MK-97

MK-97 (10 μM; 1 h RT, 30 min on ice) binds to the extracellular vestibule allosteric site of the purified human M₄ mAChR in a unique 'boomerang' conformation that establishes a distributed interaction network across transmembrane helices TM2, TM3, TM5, TM6, TM7, and ECL2, supporting its high-affinity positive allosteric modulation^[1].
MK-97 (0.1-100 μM; 18 h RT) acts as a positive allosteric modulator of ACh binding at WT human M₄ mAChRs expressed in Flp-In CHO cells with a pK_B of 6.3, with binding affinity critically dependent on W435^7.35 and Y89^2.61, and less dependent on F186^45.51 compared to first-generation PAMs^[1].
MK-97 (0.01-30 μM) enhances ACh-mediated Gαᵢ₁ activation at WT human M₄ mAChRs expressed in Flp-In CHO cells via positive allosteric modulation and exhibits allosteric agonism, with functional activity critically dependent on W435^7.35 but not Y89^2.61 or F186^45.51[1].
MK-97 (1:1 molar ratio with M₄ mAChR; 500 ns) maintains a stable, low-energy binding conformation in the extracellular vestibule allosteric site of the human M₄ mAChR, preserving key interactions with W435^7.35, Y89^2.61, and Y92^2.64 while maintaining the receptor's active state^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.