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2008
28 August 2008: Announcement no. 2, 2008: Zealand Pharma today announced that Dr. David H...
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Product Pipeline
Zealand's Pipeline comprises 1 compound in phase III, 2 compounds in phase II, 3 compounds ...
Rotigaptide/ZP123 Publications
Lin, X., Zemlin, C., Hennan, J.K., Petersen, J.S. and Veenstra, R.D.:
Enhancementof ventricular gap-junction coupling by rotigaptide.
Cardiovascular Research (2008) 79, 416–426
Kjølbye, A.L., Dikshteyn, M., Eloff, B.C., Deschênes, I., and Rosenbaum, D.S.: Maintenance of intercellular coupling by the antiarrhythmic peptide rotigaptide suppresses arrhythmogenic discordant alternans.
Am J Physiol Heart Circ Physiol 2008, 294, H41–H49
Kjølbye, A.L.:
Rotigaptide: From Drug Discovery to Clinical Application
Presentation at The American Heart Association Meeting and Scientific Sessions 2007, Orlando, Florida, USA, Nov. 3-7, 2007.
Kjølbye, A. L., Haugan, K., Hennan, J. K. and Petersen, J. S.:
Pharmacological Modulation of Gap Junction Function with the Novel Compound Rotigaptide: A Promising New Principle for Prevention of Arrhythmias
Basic & Clinical Pharmacology & Toxicology, 2007, 101, 215–230
Axelsen, L.N., Haugan, K., Stahlhut, M., Kjølbye, A.-L., Hennan, J.K., Holstein-Rathlou, N.-H., Petersen, J.S., Nielsen, M.S.:
Increasing gap junctional coupling. A tool for dissecting the role of gap junctions.
J Membr Biol, 2007, 216, 23-35
Haugan, K. and Petersen, J.S.:
Gap junction modifying antiarrhythmic peptides: Therapeutic potential in atrial fibrillation.
Drugs of the Future, 2007, 32, 245-260
Shiroshita-Takeshita, A., Sakabe, M., Haugan, K., Hennan, J.K. and Nattel, S.:
Model-dependent effect of the Gap Junction conducting-enhancing antiarrhythmic peptide Rotigaptide (ZP123) on experimental atrial fibrillation in dogs.
Circulation 2007, 115, 310-318
Shiroshita-Takeshita, A., Sakabe, M., Haugan, K., Hennan, J.K., and Nattel, S.: Model-dependent Effects of a Gap Junction Conduction Enhancing Antiarrhythmic Peptide (Rotigaptide) in Experimental Atrial Fibrillation.
Abstract for Heart Rhythm Society 27th Annual Scientific Sessions, May 17-20, 2006, Boston
Heart Rhytm, 2006, 3, No 5, May Supplement S96, Abstract AB46-4
Udata, C., Micalizzi, M., Katz, A., M Giorgio, Q. and Meng, X.:
Ascending Single Dose Study of the Safety, Tolerability, and Pharmacokinetics of Rotigaptide (ZP123) Administered Intravenously to Healthy Subjects.
Poster presentation at The 2006 American Society for Clinical Pharmacology and Therapeutics (ASCPT) Annual Meeting, Baltimore, Maryland, USA. March 7-11, 2006.
Clin Pharmacol Ther, 2006, 79, P77, Abstract PIII-70
Udata, C., Micalizzi, M., Katz, A., Giorgio, Q.M., and Meng, X.:
Six-Day Continuous IV Infusion Study of the Safety, Tolerability, and PK of Ascending Doses of Rotagaptide (ZP123) in Healthy Subjects.
Poster presentation at The 2006 American Society for Clinical Pharmacology and Therapeutics (ASCPT) Annual Meeting, Baltimore, Maryland, USA. March 7-11, 2006.
Clin Pharmacol Ther, 2006, 79, P50, Abstract PII-53
Udata, C., Parks, V., Patat, A., Fauchoux, N. and Meng, X.:
Absence of Drug Interaction Between Rotigaptide (ZP123) and Digoxin.
Poster presentation at The 2006 American Society for Clinical Pharmacology and Therapeutics (ASCPT) Annual Meeting, Baltimore, Maryland, USA. March 7-11, 2006.
Clin Pharmacol Ther, 2006, 79, P25, Abstract PI-71
Nattel, S and Carlsson, L.
Innovative approaches to anti-arrhythmic drug therapy.
Nature Reviews Drug Discovery 2006, 5, 1034-1049
Haugan H., Miyamoto, T., Takeishi, Y., Kubota, I., Nakayama, J., Shimojo, H., and Hirose, M.:
Rotigaptide (ZP123) improves atrial conduction slowing in chronic volume overload-induced dilated atria.
