R&D Initiatives

We have several ongoing R&D projects at Red Glead Discovery (RGD).

Project Nile aims at developing novel compounds for an epigenetic target in the treatment of cancer. This project is a collaboration between RGD, SARomics Biostructures (SBX) and a research group led by Professor Jonas Nilsson at Sahlgrenska Hospital (Gothenburg, Sweden). Candidate drug development activities are supported by a research grant from Vinnova (the Swedish innovation agency).

Project Ganges, a collaboration between SARomcs Biostructures and RGD, is built on the foundation of a successful fragment screen, where hits for this bromodomain-class target were identified using our exclusive WAC technology. Further validation led to X-ray co-crystal structures revealing a possibility for developing a PPI inhibitor-type molecule. The project is currently in the hit expansion phase and entering hit-to-lead.

A previous project has been spun out into a separate company, Apoglyx, where RGD is a co-owner. Apoglyx research is based on aquaporins, a group of structures in cell membranes discovered in 1991 by Peter Agre and awarded with the Nobel Prize in Chemistry 2003. Aquaporins have been recognized as potential drug targets and may have roles for development of autoimmune diseases, cancer, diabetes, malaria, inflammation and sepsis. The lead compound – RG100204, has shown promising effects against sepsis when evaluated in vivo.

Pipeline

Hit Identification Lead Identification Lead Optimisation Candidate Drug Clinical Phase Partner

SACRA

Ganges

– Bromodomain protein – Several

Nile

– Bromodomain protein – Oncology

APOGLYX

– Aquaporin – Sepsis

We currently have several ongoing internal drug discovery projects in our pipeline.

Science

Red Glead Discovery (RGD) invests heavily in remaining at the forefront of research and innovation. Ninety-five percent of our staff currently work in lab- or other science-based positions. In addition to actively producing peer-reviewed research papers, we have contributed to several patents for both clients and internal RGD projects. A number of our scientists are appointed lecturers at Lund University and Lund Technical University and serve in advisory roles shaping the teaching curriculum in chemistry / biomedicine and chemical engineering programs respectively. RGD actively engages in collaboration with academia to address societal challenges, welcoming diploma workers to participate in projects from all of our scientific disciplines.

An area of focus for RGD is on green chemistry. Organic solvents are used to facilitate chemical reactions, but they do not add any value to the final product and in most cases, they originate from petroleum and end up as waste. We have initiated a collaboration with researchers at the Centre for Analysis and Synthesis at Lund University. The project aims to develop methods for organic synthesis in water.  Our approach is to recycle water and the catalyst used, so the created waste is close to zero. The long-term goal is to be able to synthesize pharmaceuticals with low environmental impact.

Diploma Work

Federico Balgera 2022, Lund University

Evaluation of gold-based compounds as Plasmodium falciparum aquaglyceroporin inhibitors

Andrea Ölander 2022, Lund University

Greening peptide chemistry by using NBP as solvent for SPPS

Albin Olsson 2021, Lund University

Rare Earth Triflate/Alanine Catalyzed Diels Alder and Michael Reactions in Water and an Alternative Pyrrole Synthesis

Kajsa Andréasson Dahlgren 2021, Lund University

Validation of a 3D culture model for toxicity studies in malignant and non-cancerous cells

Artur Sahakjan 2020, Lund University

Fragment screening using WAC towards new SMARCA4 inhibitors

Sofi Gummeson 2020, Lund University

Synthesis of a 13C-labeled tool compound for diagnostic applications

Tomas Laszlo Szakacs 2019, Lund University

Peptide fragment screening towards a new inhibitor of neutrophil elastase

Publications

RG100204, A Novel Aquaporin-9 Inhibitor, Reduces Septic Cardiomyopathy and Multiple Organ Failure in Murine Sepsis

Mohammad S, O'Riordan CE, Verra C, Aimaretti E, Alves GF, Dreisch K, Evenäs J, Gena P, Tesse A, Rützler M, Collino M, Calamita G, Thiemermann C.
Front Immunol. 2022 Jun 14;13:900906.

