ERK2 Inhibitor

PD98059 is a potent and selective MEK inhibitor with an IC₅₀ of 5 µM. PD98059 binds to the inactive form of MEK, thereby preventing the activation of MEK1 (IC₅₀ of 2-7 µM) and MEK2 (IC₅₀ of 50 µM) by upstream kinases. PD98059 is a ERK1/2 signaling inhibitor. PD98059 is a ligand for the aryl hydrocarbon receptor (AHR), and suppresses TCDD binding (IC₅₀ of 4 μM) and AHR transformation (IC₅₀ of 1 μM). PD98059 also inhibits Mycobacterium bovis Bacillus CalmetteGuerin (BCG)-induced autophagy.

Erlotinib (CP-358774) is a selective, orally active EGFR tyrosine kinase inhibitor. Erlotinib also acts as a substrate and inhibitor of OATP2B1, with an IC₅₀ of approximately 0.079 μM for inhibiting OATP2B1-mediated uptake of estrone 3-sulfate. Erlotinib blocks EGFR phosphorylation, downstream signal transduction, as well as the growth and proliferation of cancer cells. Erlotinib inhibits MMP-10-mediated renal injury, fibrotic lesions, the ERK1/2, GSK-3β and β-catenin signaling pathways, fibronectin, α-SMA, collagen deposition, and renal injury markers. Erlotinib is metabolized via CYP3A to produce the active metabolite OSI-420. Erlotinib can be used in research related to non-small cell lung cancer, gastric cancer, papillary renal cell carcinoma, pancreatic cancer, renal fibrosis, and other conditions.

Leupeptin hemisulfate is a broad-spectrum protease inhibitor. Leupeptin hemisulfate inhibits serine, cysteine and threonine proteases, and regulates autophagy. Leupeptin hemisulfate reduces the expression levels of LC3B, iNOS, Cox-2, Beclin-1 and the level of endopeptidases; increases the levels of p62, Arg 1, Msr 1 and Mrc⁻1; and blocks the upregulation of p-PTEN, p-NF-κB, p-PI3K, p-Akt, p-p38 and ERK1/2. Leupeptin hemisulfate inhibits NO, ROS, proinflammatory cytokines, the IFN-γ/IL-10 ratio, phagolysosome fusion, mammalian lysosomal hydrolase activity and SARS-CoV-2 replication; and reverses impaired autophagic flux. Leupeptin hemisulfate is applicable to research related to chronic inflammatory diseases, edema, skin tumorigenesis, COVID-19 and respiratory infections.

SCH772984 is a highly selective and ATP-competitive ERK inhibitor, with IC₅₀s of 4 and 1 nM for ERK1 and ERK2, respectively. SCH772984 has antitumor activity in MAPK inhibitor-naive and MAPK inhibitor-resistant cells containing BRAF or RAS mutations.

Peptide R54 acetate (Pep R54 acetate) is a CXCR4 antagonist. Peptide R54 acetate inhibits CXCL12-dependent activation of pERK1/2 and pAKT. The combination of Peptide R54 acetate and Nivolumab (HY-P9903) suppresses melanoma growth. Peptide R54 (acetate) is applicable to research related to melanoma and ovarian cancer.

Astragaloside IV, an active component isolated from Astragalus membranaceus, suppresses the activation of ERK1/2 and JNK, and downregulates matrix metalloproteases (MMP)-2, (MMP)-9 in MDA-MB-231 breast cancer cells.

Ulixertinib (BVD-523; VRT752271) is a potent, orally active, highly selective, ATP-competitive and reversible covalent inhibitor of ERK1/2 kinases, with an IC₅₀ of <0.3 nM against ERK2. Ulixertinib (BVD-523; VRT752271) inhibits the phosphorylated ERK2 (pERK) and downstream kinase RSK (pRSK) in an A375 melanoma cell line.

Piperlongumine is a alkaloid, possesses ant-inflammatory, antibacterial, antiangiogenic, antioxidant, antitumor, and antidiabetic activities. Piperlongumine induces ROS, and induces apoptosis in cancer cell lines. Piperlongumine shows anti-cardiac fibrosis activity, suppresses myofibroblast transformation via suppression of the ERK1/2 signaling pathway. Piperlongumin could be used in the study of migrasome.

Temuterkib (LY3214996) is a highly selective inhibitor of ERK1 and ERK2, with IC₅₀ of 5 nM for both enzymes in biochemical assays. Temuterkib potently inhibits cellular p-RSK1 in BRAF and RAS mutant cancer cell lines. Temuterkib shows potent antitumor activities in cancer models with MAPK pathway alterations.

