p38

SJFα is a 13-atom linker PROTAC based on von Hippel-Lindau ligand. SJFα degrades p38α with a DC50 of 7.16nM, but is far less effective at degrading p38δ (DC50=299nM) and does not degrade the other p38 isoforms (β and γ) at concentrations up to 2.5μM.

SJFδ is a 10-atom linker PROTAC based on von Hippel-Lindau ligand. SJFδ degrades p38δ with a DC50 of 46.17nM, but does not degrade p38α, p38β, or p38γ.

Rehmannioside A is an inhibitor of cytochrome P450 enzymes (CYP3A4, 2C9, and 2D6), with IC 50 values of 10.08, 12.62, and 16.43μM, respectively.

Talmapimod (SCIO-469) (SCIO-469) is an orally active, selective, and ATP-competitive p38α inhibitor with an IC50 of 9 nM. Talmapimod (SCIO-469) shows about 10-fold selectivity over p38β, and at least 2000-fold selectivity over a panel of 20 other kinases, including other MAPKs.

MW-150 dihydrochloride dihydrate (MW01-18-150SRM dihydrochloride dihydrate) is a selective, CNS penetrant, and orally active inhibitor of p38α MAPK with a Ki of 101 nM.

4-Hydroxylonchocarpin is a chalcone compound from an extract of Psoralea corylifolia.

Bisabolangelone, a sesquiterpene derivative, is isolated from the roots of Osterici Radix.

Chicanine is a lignan compound of Schisandra chinesis, inhibits LPS-induced phosphorylation of p38 MAPK, ERK 1/2 and IκB-α, with anti-inflammatory activity.

An alkaloid with diverse biological activities

FTI 276 TFA is a protein farnesyl transferase (PFT) inhibitor with an IC 50 value of 1nM.

Licochalcone E, a flavonoid compound isolated from Glycyrrhiza inflate, inhibits NF-κB and AP-1 transcriptional activity through the inhibition of AKT and MAPK activation.

Paris saponin VII (Chonglou Saponin VII) is a steroidal saponin isolated from the roots and rhizomes of Trillium tschonoskii Maxim. Paris saponin VII-induced apoptosis in K562/ADR cells is associated with Akt/MAPK and the inhibition of P-gp. Paris saponin VII attenuates mitochondrial membrane potential, increases the expression of apoptosis-related proteins, such as Bax and cytochrome c, and decreases the protein expression levels of Bcl-2, caspase-9, caspase-3, PARP-1, and p-Akt. Paris saponin VII induces a robust autophagy in K562/ADR cells and provides a biochemical basis in the treatment of leukemia.

SB-242235 is a potent and selective p38 MAP kinase inhibitor, with an IC50 of 1.0 μM in primary human chondrocytes.

SKF-86002 is an orally active p38 MAPK inhibitor, with anti-inflammatory, anti-arthritic and analgesic activities.

Dihydrocaffeic acid is a phenolic acid found in Gynura bicolor, reduces phosphorylation of MAPK p38 and prevent UVB-induced skin damage.

AMG-548 dihydrochloride, an orally active and selective p38α inhibitor (Ki=0.5 nM), shows slightly selective over p38β (Ki=36 nM) and >1000 fold selective against p38γ and p38δ.

Rotundic acid, a triterpenoid obtained from I.

A flavonoid with diverse biological activities

Isoliquiritin apioside significantly decreases PMA-induced increases in MMP9 activities and suppresses PMA-induced activation of MAPK and NF-κB. Isoliquiritin apioside auppresseses invasiveness and angiogenesis of cancer cells and endothelial cells.

A dual inhibitor of p38α and p38β MAPKs

Semapimod tetrahydrochloride (CNI-1493), an inhibitor of proinflammatory cytokine production, can inhibit TNF-α, IL-1β, and IL-6.

Ferulic acid is a hydroxycinnamic acid that is abundant in plants and originally derived from giant fennel (F.

Inflachromene is an inhibitor of HMGB1 and HMGB expression. Inflachromene can inhibit the release of HMGB1 and the NF-κB signaling pathway, exerting anti-inflammatory and neuroprotective effects. Inflachromene is mainly used to treat epilepsy.