mrk

MRK-016 is a selective GABAA α5 receptor inverse agonist/ negative allosteric modulator, (IC50=3 nM) with the advantages of being orally available and penetrating the blood-brain barrier.MRK-016 increases long time period potentiation (LTP) in mouse hippocampal slices, with memory-improvement, antidepressant, and pain-treating effects.

MRK003 is a γ-secretase inhibitor exhibits promising in vitro pre-clinical activity in multiple myeloma and non-Hodgkin's lymphoma. MRK003 treatment induced caspase-dependent apoptosis and inhibited proliferation of MM and NHL cell lines and patient cells. Examination of signaling events after treatment showed time-dependent decrease in levels of the notch intracellular domain, Hes1 and c-Myc. MRK003 downregulated cyclin D1, Bcl-Xl and Xiap levels in NHL cells and p21, Bcl-2 and Bcl-Xl in MM cells. In addition, MRK003 caused an upregulation of pAkt, indicating crosstalk with the PI3K/Akt pathway.

M443 is a potent small molecule inhibitor of MRK that inhibits radiation-induced activation of p38 and Chk2 and can be used in cancer research.

MK-0343, also known as MRK-409, is a GABAA receptor subtype-selective partial agonist that exhibits non-sedating anxiolytic activity in preclinical species but induces sedation in humans, binding with high affinity to α1-, α2-, α3-, and α5-containing human recombinant GABA(A) receptors while demonstrating greater agonist efficacy at α3 relative to α1 subtypes, thereby providing mechanistic insight into subtype-specific modulation of inhibitory neurotransmission.

CMPD167 (MRK-1) is a potent, orally active inhibitor of CCR5 with significant in vitro antiviral efficacy [1].

MRK-560 is an effective and brain-penetrant inhibitor of γ-secretase.

MRK-952 is a NUDIX hydrolase inhibitor. NUDIX enzymes play a role in cellular metabolism, homeostasis, and mRNA processing.

MRK-990 is an inhibitor of PRMT that targets both PRMT5 and PRMT9, with IC50 values of 30 nM and 10 nM, respectively.

MRK-740-NC is an inhibitor of the PRDM7/9 histone methyltransferase. Acting as the negative control compound for MRK-740, MRK-740-NC lacks inhibitory activity on PRDM7 and PRDM9 because the methylpyridine portion of MRK-740 is replaced with a phenyl group.

MRK-623 (Compound 14k) is a potent, orally active agonist of the GABA A receptor with high affinity for subunits α1, α2, α3, and α5, exhibiting Ki values of 0.85 nM, 3.7 nM, 4.0 nM, and 0.53 nM, respectively. Notably, MRK-623 demonstrates anxiolytic effects [1].

MRK-740 is a potent and selective inhibitor of PRDM9 histone methyltransferase.MRK-740 inhibits other histone methyltransferases and inhibits PRDM9-dependent H3K4 trimethylation.

MRK-898, an orally active modulator of the GABA(A) receptor, selectively interacts with the α1, α2, α3, and α5 subunits, displaying K i values of 1.2 nM, 1.0 nM, 0.73 nM, and 0.50 nM, respectively. It is noteworthy that the α1-containing receptors of GABA(A) are classified as "sedative," whereas receptors containing α2 and/or α3 are designated as "anxiolytic" subtype(s) [1].