APEPTICO - Innovation in peptide drugs

Publications

Romero MJ, Yue Q, Singla B, Hamacher J, Sridhar S, Moseley AS, Song C, Mraheil MA, Fischer B, Zeitlinger M, Chakraborty T, Fulton D, Gan L, Annex BH, Csanyi G, Eaton DC, Rudolf Lucas. Direct endothelial ENaC activation mitigates vasculopathy induced by SARS-CoV2 spike protein. Front. Immunol. 14:1241448 (2023) doi: 10.3389/fimmu.2023.1241448.

Pinto ACMD, de Melo Nunes R, Nogueira IA, Fischer B, Lucas R, Girão-Carmona VCC, de Oliveira VLS, Amaral FA, Schett G, Rocha FAC. Potent anti-inflammatory activity of the lectin-like domain of TNF in joints. Front. Immunol., 31 October 2022 (https://doi.org/10.3389/fimmu.2022.1049368).

Martin-Malpartida P, Arrastia-Casado S, Farrera-Sinfreu J, Lucas R, Fischer H, Fischer B, Eaton DC, Tzotzos S, Macias MJ. Conformational ensemble of the TNF-derived peptide solnatide in solution. Computational and Structural Biotechnology Journal 20 (2022) 2082–2090.

Schmid B, Kranke P, Lucas R, Meybohm P, Zwissler B, Frank S. sequential multiple ascending doses of solnatide to treat pulmonary permeability edema in patients with moderate to severe ARDS in a randomized, placebo-controlled, double-blind trial: preliminary evaluation of safety and feasibility in light of the COVID- 19 pandemic. Trials (2022) 23:252.

Schmid B, Kredel M, Ullrich R, Krenn K, Lucas R, Markstaller K, Fischer B, Kranke P, Meybohm P, Zwißler B, Frank S.  Safety and preliminary efficacy of sequential multiple ascending doses of solnatide to treat pulmonary permeability edema in patients with moderate-to-severe ARDS—a randomized, placebo-controlled, double-blind trial. Trials (2021) 22:643.

Tzotzos S, Fischer B, Fischer H, Zeitlinger M. Incidence of ARDS and outcomes in hospitalised patients with COVID-19: a global literature survey. Critical Care. Critical Care (2020) 24:516 https://doi.org/10.1186/s13054-020-03240-7.

Aigner C, Slama A, Barta M, Mitterbauer A, lang G, Taghavi S, Matilla J, Ullrich R, Krenn K, Jaksch P, Markstaller K, Klepetko W. Treatment of primary graft dysfunction after lung transplantation with orally inhaled AP301: a prospective, randomized pilot study. J Heart Lung Transplant 2017 Sep 30.

Krenn K, Lucas R, Croize A, Boehme S, Klein KU, Hermann R, Markstaller K, Ullrich R. Inhaled AP301 for treatment of pulmonary edema in mechanically ventilated patients with acute respiratory distress syndrome: a phase IIa randomized placebo-controlled trial. Crit Care 2017; 21(1):194.

Willam A, Aufy M, Tzotzos S, El-Malazi D, Poser F, Wagner A, Unterköfler B, Gurmani D, Martan D, Iqbal SM, Fischer B, Fischer H, Pietschmann H, Czikora I, Lucas R, Lemmens-Gruber R, Shabbir W. TNF lectin-like domain restores epithelial sodium channel function in frameshift mutants associated with pseudohypoaldosteronism type 1B. Front Immunol 2017; 8:601.

Zhou Q, Wang D, Liu Y, Yang X, Lucas R, Fischer B. Solnatide demonstrates profound therapeutic activity in a rat model of pulmonary edema induced by acute hypobaric hypoxia and exercise. Chest 2017; 151(3):658-667.

Willam A, Aufy M, Tzotzos S, Evanzin H, Chytracek S, Geppert S, Fischer B, Fischer H, Pietschmann H, Czikora I, Lucas R, Lemmens-Gruber R, Shabbir W. Restoration of epithelial sodium channel function by synthetic peptides in pseudohypoaldosteronism type 1B mutants. Front Pharmacol 2017; 8:85.

Lucas R, Yue Q, Alli A, Duke BJ, Al-Khalili O, Thai TL, Hamacher J, Sridhar S, Lebedyeva I, Su H, Tzotzos S, Fischer B, Gameiro AF, Loose M, Chakraborty T, Shabbir W, Aufy M, Lemmens-Gruber R, Eaton DC, Czikora I. The lectin-like domain of TNF increases ENaC open probability through a novel site at the interface between the second transmembrane and C-terminal domains of the alpha-subunit. J Biol Chem 2016; 291(45):23440-23451.

Shabbir W, Tzotzos S, Bedak M, Aufy M, Willam A, Kraihammer M, Holzner A, Czikora I, Scherbaum-Hazemi P, Fischer H, Pietschmann H, Fischer B, Lucas R, Lemmens-Gruber R. Glycosylation-dependent activation of epithelial sodium channel by solnatide. Biochem Pharmacol 2015; 98(4):740-53.

Sieck GC and Wylam ME. Editorial: Paradoxical Use of Tumor Necrosis Factor in Treating Pulmonary Edema. Am J Respir Crit Care Med Vol 190, Iss 6, pp 595-605, Sep 15, 2014.

