MAPK families play an important role in complex cellular programs like proliferation, differentiation, development, transformation, and apoptosis. In mammalian cells, three MAPK families have been clearly characterized: namely classical MAPK (ERK), C-Jun N-terminal kinse/ stress-activated protein kinase (JNK/SAPK) and p38 kinase. Each MAPK-related cascade consists of no fewer than three enzymes that are activated in series: a MAPK kinase kinase (MAPKKK), a MAPK kinase (MAPKK) and a MAP kinase (MAPK).

The MAPK pathways are activated by diverse extracellular and intracellular stimuli including peptide growth factors, cytokines, hormones, and various cellular stressors. In the ERK signaling pathway, ERK1/2 is activated by MEK1/2, which is activated by Raf. Raf is activated by the Ras GTPase, whose activation is induced by RTKs such as the epidermal growth factor receptor. The JNK and p38 MAPK signaling pathways are activated by various types of cellular stress. The JNK pathway consists of JNK, a MAP2K such as MKK4 (SEK1) or MKK7, and a MAP3K such as ASK1, TAK1, MEKK1, or MLK3. In the p38 pathway, p38 is activated by MKK3 or MKK6, and these MAP2Ks are activated by the same MAP3Ks that function in the JNK pathway.

MAPK signaling pathways has been implicated in the development of many human diseases including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and various types of cancers. Therefore, the development of small molecule drugs that selectively inhibit individual components of MAPK signaling pathways is a key therapeutic strategy for cancer and neurodegenerative disorders.

References:
[1] Zhang W, et al. Cell Research (2002) 12, 9-18.
[2] Kim EK, et al. Biochim Biophys Acta. 2010 Apr;1802(4):396-405.
[3] Kim EK, et al. Arch Toxicol. 2015 Jun;89(6):867-82.


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p38 MAPK-IN-4

p38 MAPK-IN-4 (compound 6) is a p38 MAPK inhibitor with an 50 of 35 nM[1].

  • CAS Number: 219138-24-6
  • MF: C20H13ClFN3O
  • MW: 365.78800
  • Catalog: p38 MAPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bentamapimod

Bentamapimod (AS 602801) is an ATP-competitive JNK inhibitor with IC50 of 80 nM, 90 nM, and 230 nM for JNK1, JNK2, and JNK3, respectively.

  • CAS Number: 848344-36-5
  • MF: C25H23N5O2S
  • MW: 457.547
  • Catalog: JNK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 666.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 356.9±34.3 °C

(Tyr8)-Bradykinin

[Tyr8] Bradykinin is a B2 kinin receptor agonist. [Tyr8] Bradykinin also stimulates ERK1/2 phosphorylation. [Tyr8] Bradykinin can be used as an internal standard[1].

  • CAS Number: 32222-00-7
  • MF: C50H73N15O12
  • MW: 1076.21000
  • Catalog: Bradykinin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GDC-0623

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).

  • CAS Number: 1168091-68-6
  • MF: C16H14FIN4O3
  • MW: 456.210
  • Catalog: MEK
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB203580

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.

  • CAS Number: 152121-47-6
  • MF: C21H16FN3OS
  • MW: 377.435
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 615.6±55.0 °C at 760 mmHg
  • Melting Point: 249 - 250ºC
  • Flash Point: 326.1±31.5 °C

Aza197

AZA197 is a selective small molecule inhibitor of Cdc42.AZA197 suppresses colon cancer cell proliferation, cell migration, invasion and increases apoptosis by down-regulating the PAK1 and ERK signaling pathways in vitro. AZA197 reduces tumor growth and significantly increases mouse survival in SW620 tumor xenografts[1].

  • CAS Number: 1249398-09-1
  • MF: C24H36N6
  • MW: 408.58
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ERK1/2 inhibitor 3

ERK1/2 inhibitor 3 is a potent inhibitor of ERK1/2. Mitogen-activated protein kinase (MAPK) plays an extremely important role in the signal transduction pathway, and extracellular signal regulated kinase (ERK) is a member of the MAPK family. ERK1/2 inhibitor 3 has the potential for the research or prevention of cancer, inflammation or other proliferative diseases (extracted from patent WO2021218912A1, compound 1)[1].

  • CAS Number: 2737294-99-2
  • MF: C28H31ClFN5O6S
  • MW: 620.09
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR/BRAFV600E-IN-1

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].

  • CAS Number: 2492429-45-3
  • MF: C24H24ClN3O3
  • MW: 437.92
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ERK1/2 inhibitor 4

ERK1/2 inhibitor 5 is a potent inhibitor of ERK1/2. Mitogen-activated protein kinase (MAPK) plays an extremely important role in the signal transduction pathway, and extracellular signal regulated kinase (ERK) is a member of the MAPK family. ERK1/2 inhibitor 5 has the potential for the research or prevention of cancer, inflammation or other proliferative diseases (extracted from patent WO2020238776A1)[1].

