MK-8666 | CAS#1544739-76-5 | GPR40 Agonist

MedKoo Cat#: 571512 | Name: MK-8666

Description:

WARNING: This product is for research use only, not for human or veterinary use.

MK-8666 is a partial GPCR (G-protein-coupled receptor) agonist that is coordinated with the action of GPR40. GPR40, also known as free fatty acid (FFA) receptor 1 modulates fatty acid-induced insulin secretion in pancreatic beta cells and in intestinal enteroendocrine cells. Thus, MK-8666 has been investigated for treatment of type 2 diabetes mellitus and has been shown to robustly lower glucose without negative effects.

Chemical Structure

MK-8666

CAS#1544739-76-5 (free acid)

Theoretical Analysis

MedKoo Cat#: 571512

Name: MK-8666

CAS#: 1544739-76-5 (free acid)

Chemical Formula: C29H31NO6S

Exact Mass: 521.1872

Molecular Weight: 521.63

Elemental Analysis: C, 66.78; H, 5.99; N, 2.69; O, 18.40; S, 6.15

Price and Availability

This product is currently not in stock but may be available through custom synthesis. To ensure cost efficiency, the minimum order quantity is 1 gram. The estimated lead time is 2 to 4 months, with pricing dependent on the complexity of the synthesis (typically high for intricate chemistries). Quotes for quantities below 1 gram will not be provided. To request a quote, please click the button below. Note: If this product becomes available in stock in the future, pricing will be listed accordingly.

Bulk Inquiry

Related CAS #

2056254-98-7 (tris) 1544739-76-5 (free acid)

Synonym

MK-8666; MK 8666; MK8666

IUPAC/Chemical Name

(6R)-3-((2',6'-dimethyl-4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]-3-yl)methoxy)-5,5a,6,6a-tetrahydrocyclopropa[4,5]cyclopenta[1,2-c]pyridine-6-carboxylic acid

InChi Key

CODQKEMYZZKQAE-BHOIILBASA-N

InChi Code

InChI=1S/C29H31NO6S/c1-17-10-22(35-8-5-9-37(3,33)34)11-18(2)26(17)20-7-4-6-19(12-20)16-36-25-14-21-13-23-27(24(21)15-30-25)28(23)29(31)32/h4,6-7,10-12,14-15,23,27-28H,5,8-9,13,16H2,1-3H3,(H,31,32)/t23?,27?,28-/m1/s1

SMILES Code

O=C([O-])[C@@H]1C(C21)CC3=C2C=NC(OCC4=CC=CC(C5=C(C)C=C(OCCCS(=O)(C)=O)C=C5C)=C4)=C3.[NH3+]C(CO)(CO)CO

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

G-protein-coupled receptors (GPCRs) are signal receptors encoded by approximately 1000 Genes. They are targets in therapies involving neurotransmitters, hormones, peptides, chemokines, lipids, purines, ions, photons, and odorants, and thus can be used in treating central nervous system disorders, cancers, and cardiac, metabolic, and inflammatory diseases.

Instruction

View handling instruction

Preparing Stock Solutions

The following data is based on the product molecular weight 521.63 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

1: Krug AW, Vaddady P, Railkar RA, Musser BJ, Cote J, Ederveen A, Krefetz DG, DeNoia E, Free AL, Morrow L, Chakravarthy MV, Kauh E, Tatosian DA, Kothare PA. 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. Clin Transl Sci. 2017 Sep;10(5):404-411. doi: 10.1111/cts.12479. Epub 2017 Jul 20. PubMed PMID: 28727908; PubMed Central PMCID: PMC5593169. 2: Hyde AM, Liu Z, Kosjek B, Tan L, Klapars A, Ashley ER, Zhong YL, Alvizo O, Agard NJ, Liu G, Gu X, Yasuda N, Limanto J, Huffman MA, Tschaen DM. Synthesis of the GPR40 Partial Agonist MK-8666 through a Kinetically Controlled Dynamic Enzymatic Ketone Reduction. Org Lett. 2016 Nov 18;18(22):5888-5891. Epub 2016 Nov 1. PubMed PMID: 27802043. 3: Lu J, Byrne N, Wang J, Bricogne G, Brown FK, Chobanian HR, Colletti SL, DiSalvo J, Thomas-Fowlkes B, Guo Y, Hall DL, Hadix J, Hastings NB, Hermes JD, Ho T, Howard AD, Josien H, Kornienko M, Lumb KJ, Miller MW, Patel SB, Pio B, Plummer CW, Sherborne BS, Sheth P, Souza S, Tummala S, Vonrhein C, Webb M, Allen SJ, Johnston JM, Weinglass AB, Sharma S, Soisson SM. Structural basis for the cooperative allosteric activation of the free fatty acid receptor GPR40. Nat Struct Mol Biol. 2017 Jul;24(7):570-577. doi: 10.1038/nsmb.3417. Epub 2017 Jun 5. PubMed PMID: 28581512. 4: Lu S, Zhang J. Small Molecule Allosteric Modulators of G-Protein-Coupled Receptors: Drug-Target Interactions. J Med Chem. 2018 Feb 26. doi: 10.1021/acs.jmedchem.7b01844. [Epub ahead of print] PubMed PMID: 29457894