Basic Clin. Pharmacol. Toxicol. 2006, 99, 71-79
Guerra, J.M., Everett, T.H., Lee, K.W., Wilson, E. and Olgin, J.E.:
Effects of the Gap Junction Modifier Rotigaptide (ZP123) on Atrial Conduction and Vulnerability to Atrial Fibrillation.
Circulation 2006, 114, 110-118
Axelsen, L.N., Stahlhut, M., Mohammed, S., Larsen, B.D., Nielsen, M.S., Holstein-Rathlou, N.-H., Andersen, S., Jensen, O.N., Hennan, J.K. and Kjølbye, A.L.:
Identification of ischemia-regulated phosphorylation sites in connexin43: A possible target for the antiarrhythmic peptide analogue rotigaptide (ZP123).
Journal of Molecular and Cellular Cardiology, 2006, 40, 790–798
Stahlhut, M., Petersen, J.S., Hennan, J.K. and Ramirez, M.T.:
The Antiarrhythmic Peptide Rotigaptide (ZP123) Increases Connexin 43 Protein Expression in Neonatal Rat Ventricular Cardiomyocytes
Cell Communication and Adhesion 2006, 13, 21–27
Hennan, J.K., Swillo, R.E., Morgan, G.A., Keith, J.C., Schaub, R.G., Smith, R.P., Feldman, H.S., Haugan, K., Kantrowitz, J., Wang, P.J., Abu-Qare, A., Butera, J., Larsen, B.D. and Crandall, D.L.:
Rotigaptide (ZP123) Prevents Spontaneous Ventricular Arrhythmias and Reduces Infarct Size During Myocardial Ischemia/Reperfusion Injury in Open-Chest Dogs.
J Pharm Exp Ther, 2006, 317, 236–243
Clarke, T.C., Thomas, D., Petersen, J.S., Evans, W.H., and Martin, P.E.M.:
The antiarrhythmic peptide rotigaptide (ZP123) increases gap junction intercellular communication in cardiac myocytes and HeLa cells expressing connexin 43.
Br. J. Pharmacol. 2006, 147, 486–495
Haugan, K., Marcussen, N., Kjølbye, A.L.; Nielsen, M.S.; Hennan, J.K. and Petersen, J.S.:
Treatment With The Gap Junction Modifier Rotigaptide (ZP123) Reduces Infarct Size In Rats With Chronic Myocardial Infarction.
J Cardiovasc Pharmacol, 2006, 47, 236–242
Hennan, J.K., Swillo, R.E., Morgan, G.A., Keith, J.C., Schaub, R.G., Smith, R.P., Feldman, H.S., Haugan, K., Kantrowitz, J, Wang, P.J., Abu-Qare, A., Butera, J., Larsen, B.D. and Crandall, D.L.:
Rotigaptide (ZP123) Prevents Spontaneous Ventricular Arrhythmias And Reduces Infarct Size During Myocardial Ischemia/Reperfusion Injury In Open-Chest Dogs.
Published on December 12, 2005 as JPET Fast Forward, DOI:10.1124/jpet.105.096933
Haugan, K., Kjølbye, A.L., Hennan, J.K., and Petersen, J.S.:
Rotigaptide (ZP123) reverts established atrial conduction velocity slowing.
Cell Comm. Adhes. 2005, 12, 271–278
Editorial
Molecule of the month: Rotigaptide.
Drug News Perspect 18(9), November 2005
Hennan, J.K., Feldman, H.S., Swillo, R.E., Morgan, G.A., Keith Jr, J.C., Schaub, R.G., Smith, R.P., Haugan, K., Kantrowitz, J., Butera, J., and Crandall, D.L.:
ZP123 Prevents Spontaneous Arrhythmias and Reduces Infarct Size During Myocardial Ischemia/Reperfusion Injury in Open-Chest Dogs.
Poster at American Heart Association. Scientific Sessions 2005, November 13-16, 2005, Dallas, Texas, USA
Circulation, 2005, 112, No 17, II-16, Abstract No. 170
Axelsen, L.N., Mohammed, S., Kjølbye, A.L., Nielsen, M.S., Holstein-Rathlou, N.-H., Jensen, O.N., Andersen, S., Hennan, J.K., Stahlhut, M.:
Serine 297 and Serine 306: Two New Phosphorylation Sites Involved in the Regulation of Connexin43 during Ischemia.
