Cyclorasin 9A5 is an 11-residue cell-permeable cyclic peptide that orthosterically inhibits the Ras-Raf protein interaction with an IC50 of 120 nM[1].
p38 Kinase inhibitor 4 (compound 135) is a potent p38 inhibitor[1].
SU3327 is a potent, selective and substrate-competitive JNK inhibitor with an IC50 of 0.7 μM. SU3327 also inhibits protein-protein interactions between JNK and JNK Interacting Protein (JIP) with an IC50 of 239 nM. SU3327 shows less active against p38α and Akt kinase[1][2].
B-Raf IN 9 (compound 8b) is a potent B-Raf inhibitor, with an IC50 of 24.79 nM. B-Raf IN 9 induces apoptosis and shows cell cycle arrest at G2/M phase. B-Raf IN 9 exhibits potent antitumor activity against human prostate cancer PC-3 cell line, with an IC50 of 7.83 µM[1].
MW-150 hydrochloride (MW01-18-150SRM hydrochloride) is a selective inhibitor of p38αMAPK isoform with a ki of 101 nM[1].
JNK-IN-8 is a potent JNK inhibitor with IC50s of 4.7 nM, 18.7 nM, and 1 nM for JNK1, JNK2, and JNK3, respectively.
Withanolide B is an active component of W. somnifera Dunal. Withanolide B promotes osteogenic differentiation of hBMSCs via ERK1/2 and Wnt/β-catenin signaling pathways. Withanolide B exhibits neuroprotective, anti-arthritic, anti-aging and anti-cancer effects[1][2][3].
Urolithin B is one of the gut microbial metabolites of ellagitannins, and has anti-inflammatory and antioxidant effects. Urolithin B inhibits NF-κB activity by reducing the phosphorylation and degradation of IκBα, and suppresses the phosphorylation of JNK, ERK, and Akt, and enhances the phosphorylation of AMPK. Urolithin B is also a regulator of skeletal muscle mass[1][2].
HPK1-IN-12 is potent inhibitor of HPK1. HPK1 is a serine/threonine protein kinase cloned from hematopoietic progenitor cells and belongs to the MAP4K family of mammalian Ste-20-related protein kinases. HPK1-IN-12 has the potential for the research of HPK1 related diseases (extracted from patent WO2021213317A1, compound 85) [1].
GNE-9815 is among the most highly kinase-selective RAF inhibitors targeting KRAS mutant cancers via combination treatment.
Tanzisertib (CC-930) is a potent JNK1/2/3 inhibitor with IC50s of 61/7/6 nM, respectively.
Bisabolangelone, a sesquiterpene derivative, is isolated from the roots of Osterici Radix. Bisabolangelone possesses anti-inflammatory properties, which inhibits LPS-stimulated inflammation through the blocking of NF-kappaB and MAPK pathways in macrophages. Bisabolangelone has anti-ulcer activities[1][2].
CK2/ERK8-IN-1 is a dual casein kinase 2 (CK2) (Ki of 0.25 µM) and ERK8 inhibitor with IC50s of 0.50 μM. CK2/ERK8-IN-1 also binds to PIM1, HIPK2 (homeodomain-interacting protein kinase 2), and DYRK1A with Kis of 8.65 µM, 15.25 µM, and 11.9 µM, respectively. CK2/ERK8-IN-1 has pro-apoptotic efficacy[1].
p38α inhibitor 3 (Comp G7) is a p38α inhibitor that blocks the effectiveness of myoblast differentiation[1].
TC13172 is a mixed lineage kinase domain-like protein (MLKL) inhibitor with an EC50 value of 2 nM for HT-29 cells.
PF-3644022 is a potent, selective, orally active and ATP-competitive MAPKAPK2 (MK2) inhibitor with an IC50 of 5.2 nM and a Ki 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[1].
Antitumor agent-60 (compound 20) is a potent antitumor agent, targeting RAS-RAF signaling pathway and binding to CRAF with a Kd value of 3.93 μM. Antitumor agent-60 induces apoptosis by blocking cell cycle at G2/M phase. Antitumor agent-60 enhances the level of p53 and ROS. Antitumor agent-60 causes oval and irregular nucleus in cancer cells. Antitumor agent-60 can suppress the growth of tumor to some extent in A549 xenograft model[1].
AT7867 dihydrochloride is a potent ATP-competitive inhibitor of Akt1/Akt2/Akt3 and p70S6K/PKA with IC50s of 32 nM/17 nM/47 nM and 85 nM/20 nM, respectively.
p38-α MAPK-IN-4 (Compound 69) is a selective p38α MAPK inhibitor with an IC50 of 1.5 µM. p38-α MAPK-IN-4 rapidly and strongly prevents the development of mechanical allodynia (MA) in vivo[1].
