ERK Inhibitor

RP04340 is an orally active, selective pan-KRAS PROTAC degrader. RP04340 hijacks the CRBN E3 ligase and the cellular proteasome system to degrade KRAS, without degrading HRAS, NRAS, or common CRBN neosubstrates. RP04340 inhibits KRAS downstream signaling pathways, including pERK and DUSP6. RP04340 exhibits anticancer activity in various KRAS-mutant cancers. RP04340 can be used to study kras-driven cancers, including pancreatic ductal adenocarcinoma, colorectal cancer, and lung adenocarcinoma.

Norflurazon-¹³C,d₃ (SAN 9789-¹³C,d₃) is the d₃, ¹³C-labeled Norflurazon (HY-114849). Norflurazon (SAN 9789) is a pre-emergence Herbicide. Norflurazon non-competitively inhibits phytoene desaturase by competing with the enzyme cofactor and disrupts carotenoid biosynthesis, thereby leading to chlorophyll photodegradation and chlorosis. Norflurazon inhibits MGDG synthase, CDP-choline phosphotransferase, Omega-3 FAD7 desaturase, and PG delta-3-trans desaturase, and activates LysoPC-acyltransferase and Omega-3 FAD3 desaturase. Norflurazon inhibits photosynthetic membrane organization, mitochondrial respiration, ATP production, PI3K signaling, and ERK1/2 phosphorylation. Norflurazon activates MAPK P38 phosphorylation and ER stress signaling. Norflurazon induces morphological malformations and cardiovascular effects in zebrafish embryos.

Anti-inflammatory agent 100 (Compound (+)-4S-23) is an anti-inflammatory agent. Anti-inflammatory agent 100 inhibits MAPK and NF-κB signaling, and also inhibits NF-κB pathway by suppressing the phosphorylation of IκB-α and blocking nuclear translocation of phosphorylated p65. Anti-inflammatory agent 100 inhibits NO production (IC₅₀: 0.5 μM) and TNF-α, IL-6, IL-1β secretion.

KRASG12D-IN-7 is a selective KRAS^G12D inhibitor. KRASG12D-IN-7 displays strong binding activity for KRAS^G12D in both its GDP- and GTP- bound states, with K_d value of 1.12 nM and 1.86 nM, respectively. KRASG12D-IN-7 inhibits the proliferation of KRAS^G12D harboring AsPC-1 cells with an IC₅₀ value of 10 nM and suppresses MAPK signaling. KRASG12D-IN-7 induces G0/G1 phase arrest and apoptosis in AsPC-1 cells, and strongly inhibits their colony formation. KRASG12D-IN-7 can be used for the study of cancers harboring KRAS^G12D mutation, particularly pancreatic ductal adenocarcinoma (PDAC).

FLT3-IN-40 is a type I ATP-competitive FLT3 inhibitor with an IC₅₀ of 16.26 nM. FLT3-IN-40 reduces the autophosphorylation level of FLT3 and the phosphorylation level of downstream ERK. FLT3-IN-40 exhibits antiproliferative, cell cycle regulatory and apoptosis-inducing activities. FLT3-IN-40 can be used in research related to acute myeloid leukemia.

ATX inhibitor 26 is an Autotaxin (ATX) inhibitor with an IC₅₀ of 57 nM in human plasma. ATX inhibitor 26 inhibits cell migration and collagen gel contraction. ATX inhibitor 26 has significant anti-fibrotic effects, reducing collagen deposition in a Bleomycin (BLM) (HY-108345)-induced pulmonary fibrosis model.

EGFR-IN-182 (Compound 4) is an EGFR inhibitor with an IC₅₀ value of 199 nM. EGFR-IN-182 inhibits HSP90 and PI3K, with IC₅₀ values of 5.007 and 13.596 μM respectively. EGFR-IN-182 exhibits strong anti-proliferative activity against MCF-7 and MDA-MB-231 cells. EGFR-IN-182 downregulates Cyclin D1, inducing cell cycle arrest; it enhances the activity of caspase-9, inducing cell apoptosis. EGFR-IN-182 downregulates the expressions of ERK and AKT. EGFR-IN-182 can be used for research on breast cancer.

