DMB

DMB (CAS 281209‑71‑0) is an orally active GLP‑1R agonist. It activates GLP‑1R by forming hydrogen bonds with sites such as Tyr42, Cys71, and Ser84 and enhancing hydrophobic interactions, elevates cAMP, and promotes glucose-dependent insulin secretion from pancreatic β cells; in neurons, it exerts anti-apoptotic and neuroprotective effects via the cAMP/PKA/CREB pathway. Some studies also suggest it can directly activate GSDMD to induce pyroptosis and inhibit tumor growth.

Cell level: In cells expressing human GLP‑1R, DMB shows a Ki of ~13.25 μM for the receptor, and an EC50 of ~0.1 μM (101 nM) for inhibiting forskolin-induced cAMP production. Effective concentrations are mostly in the 10⁻⁷–10⁻⁵ M range, used to evaluate cAMP elevation, enhanced insulin secretion, and survival protection in ischemia/apoptosis model neurons. Specific incubation times and dosing regimens depend on each study design (mostly several hours to 24 h treatment).

Animal level: In mice, oral DMB at ~5 μmol/kg can reduce fasting blood glucose and enhance the insulin response after glucose challenge; in rat/mouse middle cerebral artery occlusion models, intragastric administration (doses at the μmol/kg level, typically for several consecutive days before and/or after modeling) can reduce infarct volume and lower neurological deficit scores, showing GLP‑1R-dependent neuroprotection.

The above doses are for reference in protocol design only; specific conditions should be optimized according to the target literature.

References:

[1] Zhang H, Liu Y, Guan S, Qu D, Wang L, Wang X, Li X, Zhou S, Zhou Y, Wang N, Meng J, Ma X. An Orally Active Allosteric GLP-1 Receptor Agonist Is Neuroprotective in Cellular and Rodent Models of Stroke. PLoS One. 2016 Feb 10;11(2):e0148827. doi: 10.1371/journal.pone.0148827. PMID: 26863436; PMCID: PMC4749391.

[2] Girdhar K, Dehury B, Kumar Singh M, Daniel VP, Choubey A, Dogra S, Kumar S, Mondal P. Novel insights into the dynamics behavior of glucagon-like peptide-1 receptor with its small molecule agonists. J Biomol Struct Dyn. 2019 Sep;37(15):3976-3986. doi: 10.1080/07391102.2018.1532818. Epub 2018 Nov 17. PMID: 30296922.