Sialic Acid Derivatives Inhibit SiaT Transporters and Delay Bacterial Growth

Bozzola T, Scalise M, Larsson CU, Newton-Vesty MC, Rovegno C, Mitra A, Cramer J, Wahlgren WY, Radhakrishnan Santhakumari P, Johnsson RE, Schwardt O, Ernst B, Friemann R, Dobson RCJ, Indiveri C, Schelin J, Nilsson UJ, Ellervik U.
ACS Chem Biol. 2022 Jul 15;17(7):1890-1900.

Characterization of the Aquaporin-9 Inhibitor RG100204 In Vitro and in db/db Mice

Massaro A, Timpka S, Reimer MK, Kjellbom P, Beitz E, Johanson U, Rützler M, Calamita G.
Cells, 11(19), 3118.

Discovery and Optimization of the First Highly Effective and Orally Available Galectin-3 Inhibitors for Treatment of Fibrotic Disease.

Zetterberg FR, MacKinnon A, Brimert T, Gravelle L, Johnsson RE, Kahl-Knutson B, Leffler H, Nilsson UJ, Pedersen A, Peterson K, Roper JA, Schambye H, Slack RJ, Tantawi S.
J Med Chem. 2022 Oct 13;65(19):12626-12638.

Molecular Dynamics Studies of Therapeutic Liquid Mixtures and Their Binding to Mycobacteria

Monteiro H, Santos F, Paiva A, Duarte ARC, Ferreira RJ.
Front Pharmacol. 2021 Apr 20;12:626735.

Evolution of Nitrogen-Based Alkylating Anticancer Agents

Lehmann F, Wennerberg J.
Processes 2021, 9, 377

An Aldehyde Responsive, Cleavable Linker for Glucose Responsive Insulins

Mannerstedt K, Mishra NK, Engholm E, Lundh M, Madsen CS, Pedersen PJ, Le-Huu P, Pedersen SL, Buch-Månson N, Borgström B, Brimert T, Fink LN, Fosgerau K, Vrang N, Jensen KJ.
Chemistry. 2021 Feb 10;27(9):3166-3176.

Melflufen: A Journey from Discovery to Multi-Kilogram Production

Lehmann F, Wennerberg J.
Complete Accounts of Integrated Drug Discovery and Development: Recent Examples from the Pharmaceutical Industry Volume 3, Chapter 5 pp 157-177, 2020

NMR Study of the Secondary Structure and Biopharmaceutical Formulation of an Active Branched Antimicrobial Peptide

Castiglia F, Zevolini F, Riolo G, Brunetti J, De Lazzari A, Moretto A, Manetto G, Fragai M, Algotsson J, Evenäs J, Bracci L, Pini A, Falciani C.
Molecules. 2019 Nov 25;24(23):4290.

Monosaccharide Derivatives with Low Nanomolecular Lectin Affinity and High Selectivity Based on Combined Fluorine-Amide, Phenyl-Arginine, Sulfur-π, and Halogen Bond Interactions

Zetterberg FR, Peterson K, Johnsson RE, Brimert T, Håkansson M, Logan DT, Leffler H, Nilsson UJ.
ChemMedChem. 2018 Jan 22;13(2):133-137.

Structural Insights into the Calcium-Mediated Allosteric Transition in the C-Terminal Domain of Calmodulin from Nuclear Magnetic Resonance Measurement

Kukic P, Lundström P, Camilloni C, Evenäs J, Akke M, Vendruscolo M.
Biochemistry. 2016 Jan 12;55(1):19-28.

Identification of indole inhibitors of human hematopoietic prostaglandin D2 synthase (hH-PGDS)

Edfeldt F, Evenäs J, Lepistö M, Ward A, Petersen J, Wissler L, Rohman M, Sivars U, Svensson K, Perry M, Feierberg I, Zhou XH, Hansson T, Narjes F.
Bioorg Med Chem Lett. 2015 Jun 15;25(12):2496-500.

HTS followed by NMR based counterscreening. Discovery and optimization of pyrimidones as reversible and competitive inhibitors of xanthine oxidase

Evenäs J, Edfeldt F, Lepistö M, Svitacheva N, Synnergren A, Lundquist B, Gränse M, Rönnholm A, Varga M, Wright J, Wei M, Yue S, Wang J, Li C, Li X, Chen G, Liao Y, Lv G, Tjörnebo A, Narjes F.
Bioorg Med Chem Lett. 2014 Mar 1;24(5):1315-21.