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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2-(benzo[d]thiazol-2-yl)-2-(2-chloropyrimidin-4-yl)acetonitrile

JNK-IN-13 (compound 1) is a potent and selective JNK inhibitor with IC50s of 290 nM and 500 nM for JNK3 and JNK2, respectively[1].

  • CAS Number: 345986-38-1
  • MF: C13H7ClN4S
  • MW: 286.74
  • Catalog: JNK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aloisine A

Aloisine A (RP107) is a a potent cyclin-dependent kinase (CDK) inhibitor with IC50s of 0.15 μM, 0.12 μM, 0.4 μM, 0.16 μM for CDK1/cyclin B, CDK2/cyclin A, CDK2/cyclin E, CDK5/p35, respectively. Aloisine A ininhibits GSK-3α (IC50=0.5 µM) and GSK-3β (IC50=1.5 µM). Aloisine A stimulates wild-type CFTR and mutated CFTR, with submicromolar affinity by a cAMP-independent mechanism. Aloisine A has the potential for CFTR-related diseases, including cystic fibrosis research[1][2].

  • CAS Number: 496864-16-5
  • MF: C16H17N3O
  • MW: 267.32600
  • Catalog: CDK
  • Density: 1.227g/cm3
  • Boiling Point: N/A
  • Melting Point: 281-283ºC
  • Flash Point: N/A

(R,S)-CHPG

CHPG is a selective mGluR5 agonist, and attenuates SO2-induced oxidative stress and inflammation through TSG-6/NF-κB pathway in BV2 microglial cells[1]. CHPG protects against traumatic brain injury (TBI) in vitro and in vivo by activation of the ERK and Akt signaling pathways[2].

  • CAS Number: 170846-74-9
  • MF: C8H8ClNO3
  • MW: 201.60700
  • Catalog: mGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Chicanine

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[1].

  • CAS Number: 78919-28-5
  • MF: C20H22O5
  • MW: 342.386
  • Catalog: ERK
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 483.8±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 246.4±28.7 °C

AMG 548

AMG-548 is a potent, oral and selective p38α inhibitor (Ki=0.5 nM), shows slightly selective over p38β (Ki=36 nM) and >1000 fold selective against p38γand p38δ. AMG 548 is also extremely potent in the inhibition of whole blood LPS stimulated TNFα (IC50=3 nM) [1]. AMG-548 inhibits Wnt signaling by direcly inhibing Casein kinase 1 isoforms δ and ε[2].

  • CAS Number: 864249-60-5
  • MF: C29H27N5O
  • MW: 461.55800
  • Catalog: Casein Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EF24

EF24 is a curcumin analogue with greater anti-tumor efficacy and oral bioavailability via deactivation of the MAPK/ERK signaling pathway in oral squamous cell carcinoma (OSCC). EF24 treatment increases the levels of activated caspase 3 and 9, and decreases the phosphorylated forms of MEK1 and ERK[1][2].

  • CAS Number: 342808-40-6
  • MF: C19H16ClF2NO
  • MW: 347.78600
  • Catalog: Caspase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NG25

NG25 is a potent dual TAK1 and MAP4K2 inhibitor, with IC50s of 149 nM and 21.7 nM, respectively.

  • CAS Number: 1315355-93-1
  • MF: C29H30F3N5O2
  • MW: 537.57600
  • Catalog: MAP3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CHMFL-ABL-053

CHMFL-ABL-053 is a potent, selective and orally available Bcr-Abl/Src/p38 kinase inhibitor with IC50 of 70/62/90 nM; no inhibitory activity against c-Kit (>10 uM); inhibits the proliferation of CML cell lines K562 (GI50=14 nM), KU812 (GI50=25 nM), and MEG-01 (GI50=16 nM); completely suppresses tumor progression in the K562 cells inoculated xenograft mouse model with 50 mg/kg/day dosage treatment.