Presentation at American Heart Association. Scientific Sessions 2005, November 13-16, 2005, Dallas, Texas, USA
Circulation, 2005, 112, No 17, II-114, Abstract No. 635
Dorian, P., Zhong, J., Hu, X., So, P.S.-S., Debicki, D., and Hennan, J.K.:
Increasing Gap Junction Conductance with ZP123 Improves Defibrillation Success in Experimental Cardiac Arrest.
Abstract submitted for American Heart Association. Scientific Sessions 2005, November 13-16, 2005, Dallas, Texas, USA
Circulation, 2005, 112, No 17, II-115, Abstract No. 637
Haugan, K., Miyamoto, T., Takeishi, Y., Kubota, I., Nakayama, J., and Hirose, M.:
ZP123 improves atrial conduction slowing in chronic volume overload-induced dilated atria.
Abstract for European Society of Cardiology, Stockholm, Sept 2005
Eur Heart J, 2005, 26 (Suppl. 1), 511
Poster presentation
Jørgensen, N.R., Teilmann, S.C., Henriksen, Z, Meier, E., Hansen, S.S., Jensen, J.-E., Sørensen, O.H., and Petersen, J.S.:
The Antiarrhythmic Peptide Analog Rotigaptide (ZP123) Stimulates Gap Junction Intercellular Communication in Human Osteoblasts and Prevents Decrease in Femoral Trabecular Bone Strength in Ovariectomized Rats.
Endocrinology 2005, 146, 4745–4754
Stahlhut, M., Petersen, J.S., Hennan, J., and Ramirez, M.T.:
The anti-arrhythmic, gap junction modulator peptide ZP123 increases connexin 43 expression in neonatal rat cardiomyocytes by affecting protein turnover.
Poster 135 at The 2005 International Gap Junction Conference. August 13-18, Whistler, British Columbia, Canada. Abstract book p 223.
Poster Presentation
Martin, P.E.M., Clarke, T.C, Easton, J.A., Petersen, J.S., and Evans, W.H.:
The Antiarrhythmic Peptide ZP123 Increases Gap Junction Intercellular Communication in Cardiac Myocytes, Atrial HL-1 Cells, and Hela Cells Expressing Cx43.
Poster 93 at The 2005 International Gap Junction Conference. August 13-18, Whistler, British Columbia, Canada. Abstract book p 181.
Poster Presentation
Hennan, J.K., Swillo, R.E., Morgan, G.A., Haugan, and Crandall, D.L.:
ZP123 Prevents Spontaneous Arrhythmias and Reduces Infarct Size During Myocardial Ischemia/Reperfusion Injury in Open-Chest Dogs.
Poster 52 at The 2005 International Gap Junction Conference. August 13-18, Whistler, British Columbia, Canada. Abstract book p 140.
Poster Presentation
Haugan, K., Olsen, K.B., Petersen, J.S., Holstein-Rathlou, N.-H., Hennan, J.K., and Nielsen, M.S.:
The Antiarrhythmic Peptide Analogue ZP123 Prevents and Reverts Atrial Conduction Slowing During Metabolic Stress.
Oral presentation at The 2005 International Gap Junction Conference. August 13-18, Whistler, British Columbia, Canada. Abstract book p 58.
Presentation
Axelsen, L.N., Mohammed, S., Kjølbye, A.L., Nielsen, M.S., Holstein-Rathlou, N.-H., Jensen, O.N., Andersen, S. Hennan, J.K., and Stahlhut, M.:
Characterization of connexin 43 phosphorylation during ischemia. Effect of the antiarrhythmic peptide analogue ZP123.
Oral presentation at The 2005 International Gap Junction Conference. August 13-18, Whistler, British Columbia, Canada. Abstract book p 31
Presentation
Axelsen, L.N., Mohammed, S., Kjølbye, A.L., Nielsen, M.S., Holstein-Rathlou, N.-H., Jensen, O.N., Andersen, S. Hennan, J.K., and Stahlhut, M.:
Characterization of connexin 43 phosphorylation during ischemia. Effect of the antiarrhythmic peptide analogue ZP123.
Presentation at DACRA´s 2005 Summer Meeting at The Sandbjerg Estate, 9-11 June 2005 ; abstract No. 2.
Haugan, K., Olsen, K.B., Hartvig, L., Petersen, J.S., Holstein-Rathlou, N.-H., Hennan, J.K. and Nielsen, M.S.:
The Antiarrhythmic Peptide Analogue ZP123 Prevents and Reverts Atrial Conduction Slowing During Metabolic Stress.
Presentation at DACRA´s 2005 Summer Meeting at The Sandbjerg Estate, 9-11 June 2005 ; abstract No. 6.