  • CAS Number: 2490396-99-9
  • MF: C28H31ClFN5O5S
  • MW: 604.09
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Skepinone-L

Skepinone-L is a selective p38 mitogen-activated protein kinase inhibitor. IC50 value:Target: p38MAPKskepinone-L, the first ATP-competitive p38 MAPK inhibitor with excellent in vivo efficacy and selectivity. Therefore, skepinone-L is a valuable probe for chem. biol. research, and it may foster the development of a unique class of kinase inhibitors.

  • CAS Number: 1221485-83-1
  • MF: C24H21F2NO4
  • MW: 425.425
  • Catalog: p38 MAPK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 629.0±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 334.2±31.5 °C

Selonsertib(GS-4997)

Selonsertib is an apoptosis signal-regulating kinase 1 (ASK1) inhibitor with a pIC50 of 8.3±0.07.

  • CAS Number: 1448428-04-3
  • MF: C24H24FN7O
  • MW: 445.492
  • Catalog: MAP3K
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HPK1-IN-16

HPK1-IN-16 is a potent and selective inhibitor of HPK1. Hematopoietic progenitor kinase 1 (HPKl) originally cloned from hematopoietic progenitor cells is a member of MAP kinase kinase kinase kinases (MAP4Ks) family. HPK1-IN-16 is useful in researching, preventing or ameliorating diseases or disorders associated with HPK1 activity such as cancer (extracted from patent WO2019051199A1, compound 39)[1].

  • CAS Number: 2294965-95-8
  • MF: C28H27FN4O
  • MW: 454.54
  • Catalog: MAP4K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TCS JNK 6o

JNK Inhibitor VIII (TCS JNK 6o) is a c-Jun N-terminal kinases (JNK-1, -2, and -3) inhibitor with ki values of 2 nM, 4 nM, 52 nM, respectively[1].

  • CAS Number: 894804-07-0
  • MF: C18H20N4O4
  • MW: 356.38
  • Catalog: JNK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 658.6±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 352.1±31.5 °C

Gypenoside L

Gypenoside L is a saponin that can be found in Gynostemma pentaphyllum. Gypenoside L increases the SA-β-galactosidase activity, promotes the production of senescence-associated secretory cytokines. Gypenoside L also can activate p38 and ERK MAPK pathways and NF-κB pathway to induce senescence. Gypenoside L exhibits anti-tumor and anti-inflammatory activities[1][2].

  • CAS Number: 94987-09-4
  • MF: C42H72O14
  • MW: 801.01
  • Catalog: ERK
  • Density: 1.33±0.1 g/cm3(Predicted)
  • Boiling Point: 912.3±65.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

Licochalcone E

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[1].

  • CAS Number: 864232-34-8
  • MF: C21H22O4
  • MW: 338.4
  • Catalog: p38 MAPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-(2,4-Dihydroxyphenyl)-3-(3-methyl-2-butenyl)-5-hydroxy-8,8-dimethyl-4H,8H-benzo[1,2-b:5,4-b']dipyran-4-one

Cudraflavone B is a prenylated flavonoid with anti-inflammatory and anti-tumor properties. Cudraflavone B is also a dual inhibitor of COX-1 and COX-2. Cudraflavone B blocks the translocation of nuclear factor κB (NF-κB) from the cytoplasm to the nucleus in macrophages. Thus, Cudraflavone B inhibits tumor necrosis factor α (TNFα) gene expression and secretion. Cudraflavone B also triggers the mitochondrial apoptotic pathway, activates NF-κB, the MAPK p38, and ERK, and induced the expression of SIRT1. Thus Cudraflavone B inhibits the growth of human oral squamous cell carcinoma cells[1][2].

  • CAS Number: 19275-49-1
  • MF: C25H24O6
  • MW: 420.45
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NCB-0846

NCB-0846 is an orally available TNIK inhibitor with an IC50 of 21 nM.

  • CAS Number: 1792999-26-8
  • MF: C21H21N5O2
  • MW: 375.432
  • Catalog: MAP4K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

R1487 Hydrochloride

R1487 (Hydrochloride) is highly potent and highly selective inhibitors of p38α.target: p38α;R1487 (Hydrochloride) potently inhibits cytokine production in a variety of in vitro and in vivo models.[1]R1487 (Hydrochloride) inhibits production of TNFR by human monocytic cells (THP-1) and inhibits production of IL-1β in human whole blood (HWB) induced by LPS.[1]

  • CAS Number: 449808-64-4
  • MF: C19H19ClF2N4O3
  • MW: 424.829
  • Catalog: p38 MAPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Astex ERK inhibitor X

ERK1/2 inhibitor 1 is a potent, orally bioavailable ERK1/2 inhibitor, showing 60% inhibition at 1 nM and an IC50 of 3.0 nM against ERK1 and ERK2, respectively[1].

