ERKs (Extracellular-signal-regulated kinases) are widely expressed protein kinase intracellular signalling molecules that are involved in functions including the regulation of meiosis, mitosis, and postmitotic functions in differentiated cells. Many different stimuli, including growth factors, cytokines, virus infection, ligands for heterotrimeric G protein-coupled receptors, transforming agents, and carcinogens, activate the ERK pathway. In the MAPK/ERK pathway, Ras activates c-Raf, followed by mitogen-activated protein kinase kinase (abbreviated as MKK, MEK, or MAP2K) and then MAPK1/2 (below). Ras is typically activated by growth hormones through receptor tyrosine kinases and GRB2/SOS, but may also receive other signals. ERKs are known to activate many transcription factors, such as ELK1, and some downstream protein kinases. Disruption of the ERK pathway is common in cancers, especially Ras, c-Raf and receptors such as HER2.
||XMD17-109 is a novel, specific ERK-5 inhibitor, with an IC50 of 162 nM.
||SCH772984 potently inhibits ERK1 and ERK2 activity with IC50 values of 4 and 1 nM, respectively.
||VRT752271 is a reversible, ATP-competitive inhibitor of ERK1 and ERK2 kinases, with Km of <0.3 nM against ERK2.
||VX-11e is a potent, selective, and orally bioavailable inhibitor of ERK with Ki < 2 nM.
||XMD8-92 is a highly selective ERK5/BMK1 inhibitor with dissociation constant (Kd) value of 80 nM.
||DEL-22379 is an ERK dimerization Inhibitor. DEL-22379 readily binds to ERK2 with a Kd estimated in the low micromolar range, though binding is detectable even at low nanomolar concentrations. ERK2 dimerization is progressively inhibited with an IC50 of ~0.5 μM.
||GDC-0994 is an orally bioavailable inhibitor selective for ERK kinase activity with IC50 of 6.1 nM and 3.1 nM for ERK1 and ERK2, respectively.
||ERK5-IN-1 is a potent ERK5 inhibitor with an IC50 of 87±7 nM. ERK5-IN-1 also inhibits LRRK2[G2019S] with an IC50 of 26 nM.
||LY3214996 is a highly selective inhibitor of ERK1 and ERK2, with IC50 of 5 nM for both enzymes in biochemical assays.
||GDC-0994 hydrochloride is an orally bioavailable inhibitor selective for ERK kinase activity with IC50 of 6.1 nM and 3.1 nM for ERK1 and ERK2, respectively.
||Sanguinarine, a benzophenanthridine alkaloid derived from the root of Sanguinaria Canadensis, can stimulate apoptosis via activating the production of reactive oxygen species (ROS). Sanguinarine-induced apoptosis is associated with the activation of JNK and NF-κB.
||Tauroursodeoxycholate Sodium is an endoplasmic reticulum (ER) stress inhibitor. Tauroursodeoxycholate significantly reduces expression of apoptosis molecules, such as caspase-3 and caspase-12. Tauroursodeoxycholate also inhibits ERK.
||Mogrol is a biometabolite of mogrosides, and acts via inhibition of the ERK1/2 and STAT3 pathways, or reducing CREB activation and activating AMPK signaling.
||KO-947 is a small molecule inhibitor of extracellular-signal-regulated kinases 1 and 2 (ERK1/2), as a potential treatment for cancers in which the mitogen activated protein kinase (MAPK) pathway.
||AZD-0364 is a potent and selective ERK2 inhibitor extracted from patent WO2017080979A1, compound example 18, has an IC50 of 0.6 nM.
||BAY-885 (BAY885) is a highly potent and selective ERK5 inhibitor with IC50 of 35 nM and shows no binding to BRD4, in contrast to XMD8-92.