p38 MAPK Inhibitor

Tubeimoside I is an orally active HSPD1 inhibitor. Tubeimoside I inhibits NF-κB, MAPK, as well as regulates eNOS-VEGF. Tubeimoside I induces cytoprotective Autophagy via an Akt-mediated pathway. Tubeimoside I inhibits proinflammatory cytokine (IL-6 and IL-1β) production. Tubeimoside I exhibits anti-inflammatory activities. Tubeimoside I promotes angiogenesis and improves sepsis symptoms. Tubeimoside I is used in the research of inflammatory diseases, various cancers, sepsis and ischemic diseases.

Isoacteoside is a natural product that can significantly inhibit the formation of glycation end products. Isoacteoside regulates the AKT/PI3K/m-TOR/NF-κB signaling pathway, induces apoptosis in OVCAR-3 cell. Isoacteoside exhibits antitumor, anti-inflammatory, anti-obesity and neuroprotective activities.

Ralimetinib dimesylate (LY2228820 dimesylate) is a selective, ATP-competitive inhibitor of p38 MAPK α/β with IC₅₀s of 5.3 and 3.2 nM, respectively. Ralimetinib (LY2228820) selectively inhibits phosphorylation of MK2 (Thr334), with no effect on phosphorylation of p38a MAPK, JNK, ERK1/2, c-Jun, ATF2, or c-Myc.

Madecassoside is a pentacyclic triterpene isolated from Centella asiatica and has anti-inflammatory properties. Antioxidant and anti-aging effects. Madecassoside is a pentacyclic triterpene isolated from Centella asiatica. Madecassoside is orally active and has inhibitory properties against inflammation, oxidation, apoptosis and autophagy. Madecassosid inhibits activities of p38 MAPK and NF-kB, exhibits an anti-apopototic property, activates Nrf2 expression to reduce the neurotoxicity. Madecassoside can be used in endocrine diseases, cardiovascular diseases, skin diseases and other diseases.

Buloxibutid (AT2 receptor agonist C21) is an orally active, selective angiotensin II type 2 receptor (AT2R) agonist, with a K_i value of 0.4 nM for porcine AT2R. Buloxibutid exerts effects such as vasodilation, anti-inflammation, anti-fibrosis (promoting the expression of collagenase MMP-13) and tissue repair mainly by activating the NO/cGMP pathway, inhibiting the pro-proliferative MAPK signaling, and suppressing the pro-fibrotic TGF-β/Smad pathway as well as the inflammatory NF-κB pathway. Buloxibutid can be used in research related to idiopathic pulmonary fibrosis, hypertension, and systemic sclerosis.

Losmapimod (GSK-AHAB; GW856553X) is an orally active p38α/β MAPK inhibitor, with pK_i values of 8.1 and 7.6 for p38α and p38β, respectively. Losmapimod reduces DUX4 expression, thus exerting efficacy in facioscapulohumeral muscular dystrophy. By inhibiting MAPK/NF-κB, Losmapimod reduces apoptosis of epileptiform hippocampal neurons, and exhibits anti-allodynia and anti-hyperalgesic activities. Losmapimod blocks the entry and fusion of Lassa fever virus (LASV). Losmapimod overcomes tyrosine kinase inhibitor resistance in non-small cell lung cancer (NSCLC). Losmapimod inhibits myocardial senescence and inflammation, and possesses cardioprotective activity against cardiotoxicity.

Neflamapimod (VX-745) is a potent, blood-brain barrier penetrant, highly selective inhibitor of p38α inhibitor with an IC₅₀ for p38α of 10 nM and for p38β of 220 nM. Neflamapimod (VX-745) possesses anti-inflammatory activity.

Afatinib (BIBW 2992) dimaleate is an orally active, potent and irreversible dual specificity inhibitor of ErbB family (EGFR and HER2), with IC₅₀ values of 0.5 nM, 0.4 nM, 10 nM and 14 nM for EGFR^wt, EGFR^L858R, EGFR^L858R/T790M and HER2, respectively. Afatinib dimaleate can be used for the research of esophageal squamous cell carcinoma (ESCC), non-small cell lung cancer (NSCLC) and gastric cancer.

ATN-161 is an antagonist of α5β1 integrin and αvβ3 integrin, as well as an inhibitor of fibrosis, an inhibitor of oxidative stress, a tight junction stabilizer, a mitochondrial integrity protector, an angiogenesis inhibitor and an antiviral agent. ATN-161 inhibits NLRP3, MAPK, and ROS. ATN-161 protects mice from SARS-CoV-2 infection. ATN-161 reduces infarct volume, alleviates edema, decreases immune cell infiltration, reduces the area of choroidal neovascularization lesions, lowers tumor microvessel density and viral load. ATN-161 can be used in research related to ischemic stroke, choroidal neovascularization, breast cancer, coronavirus disease 2019 (COVID-19), and liver metastasis of colorectal cancer.