Pamapimod-d4 (Ro4402257-d4) is the deuterium labeled Pamapimod. Pamapimod (Ro4402257) is a potent, selective and orally active p38 MAPK inhibitor with IC50s of 14 nM and 480 nM and Kis of 1.3 nM and 120 nM for p38α and p38β, respectively. Pamapimod has no activity against p38δ or p38γ isoforms. Pamapimod has the potential for rheumatoid arthritis and other autoimmune diseases treatment[1][2].
Bohemine is a purine analogue and is a synthetic and selective CDK inhibitor with IC50s of 4.6 μM, 83 μM, and 2.7 μM for Cdk2/cyclin E, Cdk2/cyclin A, and Cdk9/cyclin T1, respectively. Bohemine also inhibits ERK2 with an IC50 of 52 μM and has less inhibitory effect on CDK1, CDK4 and CDK6. Bohemine has a broad spectrum anti-cancer activities[1][2].
Aspirin (Acetylsalicylic Acid) lithium is an orally active, potent and irreversible inhibitor of cyclooxygenase COX-1 and COX-2, with IC50 values of 5 and 210 μg/mL, respectively. Aspirin lithium induces apoptosis. Aspirin lithium inhibits the activation of NF-κB. Aspirin lithium also inhibits platelet prostaglandin synthetase, and can prevent coronary artery and cerebrovascular thrombosis[1][2][3][4][5][6].
Neflamapimod (VX-745) is a potent and selective inhibitor of p38α, and possesses anti-inflammatory activity.
Andrograpanin, a bioactive compound from Andrographis paniculata, exhibits anti-inflammatory and anti-infectious properties[1][2].
MNK1/2-IN-5 is a potent and selective MNK1/2 inhibitor as a therapeutic agent.
SB-242235 is a potent and selective p38 MAP kinase inhibitor with IC50 of 1.0 uM.IC50 Value: 1.0 uM [1]Target: p38 MAPKin vitro: SB 242235 inhibited intracellular p38 activity, human chondrocytes were treated with different doses of SB 242235 prior to stimulation with IL-1_ for 15 min. MAPKAP K2 was then isolated from these cells and assayed using HSP27 as a substrate. SB 242235 dose-dependently inhibited the activation of MAPKAP K2 with an IC50 of 1.0 uM [1].in vivo: SB-242235 demonstrates generally favourable pharmacokinetic properties in all species examined(including rat, dog and monkey). Systemic plasma clearance was high in rat, but in the non-rodent species SB-242235 demonstrated low to moderate clearance with plasma half-lives > 4h. Oral bioavailability in each preclinical species was high. In rat and monkey, SB-242235 demonstrated non-linear elimination kinetics that manifested as a decrease in clearance with increasing dose and apparent oral bioavailability > 100% at high oral doses [2].In the skin of SKH-1 hairless mice, SB242235, prior to UVB irradiation, blocked activation of the p38 MAPK cascade, and abolished MAPKAPK-2 kinase activity and phosphorylation of HSP27. Moreover, SB242235 inhibited expression of the pro-inflammatory cytokines interleukin (IL)-6 and KC (murine IL-8) and COX-2 [3]. The preclinical pharmacokinetics of SB-242235 have been described previously. The present studies were conducted to describe the in vitro metabolic rates and routes of SB-242235 metabolism, to characterize its in vivo preclinical metabolism, and to use these data to aid in the prediction of the pharmacokinetic behaviour of SB-242235 in man [4].
ERK5-IN-4 (compound 34b) is a potent and selective inhibitor of extracellular signal-related kinase 5 (ERK5). ERK5-IN-4 inhibits ERK5 (full-length) and truncated ERK5 (ERK5 ΔTAD) kinase activity in HEK293 cells with an IC50 of 77 nM and 300 nM, respectively[1].
FMK is a an irreversible RSK2 kinase inhibitor, that covalently modifies the C-terminal kinase domain of RSK.
MK2-IN-3 is a potent and selective inhibitor of MAPKAP-K2 (MK-2), with an IC50 of 8.5 nM. MK2-IN-3 shows selectivity for MK-2 over MK-3, MK-5, ERK2, MNK1, p38a (IC50s=0.21, 0.081, 3.44, 5.7, and >100 μM, respectively) and MSK1, MSK2, CDK2, JNK2, IKK2 (IC50s>200 μM). MK2-IN-3 can reduce TNFα production in both U937 cells and in vivo[1].
Ro 5126766 is a first-in-class dual MEK/RAF inhibitor that allosterically inhibits BRAFV600E, CRAF, MEK, and BRAF (IC50: 8.2, 56, 160 nM, and 190 nM, respectively).