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p38 mitogen-activated protein kinase (MAPK) inhibitors act on stress-activated kinases of the MAPK family. In 1994 p38 was described as a kinase phosphorylated on tyrosine after exposure of cells to bacterial endotoxin or hyperosmolarity. In the same year, a kinase targeted by pyridinyl imidazole compounds was shown to regulate the biosynthesis of inflammatory cytokines. Adezmapimod, also known as SB 203580, and SB 202190 belong to this pyridinyl imidazole class and inhibit p38α and p38β. Doramapimod binds an allosteric pocket that becomes accessible in an inactive conformation of the kinase, a binding mode reported in 2002. PH-797804 and ralimetinib dimesylate are further p38α inhibitors for studies of inflammatory and stress signaling.
Ganoderterpene A is a potent inhibitor of p38 MAPK, demonstrating significant anti-inflammatory and anti-apoptotic activity. It effectively attenuates LPS-induced inflammation and apoptosis by suppressing the MAPK and TLR-4/NF-κB signaling pathways in BV-2 cells. This compound is valuable for research applications focused on neuroinflammation and cellular stress responses.
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2-Stearoxyphenethyl phosphocholin is a potent inhibitor of p38 MAPK, a key regulator of inflammatory and stress response pathways. This compound demonstrates significant anticancer activity and may selectively interact with the lipid-binding pocket of p38 MAPK, influencing its function. Due to its broad-spectrum anti-tumor properties and lipid-modulating effects, it is applicable in cancer research and studies focused on metabolic regulation.
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p38-α MAPK-IN-5 is a potent inhibitor of p38α MAPK, exhibiting competitive affinity with an IC50 of 0.1 nM against p38α, and 0.2 nM for p38β, while displaying reduced efficacy toward p38γ and p38δ. This compound demonstrates significant anti-inflammatory properties, making it a valuable tool for researching inflammatory pathways associated with conditions such as asthma and chronic obstructive pulmonary disease (COPD). Its specificity for p38α underscores its potential utility in studies aimed at elucidating the role of this kinase in inflammatory responses and related therapeutic interventions.
BIRB-1017 is a selective inhibitor of p38 MAP kinase, a key regulator in the inflammatory response. It demonstrates significant biological activity by modulating cytokine production and cellular signaling pathways associated with inflammation. This compound is suitable for use in research focused on understanding p38 signaling in various inflammatory diseases and therapeutic interventions.
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p38 MAPK-IN-10 is a potent inhibitor of p38 MAP kinase, exhibiting an IC50 of 570 nM. This orally active compound shows promise in the study of chronic inflammatory diseases, including rheumatoid arthritis and Crohn’s disease. Its mechanism of action targets the p38 MAPK signaling pathway, making it a valuable tool for researchers investigating therapeutic approaches to modulate inflammation.
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R-130823 is a highly selective p38α inhibitor that exhibits an IC50 of 22 nM specifically against p38α, with minimal activity towards p38β (IC50 of 820 nM) and no significant interaction with p38γ or p38δ. This compound effectively downregulates cartilage degradation and inflammatory mediators, including the inhibition of MMP-13, MMP-1, and PGE2 release. R-130823 demonstrates therapeutic potential in reducing hind paw swelling, alleviating hyperalgesia, and impeding the progression of arthritis. It is particularly relevant for research studies focusing on osteoarthritis and rheumatoid arthritis.
p38 Kinase Inhibitor 5 (AA6) selectively targets p38 MAP kinase, exhibiting a potent inhibitory effect with an IC50 of 403.57 nM. This compound is known for its significant anti-inflammatory activity, making it a valuable tool for research in inflammatory disease models and studies related to cytokine signaling pathways. Its role in modulating p38 kinase activity can provide insights into the mechanistic understanding of various pathological conditions.
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CBS-3595 is a dual inhibitor of p38 MAP kinase and phosphodiesterase 4, exhibiting potent anti-inflammatory and anti-allodynic effects. This compound significantly decreases the production of the proinflammatory cytokine IL-6 while elevating levels of the anti-inflammatory cytokine IL-10 in rat models. Additionally, CBS-3595 effectively mitigates paw edema in the Complete Freund’s adjuvant-induced arthritis model, making it a valuable tool for investigating potential therapies for autoimmune diseases.
p38α inhibitor 7 is a potent inhibitor of the p38α mitogen-activated protein kinase, a key regulator of inflammation and stress responses. This compound demonstrates significant biological activity by effectively modulating the p38α pathway, making it applicable in studies exploring inflammatory diseases and neurological disorders. Its favorable pharmacokinetic properties enhance its potential for oral administration in therapeutic research.
AW-814141 is a selective and orally active inhibitor of p38 MAP kinase, demonstrating IC50 values of 100 nM for p38-α and 158 nM for p38-β isoforms. This compound effectively reduces TNF-α production induced by LPS and demonstrates a dose-dependent inhibition of paw edema in rat models. AW-814141 serves as a valuable tool in studying anti-inflammatory mechanisms and has potential applications in researching inflammatory diseases, including rheumatoid arthritis.
