GtoPdb pre-release ligands (2021.1)

These are some of the ligands under curation (pre-release) in the Guide to Pharmacology. We expect them to be available on the website at the next database release (2021.1).

Ligand ID: 11395
Names: MK-7110
Comment: MK-7110 (originally OncoImmune’s CD24Fc) is a synthetic protein that fuses the nonpolymorphic regions of CD24 (which is an agonist of Siglec-10) to the Fc region of human IgG1 [PubMed ID:19264983]. being investigated as a modulator of the innate immune system, originally as an intervention to ameliorate graft-versus-host disease in leukemia patients receiving stem cell transplants, or autoimmune diseases. The peptide’s sequence was extracted from OncoImmune’s patent US20130231464A1 the first 30 amino acids are the CD24 region and the remainder belong to the IgG1 Fc domain.
Coronavirus relevance: A clinical stage synthetic fusion protein and CD24 mimetic, that enhances CD24/SIGLEC10 suppression of DAMP-triggered activation of the immune response and associated tissue damage. Repositioned to combat COVID-19 inflammation (currently Phase 3).

Ligand ID: 11421
Names: emvododstat
Comment: Emvododstat (PTC299) is an orally bioavailable inhibitor of dihydroorotate dehydrogenase (DHODH) that was developed by PTC Therapeutics for anti-cancer potential. It inhibits de novo pyrimidine nucleotide (UMP) biosynthesis and exhibits broad activity against leukemia in vitro and in vivo.
Coronavirus relevance: Emvododstat inhibits replication of SARS-CoV-2 in vitro (EC50 2.0-31.6 nM) and other RNA viruses. It blocks production of inflammatory cytokines in infected cell cultures.

2D structure of emvododstat







Ligand ID: 11470
Names: ensovibep (MP0420)
Comment: MP0420 is a DARPin that binds to the SARS-CoV-2 spike glycoprotein, and offers virus neutralising potential. It is being progressed to clinical trial by Molecular Partners and Novartis. DARPins are protein-based therapeutics, with the high selectivity and affinity of antibodies, but are around 10% of the size. They are easier to manufacture than whole antibodies, and may be suitable for subcutaneous administration rather than infusion. Molecular Partners have developed two multi-valent DARPins that are designed to engage multiple sites of the SARS-CoV-2 spike glycoprotein. Novartis and Molecular Partners are working together on both MP0420 and MP0423 for COVID-19.

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