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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

NIGULDIPINE     3-(4,4-diphenyl-1- piperidyl)propyl methyl...

Synonyms: Niguldipino, Niguldipinum, Dexniguldipine, Niguldipine(+), SureCN245993, ...
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Disease relevance of NIGULDIPINE

  • B859-35 had no effect on peripheral adenomas/adenocarcinomas, nasal cavity tumors, papillary polyps of larynx/trachea, or liver tumors induced by DEN under ambient air conditions [1].
  • In the hamster model, B859-35 had no antiproliferative effect on pulmonary adenomas of Clara cell origin [2].
  • The results of this study demonstrate that dexniguldipine has significant activity in the inhibition of canine osteosarcoma micrometastases [3].
  • Despite the lack of dose-limiting toxicity, higher doses of dexniguldipine do not appear to be useful for clinical evaluation because of the pharmacokinetic properties of the compound: therefore, 2,500 mg/day is recommended as the daily dose for phase II trials [4].
  • In this study, we have tested the hypothesis that dexniguldipine may inhibit the proliferation of lung cancer cells in response to autocrine or exogenous activation of PKC [5].

High impact information on NIGULDIPINE

  • On the other hand, a selective antiproliferative effect of the dihydropyridine derivative B859-35 on neuroendocrine lung tumor cells in vivo and in vitro suggests the potential use of such agents as cancer therapeutics [6].
  • The demonstrated inhibition of Ca2+/calmodulin and protein kinase C by B859-35 as reported in other in vitro systems suggests interference with such elements of signal transduction pathways as the molecular mechanism of the observed antiproliferative effects [6].
  • The studies revealed that 2.5 microM B859-35, a concentration equivalent to the IC50 in cell-free extracts, significantly depresses TPA-induced c-fosCAT expression [7].
  • It is demonstrated that B859-35 depresses the TPA-induced alkalinization with an IC50 of 5 microM, indicating that PKC in intact cells and the enzyme in cell-free extracts are equally sensitive to the drug [7].
  • At 1 microM phosphatidylserine, half-maximal inhibition (IC50) is obtained at approximately 2.5 microM B859-35 [7].

Chemical compound and disease context of NIGULDIPINE


Biological context of NIGULDIPINE


Anatomical context of NIGULDIPINE

  • B859-35 was a potent antiproliferative agent in the neuroendocrine line NCI-H727 at concentrations as low as 0.001 pM, while it inhibited cell proliferation in the two other cell lines at concentrations of 100 nM and above [2].
  • Studies in NIH 3T3 fibroblasts have provided evidence that dexniguldipine may also inhibit protein kinase C (PKC) [5].

Associations of NIGULDIPINE with other chemical compounds


Gene context of NIGULDIPINE


Analytical, diagnostic and therapeutic context of NIGULDIPINE

  • The MS results, corroborated by MALDI-MS of peptides after one step of Edman analysis, identified the radioactive 7-kDa band as the dexniguldipine-bound, tryptic P-gp peptide, 468-527 [9].
  • Dexniguldipine 40 mg/kg intraperitoneally (i.p.) given once 4 h before VCR 1 mg/kg intravenously (i.v.) resulted in increased VCR concentrations in BRO/mdr1.1 xenograft tissue [11].
  • Two-dimensional high-performance liquid chromatography at low ng/ml levels of the anti-proliferative agent B859-35 in serum with automated sample clean-up, solid-phase trapping and ultraviolet detection [18].
  • Amputation and dexniguldipine as treatment for canine appendicular osteosarcoma [3].


