1544739-75-4
Chemical Structure
MK-8666
- CAS No.: 1544739-75-4
- Formula:C29H31NO6S
- Molecular Weight:521.62
InChIKey: CODQKEMYZZKQAE-QPVYNBJUSA-N
SMILES: O=C(O)[C@H]1[C@]([H])(CC2=C3C=NC(OCC4=CC(C5=C(C=C(C=C5C)OCCCS(=O)(C)=O)C)=CC=C4)=C2)[C@@]13[H]
Biological Activity: MK-8666 is an orally active selective FFA1 agonist of GPR40 that stimulates glucose-dependent insulin secretion. MK-8666 binds to the allosteric partial agonist site, activates Gq signaling, positively modulates GPR40 in synergy with endogenous free fatty acids, and exhibits functional and ligand-binding cooperativity with AgoPAM as well as induced-fit conformational changes. MK-8666 can be used for research on type 2 diabetes[1][2][3][4][5][6].
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MK-8666 | MK-8666 is an orally active selective FFA1 agonist of GPR40 that stimulates glucose-dependent insulin secretion. MK-8666 binds to the allosteric partial agonist site, activates Gq signaling, positively modulates GPR40 in synergy with endogenous free fatty acids, and exhibits functional and ligand-binding cooperativity with AgoPAM as well as induced-fit conformational changes. MK-8666 can be used for research on type 2 diabetes. | |||||||||||||||||||||
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References
- [1]. Shang J, et al. Bioactivation of GPR40 Agonist MK-8666: Formation of Protein Adducts in Vitro from Reactive Acyl Glucuronide and Acyl CoA Thioester. Chemical research in toxicology. 2020 Jan 21;33(1):191-201. [Content Brief]
- [2]. Lu S, et al. Small Molecule Allosteric Modulators of G‑Protein-Coupled Receptors: Drug–Target Interactions. Journal of medicinal chemistry. 2019 Jan 10;62(1):24-45. [Content Brief]
- [3]. Ruck RT, et al. The catalysis laboratory at Merck: 20 years of catalyzing innovation. ACS Catalysis. 2023 Jan 6;13(1):475-503.
- [4]. Hyde AM, et al. Synthesis of the GPR40 Partial Agonist MK-8666 through a Kinetically Controlled Dynamic Enzymatic Ketone Reduction. Organic letters. 2016 Nov 18;18(22):5888-5891. [Content Brief]
- [5]. Krug AW, et al. Leveraging a Clinical Phase Ib Proof-of-Concept Study for the GPR40 Agonist MK-8666 in Patients With Type 2 Diabetes for Model-Informed Phase II Dose Selection. Clinical and translational science. 2017 Sep;10(5):404-411. [Content Brief]
- [6]. Lu J, et al. Structural basis for the cooperative allosteric activation of the free fatty acid receptor GPR40. Nature structural & molecular biology. 2017 Jul;24(7):570-577. [Content Brief]