Gamma-linolenic acid (γ-Linolenic acid) is an orally active unsaturated fatty acid. Gamma-linolenic acid exerts anti-inflammatory effects by inhibiting the NF-κB pathway and the phosphorylation of ERK1/2 and JNK. At the same time, it exerts anticancer effects by inducing apoptosis (Apoptosis) in cancer cells. Additionally, Gamma-linolenic acid also has antioxidant and memory-improving effects. It holds promise for research in the fields of inflammation, neurology, and cancer diseases.

Ravoxertinib (GDC-0994) is an orally active ERK kinase inhibitor with an IC₅₀ of 6.1 nM and 3.1 nM for ERK1 and ERK2, respectively.

Apomorphine ((-)-Apomorphine) is a potent dopamine receptor agonist. Apomorphine also inhibit MAO-A and MAO-B. Apomorphine exerts neuroprotective effect and can relax rat corpus cavernosum. Apomorphine can inhibit ROS production, DNA fragmentation and inibit JNK and ERK1/2 phosphorylation. Apomorphine can enhance degradation of intracellular Aβ40 and Aβ42, reduces tau protein levels and inhibit MMP-9 expression. Apomorphine is a highly potent radical scavenger and iron chelator. Apomorphine can be used for the researches of dementia, parkinson's disease, alzheimer disease, breast carcinoma, and erectile dysfunction.

Erlotinib (CP-358774) Hydrochloride is a selective, orally active EGFR tyrosine kinase inhibitor. Erlotinib Hydrochloride also acts as a substrate and inhibitor of OATP2B1, with an IC₅₀ of approximately 0.079 μM for inhibiting OATP2B1-mediated uptake of estrone 3-sulfate. Erlotinib Hydrochloride blocks EGFR phosphorylation, downstream signal transduction, as well as the growth and proliferation of cancer cells. Erlotinib Hydrochloride inhibits MMP-10-mediated renal injury, fibrotic lesions, the ERK1/2, GSK-3β and β-catenin signaling pathways, as well as the deposition of fibronectin, α-SMA, collagen and renal injury markers. Erlotinib Hydrochloride is metabolized via CYP3A to produce the active metabolite OSI-420. Erlotinib Hydrochloride can be used in research related to non-small cell lung cancer, gastric cancer, papillary renal cell carcinoma, EGFR inhibitor resistance and renal fibrosis.

FR 180204 is an ATP-competitive and selective ERK inhibitor. FR 180204 inhibits ERK1 and ERK2 with IC₅₀s of 0.51 μM (K_i=0.31 μM) and 0.33 μM (K_i=0.14 μM), respectively.

ASN007 (ERK-IN-3) is a potent and orally active inhibitor of ERK. ASN007 inhibits ERK1/2 with low single-digit nM IC₅₀ values. ASN007 exhibits significant anti proliferative activity against various tumor cells. ASN007 can be used for the research of cancers driven by RAS mutations.

VX-11e is a potent, selective, and orally bioavailable inhibitor of ERK with K_i < 2 nM.

MK-8353 (SCH900353) is a potent, selective and orally available ERK1/2 inhibitor, with IC₅₀s of 23.0 nM and 8.8 nM, respectively; MK-8353 has antitumor activity.

ERK1/2 inhibitor 1 is a potent, orally bioavailable ERK1/2 inhibitor, showing 60% inhibition at 1 nM and an IC₅₀ of 3.0 nM against ERK1 and ERK2, respectively.

Senkyunolide I is an orally active, blood-brain barrier-permeable metabolite of Z-ligustilide (HY-N0401A). Senkyunolide I is isolated from Ligusticum chuanxiong. Senkyunolide I upregulates p-Erk1/2 and Nrf2/HO-1, and inhibits Caspase 3. Senkyunolide I alleviates Apoptosis. Senkyunolide I increases the pain threshold in mice and reduces acetic acid-induced writhing responses in mice. Senkyunolide I improves neurological deficits, reduces infarct volume and alleviates cerebral edema in rats with focal cerebral ischemia-reperfusion injury. Senkyunolide I protects renal function and structural integrity in a mouse model of renal ischemia-reperfusion injury. Senkyunolide I is applicable to research related to focal cerebral ischemia-reperfusion injury, migraine, and renal ischemia-reperfusion injury.

ASTX029 (Example 1) is a potent dual ERK1/2 inhibitor (IC₅₀: 2.7 nM). ASTX029 has anti-cancer activity.