  • CAS Number: 2095719-90-5
  • MF: C29H32ClN5O4
  • MW: 550.05
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AT13148

AT13148 is an orally active and ATP-competitive, multi-AGC kinase inhibitor with IC50s of 38 nM/402 nM/50 nM, 8 nM, 3 nM, and 6 nM/4 nM for Akt1/2/3, p70S6K, PKA, and ROCKI/II, respectively.

  • CAS Number: 1056901-62-2
  • MF: C17H16ClN3O
  • MW: 313.78
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ML-264

ML264 is an antitumor agent that potently and selectively inhibits Krüppel-like factor five (KLF5) expression.

  • CAS Number: 1550008-55-3
  • MF: C17H21ClN2O4S
  • MW: 384.878
  • Catalog: KLF
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 701.0±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 377.7±32.9 °C

ERK5-IN-6

ERK5-IN-6 (compound 5J) is an ERK5 kinase inhibitor with anticancer activity. ERK5-IN-6 exhibits good anti-proliferative activity with the IC50 value of 4.56 µg/mL for A549 cells[1].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Trametiglue

Trametiglue, a derivative of Trametinib (HY-10999), targets both KSR-MEK and RAF-MEK with unprecedented potency and selectivity via unique interfacial binding interactions[1].

  • CAS Number: 2666940-97-0
  • MF: C25H24FIN6O5S
  • MW: 666.46
  • Catalog: MEK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Xantocillin

Xanthocillin is a marine agent extracted from Penicillium commune, induces autophagy through inhibition of the MEK/ERK pathway[1].

  • CAS Number: 580-74-5
  • MF: C18H12N2O2
  • MW: 288.30
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S)-BAY 2965501

(S)-BAY 2965501 is the left-handed isomer of BAY 2965501 (HY-153343). BAY 2965501 is a potent and selective diacylglycerol kinase zeta (DGKζ) inhibitor. BAY 2965501 induces pERK activation. BAY 2965501 can be used for the research of cancer[1].

  • CAS Number: 2732902-09-7
  • MF: C20H19FN4O3S
  • MW: 414.45
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HA-1004

HA-1004 is a selective inhibitor of PKA, which can inhibit lipolysis and induce vascular relaxation. HA-1004 is also a dual inhibitor of cyclic GMP-dependent protein kinase and cyclic AMP-dependent protein, and is involved in smooth muscle, second messenger, cyclic AMP and cyclic GMP regulation mechanisms. HA-1004 can be used as a vasodilator to inhibit the contraction of rabbit aortic strips, or to antagonize ERK and tyrosine hydroxylase (TH) phosphorylation in morphine abstinence rat models[1][2][3].

  • CAS Number: 91742-10-8
  • MF: C12H15N5O2S
  • MW: 293.34
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Isoliquiritin apioside

Isoliquiritin apioside, a component isolated from Glycyrrhizae radix rhizome, 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[1].

  • CAS Number: 120926-46-7
  • MF: C26H30O13
  • MW: 550.509
  • Catalog: p38 MAPK
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 901.0±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 301.9±27.8 °C

TOPK-p38/JNK-IN-1

TOPK-p38/JNK-IN-1 (Compound B12) is an orally active TOPK-p38/JNK signaling pathway inhibitor with the IC50 value of 2.14 µM for NO production. TOPK-p38/JNK-IN-1 shows anti-inflammatory activities. TOPK-p38/JNK-IN-1 also inhibits phosphorylate downstream related proteins and avoids degradation of TOPK[1].

  • CAS Number: 2745108-35-2
  • MF: C17H15F3N2O4
  • MW: 368.31
  • Catalog: JNK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JNJ-49095397

JNJ-49095397 (RV-568) is a specific narrow-spectrum kinase inhibitor that inhibits a selected set of kinases involved in COPD inflammation with IC50 of 5, 40 and 52 nM for p38α, p38γ and HCK, respectively; shows potent anti-inflammatory effects in monocytes and macrophages, demonstrates synergistic interaction in poly I:C-stimulated BEAS-2B cells and in the cigarette smoke model combined with corticosteroid. COPD Phase 2 Clinical

  • CAS Number: 1220626-82-3
  • MF: C34H36N6O4
  • MW: 592.687
  • Catalog: p38 MAPK
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 738.0±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 400.1±32.9 °C

Hu7691

Hu7691 is an orally active, selective Akt inhibitor with IC50s of 4.0 nM, 97.5 nM, 28 nM for Akt1, Akt2 and Akt3, respectively. Hu7691 inhibits tumor growth and enables decrease of cutaneous toxicity in mice[1].

  • CAS Number: 2360523-76-6
  • MF: C22H22ClF3N4O
  • MW: 450.88
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A