0.011 +/- 0.004 microM) was a very potent inhibitor of anti-CD3-induced IL-4 release, being approximately 40-fold more potent than (+/-)-rolipram (IC40: 0.43 +/- 0.09 microM) [17].
  • The cGMP-inhibited PDE (PDE3) inhibitor, siguazodan, had little or no effect (IC40 > 100 microM) on anti-CD3-stimulated release of either IL-4 or IL-5 and did not significantly enhance the inhibitory action of RP 73401 on the release of either of these cytokines [17].
  • Of the 10 expressed P450 forms studied, only CYP2B6 catalyzed RP 73401 hydroxylation [8].
  • Piclamilast treatment dose-dependently and significantly prevented the increase in inflammatory cell number and goblet cell hyperplasia, as well as production of cytokines, including eotaxin, TNFalpha and IL-4 [3].
  • Liquid chromatography/mass spectrometry/mass spectrometry analysis of plasma from patients given RP 73401 also revealed a molecular ion and fragmentation consistent with RPR 113406 [8].

Analytical, diagnostic and therapeutic context of Cpodpmb


  1. Phosphodiesterase IV inhibition by piclamilast potentiates the cytodifferentiating action of retinoids in myeloid leukemia cells. Cross-talk between the cAMP and the retinoic acid signaling pathways. Parrella, E., Gianni', M., Cecconi, V., Nigro, E., Barzago, M.M., Rambaldi, A., Rochette-Egly, C., Terao, M., Garattini, E. J. Biol. Chem. (2004) [Pubmed]
  2. Effects of the phosphodiesterase 4 inhibitor RPR 73401 in a model of immunological inflammation. Ehinger, A.M., Gorr, G., Hoppmann, J., Telser, E., Ehinger, B., Kietzmann, M. Eur. J. Pharmacol. (2000) [Pubmed]
  3. Inhibition of phosphodiesterase activity, airway inflammation and hyperresponsiveness by PDE4 inhibitor and glucocorticoid in a murine model of allergic asthma. Sun, J.G., Deng, Y.M., Wu, X., Tang, H.F., Deng, J.F., Chen, J.Q., Yang, S.Y., Xie, Q.M. Life Sci. (2006) [Pubmed]
  4. Toxicologic and carcinogenic effects of the type IV phosphodiesterase inhibitor RP 73401 on the nasal olfactory tissue in rats. Pino, M.V., Valerio, M.G., Miller, G.K., Larson, J.L., Rosolia, D.L., Jayyosi, Z., Crouch, C.N., Trojanowski, J.Q., Geiger, L.E. Toxicologic pathology. (1999) [Pubmed]
  5. Inhibitor binding to type 4 phosphodiesterase (PDE4) assessed using [3H]piclamilast and [3H]rolipram. Zhao, Y., Zhang, H.T., O'Donnell, J.M. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  6. The selective phosphodiesterase 4 inhibitor RP 73-401 reduced matrix metalloproteinase 9 activity and transforming growth factor-beta release during acute lung injury in mice: the role of the balance between Tumor necrosis factor-alpha and interleukin-10. Corbel, M., Germain, N., Lanchou, J., Molet, S., R e Silva, P.M., Martins, M.A., Boichot, E., Lagente, V. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  7. Evidence that cyclic AMP phosphodiesterase inhibitors suppress TNF alpha generation from human monocytes by interacting with a 'low-affinity' phosphodiesterase 4 conformer. Souness, J.E., Griffin, M., Maslen, C., Ebsworth, K., Scott, L.C., Pollock, K., Palfreyman, M.N., Karlsson, J.A. Br. J. Pharmacol. (1996) [Pubmed]
  8. Human liver CYP2B6-catalyzed hydroxylation of RP 73401. Stevens, J.C., White, R.B., Hsu, S.H., Martinet, M. J. Pharmacol. Exp. Ther. (1997) [Pubmed]
  9. Structure-function analysis of human cytochrome P-450 2B6 using a novel substrate, site-directed mutagenesis, and molecular modeling. Domanski, T.L., Schultz, K.M., Roussel, F., Stevens, J.C., Halpert, J.R. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  10. Anti-inflammatory and bronchodilator properties of RP 73401, a novel and selective phosphodiesterase type IV inhibitor. Raeburn, D., Underwood, S.L., Lewis, S.A., Woodman, V.R., Battram, C.H., Tomkinson, A., Sharma, S., Jordan, R., Souness, J.E., Webber, S.E. Br. J. Pharmacol. (1994) [Pubmed]
  11. Comparison of recombinant human PDE4 isoforms: interaction with substrate and inhibitors. Saldou, N., Obernolte, R., Huber, A., Baecker, P.A., Wilhelm, R., Alvarez, R., Li, B., Xia, L., Callan, O., Su, C., Jarnagin, K., Shelton, E.R. Cell. Signal. (1998) [Pubmed]
  12. Suppression of eosinophil function by RP 73401, a potent and selective inhibitor of cyclic AMP-specific phosphodiesterase: comparison with rolipram. Souness, J.E., Maslen, C., Webber, S., Foster, M., Raeburn, D., Palfreyman, M.N., Ashton, M.J., Karlsson, J.A. Br. J. Pharmacol. (1995) [Pubmed]
  13. Anti-inflammatory activities of a new series of selective phosphodiesterase 4 inhibitors derived from 9-benzyladenine. Boichot, E., Wallace, J.L., Germain, N., Corbel, M., Lugnier, C., Lagente, V., Bourguignon, J.J. J. Pharmacol. Exp. Ther. (2000) [Pubmed]
  14. Modulation of eotaxin formation and eosinophil migration by selective inhibitors of phosphodiesterase type 4 isoenzyme. Silva, P.M., Alves, A.C., Serra, M.F., Pires, A.L., Silva, J.P., Barreto, E.O., Cordeiro, R.S., Jose, P.J., Teixeira, M.M., Lagente, V., Martins, M.A. Br. J. Pharmacol. (2001) [Pubmed]
  15. Evidence that cyclic AMP phosphodiesterase inhibitors suppress interleukin-2 release from murine splenocytes by interacting with a 'low-affinity' phosphodiesterase 4 conformer. Souness, J.E., Houghton, C., Sardar, N., Withnall, M.T. Br. J. Pharmacol. (1997) [Pubmed]
  16. Effect of PDE4 inhibitors on zymosan-induced IL-8 release from human neutrophils: synergism with prostanoids and salbutamol. Au, B.T., Teixeira, M.M., Collins, P.D., Williams, T.J. Br. J. Pharmacol. (1998) [Pubmed]
  17. Suppression of anti-CD3-induced interleukin-4 and interleukin-5 release from splenocytes of Mesocestoides corti-infected BALB/c mice by phosphodiesterase 4 inhibitors. Souness, J.E., Houghton, C., Sardar, N., Withnall, M.T. Biochem. Pharmacol. (1999) [Pubmed]
  18. Effect of food and gender on the pharmacokinetics of RP 73401, a phosphodiesterase IV inhibitor. Argenti, D., Vaccaro, S.K., Shah, B., Gillen, n.u.l.l., Rohatagi, S., Jensen, B.K. International journal of clinical pharmacology and therapeutics. (2000) [Pubmed]
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