Maridebart cafraglutide — pharmacology
Molecular targets, mechanism of action, pharmacokinetics and interactions as characterised in humans.
§2Pharmacology
§2.1Molecular targets
Table 2. Molecular targets recorded for Maridebart cafraglutide, with the character of the interaction and the potency where the Institute holds it.
| Target | Interaction | Note |
|---|---|---|
| GIP receptor (GIPR) | Antagonist | Antibody arm |
| GLP-1 receptor (GLP1R) | Agonist | Conjugated peptide arms |
§2.2Mechanism of action
GLP-1 receptor agonism supplies appetite suppression; GIP receptor antagonism is proposed to act on adipose tissue and central pathways in a manner that also reduces adiposity. The antibody scaffold gives a very long half-life permitting monthly or less frequent administration, which is the principal practical differentiator.[1,2]
§2.3Pharmacokinetics
- Terminal half-life
- ≈21 days
- Time to maximum concentration
- several days
- Volume of distribution
- consistent with an IgG (small, largely vascular)
- Plasma protein binding
- not applicable in the small-molecule sense
- Clearance
- antibody-typical, FcRn-dependent
- Bioavailability
- antibody-typical subcutaneous bioavailability
Reticuloendothelial catabolism with FcRn recycling. The very long half-life means an adverse effect, once initiated, cannot be terminated by stopping treatment for several weeks — a consideration the Institute regards as material to benefit–risk.
§2.4Interactions
- Antibody-typical; no cytochrome interaction expected
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- Samms RJ, Coghlan MP, Sloop KW. How may GIP enhance the therapeutic efficacy of GLP-1?. Trends in Endocrinology & Metabolism 2020;31(6):410–421. doi:10.1016/j.tem.2020.02.006 · PMID 32396843
- Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB, Cui X, Briere DA, Cabrera O, Roell WC, Kuchibhotla U, Moyers JS, Benson CT, Gimeno RE, D’Alessio DA, Haupt A. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: from discovery to clinical proof of concept. Molecular Metabolism 2018;18:3–14. doi:10.1016/j.molmet.2018.09.009 · PMID 30473097
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.