SerBut

SerBut
Clinical data
Other namesO-Butyryl-L-serine; O-Butanoyl-L-serine; Serine–butyrate conjugate; Seryl-butyrate
Drug classButyric acid prodrug
ATC code
  • None
Identifiers
  • (2S)-2-amino-3-butanoyloxypropanoic acid
CAS Number
PubChem CID
ChemSpider
Chemical and physical data
FormulaC7H13NO4
Molar mass175.184 g·mol−1
3D model (JSmol)
  • CCCC(=O)OC[C@@H](C(=O)O)N
  • InChI=1S/C7H13NO4/c1-2-3-6(9)12-4-5(8)7(10)11/h5H,2-4,8H2,1H3,(H,10,11)/t5-/m0/s1
  • Key:HTDGDRZVMBNEMO-YFKPBYRVSA-N

SerBut, also known as O-butyryl-L-serine or as seryl-butyrate, is an ester conjugate of the short-chain fatty acid butyric acid (butyrate) and the amino acid serine. It is a prodrug of butyric acid with high oral bioavailability and enhanced blood–brain barrier permeability in animals. The drug makes use of amino acid transporters for absorption and transport. It shows anti-inflammatory effects in rodents including in models of autoimmune diseases and neuroinflammation. The use of butyric acid itself is hindered by its rapid metabolism in the gastrointestinal tract and other limitations. The chemical synthesis of SerBut has been described. SerBut was first described in the scientific literature by 2024.

See also

References

  1. 1 2 3 4 Coccia C, Bonomi F, Lo Cricchio A, Russo E, Peretti S, Bandini G, et al. (August 2024). "The Potential Role of Butyrate in the Pathogenesis and Treatment of Autoimmune Rheumatic Diseases". Biomedicines. 12 (8): 1760. doi:10.3390/biomedicines12081760. PMC 11351188. PMID 39200224. Recent research has also focused on improving the bioavailability of butyrate. The development of butyrate as a drug is particularly difficult due to its poor oral bioavailability, as it is rapidly metabolized in the gut and has low potency (hence, necessitating high dosing). A recent study analyzed a new form of butyrate, esterified into serine (creating SerBut), showing how this enhanced its systemic uptake by aiding its escape from the gut [60]. In mouse models of collagen-induced arthritis, SerBut substantially ameliorated disease severity, modulated key immune cell populations, and reduced inflammatory responses [61].
  2. 1 2 3 4 Ning S, Zhang Z, Zhou C, Wang B, Liu Z, Feng B (2024). "Cross-talk between macrophages and gut microbiota in inflammatory bowel disease: a dynamic interplay influencing pathogenesis and therapy". Frontiers in Medicine. 11 1457218. Lausanne. doi:10.3389/fmed.2024.1457218. PMC 11443506. PMID 39355844. Recently, Cao et al. developed a prodrug called SerBut by combining butyric acid with serine. Oral administration of SerBut significantly elevates butyric acid levels in mice while also increasing regulatory T cells and reducing the proportion of M1-like macrophages to modulate immune responses. As a promising therapeutic agent for autoimmune and inflammatory diseases, SerBut may potentially play a role in future IBD treatment (42).
  3. 1 2 He Q, Zhang L (November 2025). "Targeted drug delivery systems for rheumatoid arthritis: advancing precision medicine in autoimmune therapies". Journal of Materials Chemistry B. 13 (46): 14949–14966. doi:10.1039/d5tb01296a. PMID 41163624. Oral drug delivery must surmount the gastrointestinal tract's tripartite barrier: acidic/enzymatic degradation in the stomach, the mucus layer and tight junctions limiting intestinal absorption, and microbial interactions in the gut lumen. Prodrug engineering strategies, such as serine–butyrate conjugates (SerBut), leverage amino acid transporters to enhance systemic absorption while masking drug reactivity in RA and multiple sclerosis models.88
  4. 1 2 3 4 5 6 7 Cao S, Budina E, Raczy MM, Solanki A, Nguyen M, Beckman TN, et al. (May 2024). "A serine-conjugated butyrate prodrug with high oral bioavailability suppresses autoimmune arthritis and neuroinflammation in mice". Nature Biomedical Engineering. 8 (5): 611–627. doi:10.1038/s41551-024-01190-x. PMC 11161413. PMID 38561491.
  5. 1 2 3 4 Beckman TN, Volpatti LR, Norton de Matos S, Slezak AJ, Reda JW, Weinstock A, et al. (August 2025). "A prometabolite strategy inhibits cardiometabolic disease in an ApoE-/- murine model of atherosclerosis". JCI Insight. 10 (15) e191090. doi:10.1172/jci.insight.191090. PMC 12333940. PMID 40779455.