  • CAS Number: 1808287-83-3
  • MF: C28H26F3N7O2
  • MW: 549.547
  • Catalog: p38 MAPK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dehydrocorydaline chloride

Dehydrocorydaline chloride is an alkaloidal that has anti-inflammatory and anti-cancer activities. Dehydrocorydaline chloride can elevate p38 MAPK activation.

  • CAS Number: 10605-03-5
  • MF: C22H24ClNO4
  • MW: 401.88300
  • Catalog: p38 MAPK
  • Density: 1.23g/cm3
  • Boiling Point: 607.6ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 179.9ºC

DCZ19931

DCZ19931 is a potent multi-targeting kinase inhibitor. DCZ19931 has anti-angiogenic effects on ocular neovascularization. DCZ19931 also inhibits ERK1/2-MAPK and p38-MAPK signaling[1].

  • CAS Number: 2789629-84-9
  • MF: C26H20F5N3O5
  • MW: 549.45
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY-2584702 hydrochloride

LY-2584702 hydrochloride is a selective ATP competitive inhibitor of p70S6K with an IC50 of 4 nM. In S6K1 enzyme assay, the IC50 of LY-2584702 is 2 nM.

  • CAS Number: 1082948-81-9
  • MF: C21H20ClF4N7
  • MW: 481.877
  • Catalog: Ribosomal S6 Kinase (RSK)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(5aS,1aS)-5,5aα,6,6aα,7,7aα,7b,7cβ-Octahydro-4,7bβ-dimethyl-6-methylene-3H-cycloprop[2,3]oxireno[4,5]indeno[5,6-b]furan-3-one

Chloranthalactone B, a lindenane-type sesquiterpenoid, is a nature product that could be isolated from Chinese medicinal herb Sarcandra glabra. Chloranthalactone B inhibits the production of inflammatory mediators by inhibiting the AP-1 and p38 MAPK pathways[1].

  • CAS Number: 66395-03-7
  • MF: C15H16O3
  • MW: 244.28600
  • Catalog: COX
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AZD-6244

Selumetinib (AZD6244) is selective, non-ATP-competitive oral MEK1/2 inhibitor, with an IC50 of 14 nM for MEK1. Selumetinib (AZD6244) inhibits ERK1/2 phosphorylation.

  • CAS Number: 943332-08-9
  • MF: C17H17BrClFN4O7S
  • MW: 555.76000
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SEL-201

SLV-2436 is a highly potent and ATP-competitive inhibitor of MNK1 and MNK2 with IC50s of 10.8  nM and 5.4 nM, respectively.

  • CAS Number: 2095704-43-9
  • MF: C19H15ClN4O
  • MW: 350.8
  • Catalog: MNK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

methyllinderone

Methyllinderone is an inhibitor of AP-1/STAT/ERK. Methyllinderone has anti-inflammatory effect. Methyllinderone reduce the invasion and migration rate of TPA-stimulated MCF-7 cells. Methyllinderone can be used in study breast cancer metastasis[1].

  • CAS Number: 3984-73-4
  • MF: C17H16O5
  • MW: 300.31
  • Catalog: STAT
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 570.1±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 254.4±30.2 °C

B-Raf IN 6

B-Raf IN 6 (compound 2c) is a potent inhibitor of protein kinase B-Raf with an IC50 of 1.7 nM. B-Raf IN 6 is devoid of binding to the secondary target PXR and resists rapid metabolism. B-Raf IN 6 has the potential for the research of cancer disease[1].

  • CAS Number: 2648698-34-2
  • MF: C24H21F3N6O2S2
  • MW: 546.59
  • Catalog: Raf
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LGX 818

Encorafenib (LGX818) is a highly potent RAF inhibitor with selective anti-proliferative and apoptotic activity in cells expressing BRAFV600E (EC50=4 nM).

  • CAS Number: 1269440-17-6
  • MF: C22H27ClFN7O4S
  • MW: 540.011
  • Catalog: Raf
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PD184352 (CI-1040)

CI-1040 (PD184352) is an orally active, highly specific, small-molecule inhibitor of MEK with an IC50 of 17 nM for MEK1.