Guerra, J.M., Everett, T.H., Lee, K.W., Hennan, J., Wilson, E., and Olgin, J.E.:
Enhancement of cell coupling reduces AF vulnerability in a canine model of chronic mitral regulation.
Abstract from 26th Annual Scientific Sessions of Heart Rhythm Society, May 4-7, 2005, New Orleans, Louisiana, USA.
Heart Rhythm, 2005, 2, No. 5, May Supplement, S96-S97
Haugan, K., Olsen, K.B., Hartvig, L., Petersen, J.S., Holstein-Rathlou, N.-H., Hennan, J.K. and Nielsen, M.S.:
The Antiarrhythmic Peptide Analogue ZP123 Prevents Atrial Conduction Slowing during Metabolic Stress.
J. Cardiovasc. Electrophysiol. 2005, 16, 537-545
Xing, D., Kjølbye, A.L., Petersen, J.S. and Martins, J.B.:
Pharmacological stimulation of cardiac gap junction coupling does not affect ischemia-induced focal ventricular tachycardia or triggered activity in dogs.
Am. J. Physiol. Heart Circ. Physiol. 2005, 288, H511-H516
Haugan, K., Olsen, K.B., Hartvig, L., Petersen, J.S., Holstein-Rathlou, N.-H., Hennan, J.K. and Nielsen, M.S.:
The antiarrhythmic peptide analogue ZP123 prevents atrial conduction slowing during metabolic stress.
Poster B4 for Dansk Farmakologi 2005, 19 Januar, 2005, SDU, Odense, Denmark, Abstract
Poster presentation
Hartvig, L., Christjansen, K.N., Hyttel, J. and Petersen, J.S.:
ZP123 prevents 18a-glycyrrhetinic acid-induced inhibition of cAMP transfer.
PhysPharm 2003; Scandinavian Congress of Physiology and Pharmacology, Odense, Denmark, 11-14 October 2003.
Acta Physiol Scand, 2004, 181, A109, Abstract P 07-07
Poster presentation
Eloff, B.C., Gilat, E., Wan, X., and Rosenbaum, D.S.:
Pharmacological Modulation of Cardiac Gap Junctions to Enhance Cardiac Conduction: Evidence Supporting a Novel Target for Antiarrhythmic Therapy.
Circulation, Dec 2003; 108: 3157 - 3163
Dhein, S., Larsen, B.D., Petersen, J.S., Mohr, F-W.:
Effects of the new antiarrhythmic peptide ZP123 on epicardial activation and repolarization pattern.
Cell Communication and Adhesion 2003. Vol. 10, pp 371-378
Kjølbye, A.L., Eloff, B.C. and Rosenbaum, D.S.:
Maintenance of intercellular coupling by ZP123 suppresses arrhythmogenic discordant alternans.
American Heart Association, Scientific Sessions 2003 9-12 Nov. 2003, Orlando, Florida, USA.
Circulation 2003, 108 (supplement IV), Abstract 1389, p IV-292
Power Point Presentation
Dhein, S., Larsen B.D. and Petersen J.S.:
Effects of the New antiarrhythmic peptide ZP123 on epicardial activation and repolarisation.
2003 International Gap Junction Conference, August 23-28, 2003, Cambridge, UK. Poster abstract p. 58
Hartvig, L., Christjansen, K.N., Hyttel, J. and Petersen, J.S.:
ZP123 prevents 18a-glycyrrhetinic acid-induced inhibition of cAMP transfer.
2003 International Gap Junction Conference, August 23-28, 2003, Cambridge, UK. Poster abstract p. 70
Poster presentation
Haugan, K., Petersen, J.S., Hartvig, L., Holstein-Rathlou, N-H. and Nielsen, M.S.:
The antiarrhythmic peptide analogue ZP123 inhibits acidosis-induced decrease in atrial conduction velocity in isolated left rat atrium.
2003 International Gap Junction Conference, August 23-28, 2003, Cambridge, UK. Poster abstract p. 70
Poster presentation
Nielsen, M.S., Marcussen, N., Jørgensen, N.K., Holstein-Rathlou, N-H., Kjølbye, A.L. and Petersen, J.S.:
ZP123 inhibits ischemia-induced cell swelling in cardiomyocytes and reduces infarct size after myocardial infarction (MI) in rats.
2003 International Gap Junction Conference, August 23-28, 2003, Cambridge, UK. Poster abstract p. 109
Kjølbye, A.L., Knudsen, C.B., Jepsen, T., Larsen, B.D. and Petersen, J.S.:
Pharmacological characterization of the new stable antiarrhythmic peptide analog Ac-D-Tyr-D-Pro-D-Hyp-Gly-D-Ala-Gly-NH2 (ZP123): In vivo and in vitro studies.