Czikora I, Alli A, Bao H-F, Kaftan D, Sridhar S, Apell H-J, Gorshkov B, White R, Zimmermann A, Wendel A, et al. A novel tumor necrosis factor-mediated mechanism of direct epithelial sodium channel activation. Am J Respir Crit Care Med 2014;190:522-532.

Krenn K, Croize A, Klein KU, Bohme S, Markstaller K, Ullrich R, Hermann R, Lucas R, Fischer B. Oral inhalation of AP301 peptide activates pulmonary oedema clearance: initial results from a phase IIa clinical trial in mechanically ventilated ICU patients. Presented at the ERS International Congress 2014. September 6-10, Munich, Germany.

Hartmann EK, Thomas R, Liu T, Stefaniak J, Ziebart A, Duenges B, Eckle D, Markstaller K, David M. TIP peptide inhalation in experimental acute lung injury: effect of repetitive dosage and different synthetic variants. BMC Anesthesiol 2014;14:42.

Schwameis R, Eder S, Pietschmann H, Fischer B, Mascher H, Tzotzos S, Fischer H, Lucas R, Zeitlinger M, Hermann R. A FIM Study to Assess Safety and Exposure of Inhaled Single Doses of AP301 - a Specific ENaC Channel Activator for the Treatment of Acute Lung Injury. J Clin Pharmacol. 2014 Mar;54(3):341-50. doi:10.1002/jcph.203. PubMed PMID: 24515273.

Shabbir W, Scherbaum-Hazemi P, Tzotzos S, Fischer B, Fischer H, Pietschmann H, Lucas R, Lemmens-Gruber R. Mechanism of Action of Novel Lung Edema Therapeutic AP301 by Activation of the Epithelial Sodium Channel. Mol Pharmacol. 2013 Dec;84(6):899-910. doi: 10.1124/mol.113.089409. Epub 2013 Sep 27. PubMed PMID: 24077967.

Tzotzos S, Fischer B, Fischer H, Pietschmann H, Lucas R, Dupré G, Lemmens-Gruber R, Hazemi P, Prymaka V, Shabbir W. AP301, a synthetic peptide mimicking the lectin-like domain of TNF, enhances amiloride-sensitive Na+ current in primary dog, pig and rat alveolar type II cells. Pulm Pharmacol Ther. 2013 Jan 9. doi:pii: S1094-5539(13)00003-5.10.1016/j.pupt.2012.12.011. [Epub ahead of print] PubMed PMID: 23313096.

Hartmann EK, Boehme S, Duenges B, Bentley A, Klein KU, Kwiecien R, Shi C, Szczyrba M, David M, Markstaller K. An inhaled tumor necrosis factor-alpha-derived TIP peptide improves the pulmonary function in experimental  lung injury. Acta Anaesthesiol Scand. 2012 Dec 6. doi: 10.1111/aas.12034. [Epub ahead of print] PubMed PMID: 23216436.

Mascher D, Tscherwenka W, Mascher H, Fischer B. Sensitive determination of the peptide AP301--a motif of TNF-α--from human plasma using HPLC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Nov 1;908:18-22. doi: 10.1016/j.jchromb.2012.09.028. Epub 2012 Sep 21.

Lucas R, Yang G, Gorshkov BA, Zemskov EA, Sridhar S, Umapathy NS, Jezierska-Drutel A, Alieva IB, Leustik M, Hossain H, Fischer B, Catravas JD, Verin AD, Pittet JF, Caldwell RB, Mitchell TJ, Cederbaum SD, Fulton DJ, Matthay MA, Caldwell RW, Romero MJ, Chakraborty T. Protein kinase C-α and arginase I mediate pneumolysin-induced pulmonary endothelial hyperpermeability. Am J Respir  Cell Mol Biol. 2012 Oct;47(4):445-53. doi: 10.1165/rcmb.2011-0332OC. Epub 2012 May 10. PubMed PMID: 22582175; PubMed Central PMCID: PMC3488628.

Hazemi P, Tzotzos SJ, Fischer B, Andavan GS, Fischer H, Pietschmann H, Lucas R, Lemmens-Gruber R. Essential structural features of TNF-α lectin-like domain derived peptides for activation of amiloride-sensitive sodium current in A549 cells. J Med Chem. 2010 Nov 25;53(22):8021-9. doi: 10.1021/jm100767p. Epub 2010 Oct 27. PubMed PMID: 20979368; PubMed Central PMCID: PMC2996585.

Xiong C, Yang G, Kumar S, Aggarwal S, Leustik M, Snead C, Hamacher J, Fischer B, Umapathy NS, Hossain H, Wendel A, Catravas JD, Verin AD, Fulton D, Black SM,Chakraborty T, Lucas R. The lectin-like domain of TNF protects from listeriolysin-induced hyperpermeability in human pulmonary microvascular endothelial cells - a crucial role for protein kinase C-alpha inhibition. Vascul  Pharmacol. 2010 May-Jun;52(5-6):207-13. doi: 10.1016/j.vph.2009.12.010. Epub 2010 Jan 13. PubMed PMID: 20074664.