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Synonyms: MW01-11-108SRM hydrochloride
MW108 hydrochloride is a selective inhibitor of p38α MAPK, with an affinity (Ki) of 114 nM. This compound demonstrates the ability to mitigate beta-amyloid-induced synaptic impairments and cognitive dysfunction, making it a valuable tool for studying neurodegenerative disorders. Its central nervous system penetration enhances its utility in research focused on Alzheimer's disease and related pathologies.
p38α-MK2-IN-1 is a potent inhibitor of the p38α-MK2 complex, demonstrating an IC50 of 5 nM. This compound exhibits significant anti-inflammatory properties and promotes joint repair, making it a valuable tool for studies focused on inflammation and regenerative medicine. Researchers can employ p38α-MK2-IN-1 in various applications, including drug discovery and the exploration of signaling pathways related to inflammatory responses.
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p38 Kinase-IN-9 is a potent p38 kinase inhibitor characterized by an IC50 of less than 1 μM. This compound is valuable for investigating the role of p38 kinase in various diseases, particularly those related to inflammation. It serves as a useful tool for research applications aimed at understanding the mechanistic pathways of p38-mediated disorders.
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p38α-IN-9 is a potent p38α inhibitor that effectively suppresses the enzymatic activity of p38α with an IC50 value below 20 nM. This compound inhibits MK2T334 phosphorylation, resulting in the activation of Cdc25b and Cdc25c, while concurrently inactivating Wee1. The modulation of these pathways induces mitotic catastrophe, aneuploidy, and polyploidy, contributing to DNA damage. p38α-IN-9 is particularly relevant in studies of colorectal cancer metastasis.
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(aS)-PH-797804 is a selective inhibitor of p38 MAPK, demonstrating IC50 values of 26 nM for p38 α and 102 nM for p38 β. This compound exhibits significant anti-inflammatory activity, making it a valuable tool for research applications focused on inflammatory signaling pathways and related disease models. Its specificity towards p38 MAPK allows for the exploration of its role in cellular processes and therapeutic interventions in conditions associated with p38 MAPK dysregulation.
p38α inhibitor 3 is a selective p38α inhibitor that impedes myoblast differentiation. By targeting the p38 MAPK pathway, this compound plays a crucial role in modulating cellular responses associated with inflammation and stress. Its applications include studying muscle development and cellular signaling processes in various research contexts.
p38 MAP Kinase-IN-2 is a potent inhibitor of the p38 MAP Kinase pathway, primarily involved in cellular stress responses and inflammation. This compound demonstrates significant inhibitory activity, making it valuable for cancer research and the investigation of various inflammatory diseases. Its mechanism and efficacy provide a useful tool for studying the role of p38 MAP Kinase in cellular processes and therapeutic applications.
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RPR-200765A methanesulfonate is a potent inhibitor of p38 MAPK, demonstrating an IC50 of 0.050 μM. This compound selectively targets the p38 MAPK pathway while showing minimal activity against Lck, ERK, ZAP70, and SYK. RPR-200765A methanesulfonate effectively inhibits TNFα production, making it a valuable tool for investigating inflammatory diseases and related cellular processes.
BMS-626531 is a selective inhibitor of p38α MAP kinase, demonstrating potent activity against this important signaling pathway. This compound has been shown to effectively modulate cellular responses associated with inflammation and stress, making it a valuable tool in cancer research. Its ability to inhibit p38α MAP kinase renders it useful for investigating mechanisms of tumor progression and potential therapeutic applications in oncology.
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p38-α MAPK-IN-6 is a selective inhibitor of the p38α mitogen-activated protein kinase (MAPK). This compound modulates inflammatory responses by inhibiting the activation of p38 MAPK, a key regulator in cellular stress signaling pathways. It is useful in research applications focused on studying inflammatory diseases, neurodegeneration, and cancer biology.
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p38 MAP Kinase-IN-3 is a potent inhibitor of p38 MAP kinase, exhibiting an IC50 value of 0.09 µM. This compound plays a significant role in modulating inflammatory and stress responses, making it a valuable tool for studying metabolic disorders and related pathways. Its specific inhibition of the p38 MAP kinase pathway allows for detailed investigation into its role in various biological processes and disease mechanisms.
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Synonyms: Methyl 3,5-dicaffeoyl quinic acid
Macranthoin G is a selective inhibitor of p38 MAPK, a critical signaling pathway involved in stress responses. This compound demonstrates protective effects against cytotoxicity induced by amyloid-beta (Aβ) and hydrogen peroxide in neuronal cells by downregulating p38 MAPK activity. Macranthoin G is a valuable tool for research applications related to neurodegenerative diseases, particularly Alzheimer’s Disease.
p38 MAPK-IN-8 is a potent and selective inhibitor of p38 mitogen-activated protein kinase (p38 MAPK). It exhibits strong oral bioavailability, making it an ideal candidate for in vivo studies. This compound is valuable for investigating inflammatory responses, autoimmune disorders, and various cancer pathways, facilitating a deeper understanding of these complex biological processes.
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ARRY-371797 is a potent and orally bioavailable inhibitor of p38α MAPK and butyrylcholinesterase (BChE), demonstrating IC50 values of 12.0 µM for p38α MAPK and 0.13 µM for BChE, with minimal activity against human acetylcholinesterase (hAChE). This compound shows promise for research applications in Alzheimer’s disease, particularly in the context of neuroinflammation and cholinergic system modulation.
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p38 MAPK-IN-7 is a selective inhibitor of p38 MAP kinase, exhibiting an IC50 value of 170 nM. This compound demonstrates potent inhibition of p38 MAPK activity, making it a valuable tool for investigating the role of this kinase in various inflammatory diseases, including rheumatoid arthritis and septic shock. Its oral bioavailability enhances its potential for in vivo studies aimed at understanding the therapeutic implications of p38 MAPK modulation.
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