  1. Successful chemotherapy of experimental neuroendocrine lung tumors in hamsters with an antagonist of Ca2+/calmodulin. Schuller, H.M., Correa, E., Orloff, M., Reznik, G.K. Cancer Res. (1990) [Pubmed]
  2. Antiproliferative effects of the Ca2+/calmodulin antagonist B859-35 and the Ca(2+)-channel blocker verapamil on human lung cancer cell lines. Schüller, H.M., Orloff, M., Reznik, G.K. Carcinogenesis (1991) [Pubmed]
  3. Amputation and dexniguldipine as treatment for canine appendicular osteosarcoma. Hahn, K.A., Legendre, A.M., Schuller, H.M. J. Cancer Res. Clin. Oncol. (1997) [Pubmed]
  4. Tolerance, safety, and kinetics of the new antineoplastic compound dexniguldipine-HCl after oral administration: a phase I dose-escalation trial. Ukena, D., Boewer, C., Oldenkott, B., Rathgeb, F., Wurst, W., Zech, K., Sybrecht, G.W. Cancer Chemother. Pharmacol. (1995) [Pubmed]
  5. Inhibition of protein-kinase-C--dependent cell proliferation of human lung cancer cell lines by the dihydropyridine dexniguldipine. Schuller, H.M., Orloff, M., Reznik, G.K. J. Cancer Res. Clin. Oncol. (1994) [Pubmed]
  6. Nitrosamine-induced lung carcinogenesis and Ca2+/calmodulin antagonists. Schüller, H.M. Cancer Res. (1992) [Pubmed]
  7. Inhibition of cell proliferation, protein kinase C, and phorbol ester-induced fos expression by the dihydropyridine derivative B859-35. Uberall, F., Maly, K., Egle, A., Doppler, W., Hofmann, J., Grunicke, H.H. Cancer Res. (1991) [Pubmed]
  8. Modulation of multidrug resistance by BIBW22BS in blasts of de novo or relapsed or persistent acute myeloid leukemia ex vivo. Schröder, J., Esteban, M., Müller, M.R., Kasimir-Bauer, S., Bamberger, U., Heckel, A., Seeber, S., Scheulen, M.E. J. Cancer Res. Clin. Oncol. (1996) [Pubmed]
  9. Characterization of the dexniguldipine binding site in the multidrug resistance-related transport protein P-glycoprotein by photoaffinity labeling and mass spectrometry. Borchers, C., Boer, R., Klemm, K., Figala, V., Denzinger, T., Ulrich, W.R., Haas, S., Ise, W., Gekeler, V., Przybylski, M. Mol. Pharmacol. (2002) [Pubmed]
  10. B-859-35, a new drug with anti-tumor activity reverses multi-drug resistance. Hofmann, J., Ueberall, F., Egle, A., Grunicke, H. Int. J. Cancer (1991) [Pubmed]
  11. The influence of P170-glycoprotein modulators on the efficacy and the distribution of vincristine as well as on MDR1 expression in BRO/mdr1.1 human melanoma xenografts. Boven, E., Jansen, W.J., Hulscher, T.M., Beijnen, J.H., van Tellingen, O. Eur. J. Cancer (1999) [Pubmed]
  12. Resistance to the new anti-cancer phospholipid ilmofosine (BM 41 440). Hofmann, J., Utz, I., Spitaler, M., Hofer, S., Rybczynska, M., Beck, W.T., Herrmann, D.B., Grunicke, H. Br. J. Cancer (1997) [Pubmed]
  13. Secondary combined resistance to the multidrug-resistance-reversing activity of cyclosporin A in the cell line F4-6RADR-CsA. Dietel, M., Herzig, I., Reymann, A., Brandt, I., Schaefer, B., Bunge, A., Heidebrecht, H.J., Seidel, A. J. Cancer Res. Clin. Oncol. (1994) [Pubmed]
  14. Pharmacokinetics of the multidrug-resistance-converting drug dexniguldipine and its pyridine metabolite M-1 in the plasma, tumor, and renal tissue of tumor-bearing Wag/Rij rats. Schellens, J.H., Van de Vrie, W., Loos, W.J., Kolker, H.J., Verweij, J., Stoter, G., Durante, N.M., Eggermont, A.M. Cancer Chemother. Pharmacol. (1997) [Pubmed]
  15. Modulation of multidrug resistance with dexniguldipine hydrochloride (B8509-035) in the CC531 rat colon carcinoma model. Van de Vrie, W., Schellens, J.H., Loss, W.J., Kolker, H.J., Verwey, J., Stoter, G., Durante, N.M., Eggermont, A.M. J. Cancer Res. Clin. Oncol. (1996) [Pubmed]
  16. Clinical importance of P-glycoprotein-related resistance in leukemia and myelodysplastic syndromes--first experience with their reversal. Nüssler, V., Pelka-Fleischer, R., Zwierzina, H., Nerl, C., Beckert, B., Gullis, E., Gieseler, F., Bock, S., Bartl, R., Petrides, P.E. Ann. Hematol. (1994) [Pubmed]
  17. Allosteric regulation of [3H]vinblastine binding to P-glycoprotein of MCF-7 ADR cells by dexniguldipine. Ferry, D.R., Malkhandi, P.J., Russell, M.A., Kerr, D.J. Biochem. Pharmacol. (1995) [Pubmed]
  18. Two-dimensional high-performance liquid chromatography at low ng/ml levels of the anti-proliferative agent B859-35 in serum with automated sample clean-up, solid-phase trapping and ultraviolet detection. Zech, K., Herzog, R. J. Chromatogr. (1991) [Pubmed]
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