Enniatin B-¹³C₃₃ is the ¹³C-labeled Enniatin B (HY-N3806). Enniatin B is a Fusarium mycotoxin that acts as an ionophore to form cation-selective membrane channels, disrupt ion homeostasis and mitochondrial function, inhibit cell proliferation, and induce apoptosis, while modulating ERK, p38 MAPK, and STAT3 signaling pathways. Enniatin B is used in research on atherosclerosis, hypercholesterolemia, cervical cancer, and colon adenocarcinoma.

PROTAC ALK degrader-4 is a ALK PROTAC degrader with a DC₅₀ of 445.25 nM. PROTAC ALK degrader-4 induces concentration- and time-dependent degradation of EML4-ALK, as well as concentration-dependent degradation of ALK^F1174L. PROTAC ALK degrader-4 downregulates 390 proteins in NCI-H3122 cells, including the targets of ceritinib (ALK, IGF-1R) and downstream molecules ERK1/2 and STAT3. PROTAC ALK degrader-4 exerts antiproliferative activity in ALK-positive cancer cells. ALK degrader-4 can be used in studies related to lung adenocarcinoma.

SOS1-IN-18 (Compound 8) is the inhibitor for Son of Sevenless 1 protein (SOS1) with a K_D of 2.6 nM, and inhibits SOS1-KRAS G12C interaction with an IC₅₀ of 3.4 nM. SOS1-IN-18 inhibits the phosphorylation of ERK in H358 with an IC₅₀ of 31 nM, inhibits the proliferation of H358 with an IC₅₀ of 5 nM.

Limocitrin is a flavonol glycoside. Limocitrin inhibits AKT phosphorylation and JNK phosphorylation, upregulates p38 phosphorylation, and inhibits ERK1/2 phosphorylation, thereby blocking MAPK signaling. Limocitrin induces Apoptosis through the mitochondrial pathway, death receptor-mediated signaling, Caspase activation, and G2/M cell cycle arrest. Limocitrin possesses anti-inflammatory and anticancer properties. Limocitrin can be used for research on oral squamous cell carcinoma and chronic myeloid leukemia.

ERK2 allosteric-IN-1 (compound 1) is a selective and allosteric ERK2 inhibitor with the IC₅₀ of 11 μM.

Oxypeucedanin (Standard) is a furanocoumarin derivative found in Angelica dahurica. Oxypeucedanin (Standard) is an orally active PI3K/AKT/NF-κB, MAPK, and ROS inhibitor. Oxypeucedanin (Standard) induces cell cycle arrest and apoptosis. Oxypeucedanin (Standard) inhibits hKv1.5 channel currents (IC₅₀: 76 nM). Oxypeucedanin (Standard) exhibits anticancer, anti-inflammatory, antioxidant and antiarrhythmic activities.

Hordenine sulfate (Ordenina sulfate; Peyocactine sulfate) is a multifunctional alkaloid with oral activity and blood-brain barrier penetration. Hordenine sulfate inhibits LPS-induced phosphorylation of p38, JNK, ERK1/2, p65, IκB, and AKT, prevents p65 nuclear translocation, and suppresses inflammatory cytokines and mediators. Hordenine sulfate promotes M2 macrophage polarization, restores blood-milk barrier integrity, alleviates oxidative stress by reducing ROS and MDA, and attenuates LPS-induced lung injury and pulmonary edema. Hordenine sulfate inhibits cAMP production, CREB phosphorylation, and MITF expression, thereby suppressing melanin synthesis in melanocytes and reconstructed epidermis. Hordenine sulfate activates the Wnt/β-catenin signaling pathway, promotes dermal papilla cell proliferation and hair shaft elongation, and accelerates hair regeneration. Hordenine sulfate activates DRD2, acts as a D3R partial agonist, α2A-AR full agonist, and 5-HT2A-R antagonist, and inhibits SERT and DAT. Hordenine sulfate inhibits α-synuclein accumulation and ameliorates motor deficits in Parkinson's disease models. Hordenine sulfate limits alcohol intake, reduces relapse drinking behavior, and modulates alcohol-induced conditioned place preference. Hordenine sulfate can be used for research on mastitis, skin pigmentation, acute lung injury, foodborne diseases, hair loss, Parkinson's disease, bacterial infections, and alcohol use disorder.