J. Pharmacol. Exp. Ther., 2003. 306, 1191-1199
Xing, D., Kjølbye, A. L., Nielsen. M.S., Petersen, J. S., Harlow, K. W., Holstein-Rathlou, N.-H. and Martins, J. B.:
ZP123 Increases Gap Junctional Conductance and Prevents Reentrant Ventricular Tachycardia During Myocardial Ischemia in Open Chest Dogs.
J. Cardiovasc. Electrophysiol. 2003. 14, 510-520.
Hansen, S. S., Henriksen, Z., Petersen, J. S., Sørensen, O. H., and Jørgensen, N. R.:
The AAP analogue ZP123 increases intercellular coupling in human osteoblasts and stimulates production of bone formation markers in vitro.
30th European Symposium on Calcified Tissues, Rome, Italy, 8-12 May, 2003, Poster abstract, No. P-93, p 358
Eloff, B. C., Gilat, E. and Rosenbaum, D. S.:
Gap Junction Modifier ZP123 Inhibits Acidosis-Induced Conduction Slowing
Poster at American Heart Association Scientific Sessions 2002, Chicago, USA, November 17-20, 2002.
Circulation, 2002, 106, No. 19 (Suppl. II), p II-87, Abstract 440
Kjølbye, A.L., Holstein-Rathlou, N.-H. and Petersen, J.S.:
Anti-arrhythmic Peptide N-3-(4-Hydroxyphenyl)propionyl-Pro-Hyp-Gly-Ala-Gly-OH Reduces Dispersion of Action Potential Duration During Ischemia/Reperfusion in Rabbit Hearts.
J. Cardiovasc. Pharmacol. 2002. 40, 770–779
Xing, D., Kjølbye, A. L., Petersen, J. S., Harlow, K. and Martins, J. B.:
The novel gap junction opener ZP123 prevents reentrant ventricular tachycardia during ischemia in open-chest dogs.
American Heart Association Scientific Sessions 2001, Anaheim, CA, U.S.A., November 11-14, 2001.
Circulation 2001, 104 (17) (Supplement II), II-46, Abstract 223.
Poster presentation
Petersen, J. S, Kjølbye, A-L., Larsen, B. D., Harlow, K. W., Jepsen, T., Meier E., Vinge, M. M., Nielsen, M. S., Holstein-Rathlou, N-H., Xing, D., Martins, J. B, Teilmann, S. C., Sørensen, O. H., Jørgensen, N. R.:
Antiarrhythmic effects of the gap junction opener ZP123
Meeting of the Scandinavian Physiological Society: “Pumps, channels and their physiological significance”, University of Aarhus, Denmark
October 26-28, 2001
Acta Physiol. Scand. 2002, 174, pp. A171-A172
Petersen, J. S. and Kjølbye, A. L.:
The gap junction openers ZS42-0123 and AAP10 prevent calcium-induced AV-block and ventricular fibrillation (VF) in mice.
International Gap Junction Conference, August 4-9, 2001, Honolulu, Hawaii, USA, Abstract p 154.
Poster presentation
Kjølbye, A. L. and Petersen, J. S.:
The gap junction opener ZS42-0123 reduces epicardial monophasic action potential (MAP) heterogeneity during hypokalemic ischemia in isolated rabbit hearts.
2001 International Gap Junction Conference, August 4-9, 2001, Honolulu, Hawaii, USA, Abstract p 99
Poster presentation
Beck, M. M. and Meier, E.:
ZS42-0123 enhances norepinephrine (NE) - induced phosphoinositol (PI) turnover in cultured cardiomyocytes during metabolic stress.
2001 International Gap Junction Conference, August 4-9, 2001, Honolulu, Hawaii, USA, Abstract p 132
Poster presentation
Nielsen, M. S., Petersen, J. S., Meier, E. and Holstein-Rathlou, N.-H.:
ZS42-0123 increases cardiac gap junction intercellular communication (GJIC) by an AAP receptor-mediated mechanism.
2001 International Gap Junction Conference, August 4-9, 2001, Honolulu, Hawaii, USA, Abstract p 145
Poster presentation
Teilmann, S. C., Henriksen, Z., Meier, E., Petersen, J. S., Sørensen, O.H., and Jørgensen, N. R.:
The gap junction opener ZS42-0123 enhances intercellular communication in osteoblastic cells.
2001 International Gap Junction Conference, August 4-9, 2001, Honolulu, Hawaii, USA, Abstract p 176
Poster presentation
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