Darifenacin (UK-88525) hydrobromide is a selective and orally active M3 muscarinic receptor (M3R) antagonist with a pKi of 8.9. Darifenacin hydrobromide binds >20-fold more specifically to M3R than to other muscarinic receptors. Darifenacin hydrobromide can be used in the study of urinary incontinence and other symptoms of overactive bladder. Darifenacin hydrobromide inhibits tumor growth in colorectal cancer cells and has anti-tumor effects.

Darizmetinib (HRX-0215) is an orally active, potent and selective inhibitor of mitogen-activated protein kinase kinase 4 (MKK4). Darizmetinib leads to enhancement of the MKK7 and JNK1 signaling pathways, thereby activating the transcription factors ATF2 and ELK1, promoting cell proliferation and liver regeneration. Darizmetinib is promising for research of preventing liver failure after extensive oncological liver resections or transplantation of small liver grafts.

Esculin is a fluorescent coumarin glucoside, the active ingredient in ash bark. Esculin has antidiabetic effects, improves cognitive impairment in experimental diabetic nephropathy (DN) via the MAPK signaling pathway, and exerts antioxidant stress and anti-inflammatory effects. Esculin also has anticancer, antibacterial, antiviral, neuroprotective, antithrombotic, and therapeutic properties for eye diseases.

Sorafenib-d₃ (Donafenib) is the deuterated-labeled Sorafenib (HY-10201). Sorafenib (Bay 43-9006) is a potent oral active multikinase inhibitor. Sorafenib blocks autophosphorylation and activity of receptor tyrosine kinases (VEGFR-2, VEGFR-3) and RAF family kinases, thereby suppressing the RAF/MEK/ERK and PI3K/Akt pathways, inhibiting STAT3 phosphorylation, and selectively inhibiting the MAPK pathway in cancer cells. Sorafenib induces cell cycle arrest, autophagy, apoptosis, and PARP cleavage, reduces Bcl-2, Bcl-XL, cyclin D1 levels, and activates Bak and Bax. Sorafenib inhibits tumor growth and metastasis in mouse and rat models. Sorafenib can be used for cancer research, such as colon, breast, non-small-cell lung cancer (NSCLC), ovarian, pancreatic, melanoma, colorectal and hepatocellular carcinoma.

Darifenacin (UK-88525) is a selective and orally active M3 muscarinic receptor (M3R) antagonist with a pKi of 8.9. Darifenacin binds >20-fold more specifically to M3R than to other muscarinic receptors. Darifenacin can be used in the study of urinary incontinence and other symptoms of overactive bladder. Darifenacin inhibits tumor growth in colorectal cancer cells and has anti-tumor effects.

Malabaricone C is an orally active and noncompetitive sphingomyelin synthase (SMS) inhibitor with IC₅₀ values of 3 μM and 1.5 μM for SMS 1 and SMS 2, respectively. Malabaricone C reduces body weight gain, improves glucose tolerance, and decreases lipid accumulation in the liver, showing significant prevention of high fat diet-induced fatty liver in mice. Malabaricone C has anti-inflammatory effects, which is found in the fruits of Myristica cinnamomea King. Malabaricone C is promising for research of obesity and immunological disorders caused due to hyper-activation of T-cells.

Exarafenib (RAF/KIN_2787) is an orally-available, selective pan-RAF inhibitor. Exarafenib is effective in RAF-dependent cancers, including all classes of BRAF alterations. Exarafenib suppresses MAPK signaling in RAF-dependent melanoma cell lines. Exarafenib has anticancer activity.

Nitidine chloride, a potential anti-malarial lead compound derived from Zanthoxylum nitidum (Roxb) DC, exerts potent anticancer activity through diverse pathways, including inducing apoptosis, inhibiting STAT3 signaling cascade, DNA topoisomerase 1 and 2A, ERK and c-Src/FAK associated signaling pathway, also has anti-inflammatory activity. Nitidine chloride inhibits LPS-induced inflammatory cytokines production via MAPK and NF-kB pathway.

SB 202190 hydrochloride is a selective p38 MAP kinase inhibitor with IC₅₀s of 50 nM and 100 nM for p38α and p38β2, respectively. SB 202190 hydrochloride binds to the ATP pocket of the active recombinant human p38 kinase with a K_d of 38 nM. SB 202190 hydrochloride has anti-cancer activity. SB202190 hydrochloride induces autophagy.

PF-3644022 is a potent, selective, orally active and ATP-competitive MAPKAPK2 (MK2) inhibitor with an IC₅₀ of 5.2 nM and a K_i of 3 nM. PF-3644022 also inhibits MK3 and p38 regulated/activated kinase (PRAK) with IC₅₀s of 53 nM and 5.0 nM, respectively. PF-3644022 potently inhibits TNFα production and has anti-inflammatory effect.

Dihydrocaffeic acid is a microbial metabolite of flavonoids. Dihydrocaffeic acid scavenges intracellular ROS and increases nitric oxide synthase activity. Dihydrocaffeic acid reduces phosphorylation of MAPK p38 and prevent UVB-induced skin damage. Dihydrocaffeic acid has antioxidant, anti-inflammatory and anti-cartilage degradation activities.