Anticancer agent 301 is an anticancer agent. Anticancer agent 301 selectively downregulates the phosphorylation level of ERK1/2 without affecting the NF-κB p65 subunit. Anticancer agent 301 exhibits antiproliferative activity against breast cancer cells and can be used in breast cancer-related research.

WH23 is a dehydrogenase/reductase SDR family member 11 (DHRS11) inhibitor with IC₅₀ values of 0.037 μM. WH23 binds to DHRS11, forming a hydrogen bond with the enzyme’s His210 residue. WH23 suppresses androgen receptor mRNA and protein expression, reduces c-Myc expression, and inhibits cancer cell proliferation. WH23 inhibits PI3K/AKT signaling by reducing phosphorylation of PDK1, AKT, mTOR, and ERK. WH23 enhances Capivasertib (HY-15431)-induced cytotoxicity and apoptosis. WH23 can be used for the research of luminal androgen receptor-positive triple-negative breast cancer.

K20 is a potent and selective KRas G12C inhibitor with an IC₅₀ of 1.16 µM. K20 shows anticancer activity in H358 cells (IC₅₀= 0.78 µM). K20 decreases the levels of phosphorylated Erk and leads to cancer cell apoptosis. K20 suppresses NCI-H358 tumor growth with a TGI of 41% without causing obvious toxicity.

OP-1118 (Fidaxomicin metabolite OP-1118) is an orally active dual inhibitor of NF-κB and ERK1/2, with low systemic plasma exposure, no accumulation, and primary excretion via feces. By inhibiting the phosphorylation of NF-κB and ERK1/2 and reducing the expression of pro-inflammatory cytokines, OP-1118 exerts significant anti-inflammatory, cytoprotective, anti-apoptotic and antibacterial activities. In Clostridium difficile infection models, OP-1118 effectively blocks toxin-mediated intestinal inflammation, cell rounding, histological damage and apoptosis, and its protective effect can be reversed by PMA (HY-18739).

LC-SF-14 is a selective dual inhibitor of SHP2 and FGFR (IC₅₀ values are 71.6 and 8.9 nM, respectively). LC-SF-14 inhibits FGFR2-FRS2α-SHP2-MAPK signaling and ERK phosphorylation. LC-SF-14 inhibits the proliferation of KATOIII cancer cells (IC₅₀: 9.2 nM). LC-SF-14 has antitumor activity in the SNU-16 xenograft mouse model. LC-SF-14 can be used in FGFR2-driven gastric cancer research.

PDGFRA/CAIX/XII-IN-1 is an inhibitor of PDGFRA, CA IX and CA XII, with an IC₅₀ of 20 nM against PDGFRA, a K_i of 93.3 nM against CA IX, and a K_i of 80.0 nM against CA XII. PDGFRA/CAIX/XII-IN-1 binds to the ATP-binding pocket of PDGFRA and blocks the downstream STAT3, AKT and ERK1/2 signaling pathways. PDGFRA/CAIX/XII-IN-1 induces G0/G1 cell cycle arrest and endogenous apoptosis (Apoptosis), including cleavage of PARP-1, caspase-9 and caspase-3, activation of caspase 3/7, and down-regulation of Mcl-1. PDGFRA/CAIX/XII-IN-1 exhibits antiproliferative activity in eosinophilic leukemia cells. PDGFRA/CAIX/XII-IN-1 can be used for the research of leukemia.