p38 Kinase inhibitor 4 (compound 135) is a potent p38 inhibitor[1].
MW-150 hydrochloride (MW01-18-150SRM hydrochloride) is a selective inhibitor of p38αMAPK isoform with a ki of 101 nM[1].
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].
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.
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].
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].
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].
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.
LJI308 is a new and potent pan-RSK inhibitor, with IC50 of 6 nM, 4 nM, and 13 nM for RSK1, RSK2, and RSK3, respectively.IC50 value: 6/4/13 nMTarget: RSK1/2/3in vitro: LJI308 efficiently inhibits RSK activity. LJI308 inhibites S6K1 with an IC50 of 0.8 μM, representing a 200-fold lower inhibition than that of RSK2. LJI308 inhibits MEK4 less than 50% at 10 μMand HIP kinase 1 less than 50% at 1 μM. [1] LJI308 inhibits the growth and survival of TNBC. LJI308 also suppresses the growth of HTRY-LT cells in 3-dimensional soft agar cultures. LJI308 is one of the first potent and effective targeted therapies for TNBC that, unlike currently utilized drugs, exhibits efficacy in eliminating the CSC population. [2]
ASK1-IN-5 (S-99) is an inhibitor of apoptosis signal-regulated kinase 1 (ASK1) and is useful in the study of autoimmune and neurodegenerative diseases[1].
POP-3MB (compound 1b) is an ICMT inhibitor (IC50: 2.5 μM). POP-3MB changes the subcellular localization of K-Ras and inhibits Ras activation. POP-3MB also inhibits Erk phosphorylation[1].
Cobimetinib (GDC-0973, RG7420) is a potent, selective and oral MEK inhibitor with an IC50 of 4.2 nM for MEK1.
Sorafenib (Bay 43-9006) is a potent multikinase inhibitor with IC50s of 6 nM, 20 nM, and 22 nM for Raf-1, B-Raf, and VEGFR-3, respectively.
Pluripotin is a dual inhibitor of ERK1 and RasGAP with KDs of 98 nM and 212 nM, respectively. Pluripotin also inhibits RSK1, RSK2, RSK3, and RSK4 with IC50s of 0.5, 2.5, 3.3, and 10.0 µM, respectively.
Emodic acid (NSC624610) is an anthraquinone compound isolated from A. microcarpus, which can inhibit the proliferation of cancer cells by inhibiting the activity of NF-κB. Emodic acid can also inhibit the phosphorylation of p38, ERK and JNK, the secretion of tumor-promoting cytokines IL-1β and IL-6, and the expression of VEGF and MMP, thereby inhibiting the invasion and migration potential of cancer cells[1].
CMK is a RSK2 kinase inhibitor which exhibits similar potency but less chemical stability compared with FMK.
BRAF V600E/CRAF-IN-2 (Compound 9c) is a potent inhibitor of BRAF V600E/CRAF with IC50s of 0.888 and 0.229 μM, respectively. BRAF V600E/CRAF-IN-2 triggers apoptosis and cell cycle arrest at G0/G1 phase in HCT-116 colon cancer cell. BRAF V600E/CRAF-IN-2 has the potential for the research of cancer diseases[1].
AD57 hydrochloride is an orally active multikinase inhibitor, inhibits RET, BRAF, S6K and Src[1].
TAK-733 is a potent and selective MEK allosteric site inhibitor with an IC50 of 3.2 nM.
BMS-582949 hydrochloride is a novel highly selective p38α MAPK inhibitor, inhibits p38α with IC50 of 13 nM. IC50 value: 13 nM[1]Target: p38αin vitro: BMS-582949 does not significantly inhibit cytochrome P450 isozymes 1A2, 2C9, 2C19, and 2D6 with IC50values >40 μM. It is a weak inhibitor of CYP3A4, with an IC50 value ranging from 18 to 40 μM based in multiple tests. BMS-582949 displays >2000-fold selectivity for p38α over a diverse panel of 57 kinases that include serine kinases, nonreceptor tyrosine kinases, receptor tyrosine kinases, and the p38γ and δ isoforms. BMS-582949 is also 450-fold selective over Jnk2, a MAP kinase involved in inflammation, and 190-fold selective over Raf[1].BMS-582949 is a novel highly selective p38α MAPK inhibitor [2]. in vivo: The mouse clearance rate for BMS-582949 is 4.4 mL/min/kg. And, at an oral dose of 10 mg/kg, the mouse AUC0?8 h for BMS-582949 is 75.5 μM·h. BMS-582949 exhibited oral bioavailability values of 90% and 60% in mice and rats, respectively[1].
ERK-IN-7 (Example 10), an analogue of SHR2415 (HY-151367), is a potent ERK inhibitor with IC50 of 5 nM and 7 nM against ERK1 and ERK2, respectively[1].
L-threo-Sphingosine is a potent MAPK inhibitor. L-threo-Sphingosine induces apoptosis and clear DNA fragmentation. L-threo-Sphingosine shows anticancer effect[1].
IQ-1 is a prospective inhibitor of NF-κB/activating protein 1 (AP-1) activity with an IC50 of 2.3±0.41 μM. IQ-1 has binding affinity (Kd values) in the nanomolar range for all three JNKs with Kds of 100 nM, 240 nM, and 360 nM for JNK3, JNK1, and JNK2, respectively.
XMD8-92 is a highly selective ERK5/BMK1 inhibitor with dissociation constant (Kd) value of 80 nM.
GDC-0623 is a potent, ATP-uncompetitive inhibitor of MEK1 (Ki=0.13 nM, +ATP), and displays 6-fold weaker potency against HCT116 (KRAS (G13D), EC50=42 nM) versus A375 (BRAFV600E, EC50=7 nM).
SB 203580 is a widely used p38 MAPK inhibitor with an IC50 of 0.3-0.5 μM. It shows more than 100-fold selectivity over PKB, LCK, and GSK-3β.
EGFR/BRAFV600E-IN-1 (Compound 23) is a potent EGFR and BRAFV600E dual inhibitor with IC50s of 0.08 and 0.15 µM, respectively. EGFR/BRAFV600E-IN-1 induces apoptosis and cell cycle arrest in both pre-G1 and G2/M phases. EGFR/BRAFV600E-IN-1 exhibits antiproliferative activity againist A-549, MCF-7, Panc-1, HT-29 with IC50s of 1.2, 0.79, 1.3, and 1.23 µM, respectively[1].