  • CAS Number: 212631-79-3
  • MF: C17H14ClF2IN2O2
  • MW: 478.659
  • Catalog: MEK
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 166-169ºC
  • Flash Point: N/A

Laxiflorin B

Laxiflorin B, a herbal compound, is a novel selective ERK1/2 inhibitor that has antitumor activity[1].

  • CAS Number: 165337-71-3
  • MF: C20H24O5
  • MW: 344.40
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

p38α inhibitor 1

p38α inhibitor 1 is a p38α inhibitor extracted from patent WO 2008076265 A1.

  • CAS Number: 1034189-82-6
  • MF: C22H26F2N4O2
  • MW: 416.46
  • Catalog: p38 MAPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TA-02

TA-02 is a p38 MAPK inhibitor with IC50 of 20 nM.IC50 value: 20 nMTarget: p38TA-02 is a novel compound with similar cardiogenic properties asSB203580 and SB202190. TA-02 especially inhibits TGFBR-2.

  • CAS Number: 1784751-19-4
  • MF: C20H13F2N3
  • MW: 333.334
  • Catalog: p38 MAPK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 515.7±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 265.7±30.1 °C

LUT014

LUT014 is a B-Raf inhibitor with an IC50 of 11.7 nM, extracted from patent WO 2019026065A2 [1].

  • CAS Number: 2274819-46-2
  • MF: C27H19F3N8O
  • MW: 528.49
  • Catalog: Raf
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EVT801

EVT801 is an orally active and selective inhibitor of VEGFR-3 (IC50=11 nM), which has antitumor effects. EVT801 inhibits not only VEGF-C-induced human endothelial cell proliferation, but also tumor (lymphatic) angiogenesis in tumor mouse models. EVT801 can reduce tumor hypoxia, immunosuppressive cytokines (CCL4, CCL5) and myeloid derived suppressor cells (MDSC) production. EVT801 has synergistic effect with immune checkpoint therapy (ICT), which improves ICT response rate and has better inhibitory effect on cancer mouse models[1].

  • CAS Number: 1412453-70-3
  • MF: C19H21N5O3
  • MW: 367.40
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Diprovocim

Diprovocim is a potent Toll-like receptor TLR1/TLR2 agonist that induces dose-dependent TNF production with EC50 of 110 pM in human THP-1 cells and 1.3 nM in primary mouse peritoneal macrophages; induces TNF production in bone marrow-derived dendritic cells (BMDC) with EC50 of 6.7 nM, also induces IL-6 production by mouse BMDC; induces phosphorylation of IKKα, IKKβ, p38, JNK, and ERK, as well as degradation of IκBα in THP-1 cells and mouse peritoneal macrophages, activates conventional TLR1/TLR2 signaling, including MAPK and canonical NF-κB signaling; synergizes with anti-PD-L1 to eliminate melanoma in mice.

  • CAS Number: 2170867-89-5
  • MF: C56H56N6O6
  • MW: 909.1
  • Catalog: Toll-like Receptor (TLR)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nedometinib

Nedometinib is a tyrosine kinase inhibitor targeting to MEK1. Nedometinib has antineoplastic effect and can be used for research in dermatosis, cutaneous fibroneuroma, neurofibromatosis[1].

  • CAS Number: 2252314-46-6
  • MF: C17H16FIN4O3
  • MW: 470.24
  • Catalog: MEK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pexmetinib

Pexmetinib is a potent Tie-2 and p38 MAPK dual inhibitor, with IC50s of 1 nM, 35 nM and 26 nM for Tie-2, p38α and p38β, respectively, and can be used in the research of acute myeloid leukemia.

  • CAS Number: 945614-12-0
  • MF: C31H33FN6O3
  • MW: 556.630
  • Catalog: p38 MAPK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 694.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 373.6±31.5 °C

Pamoic acid disodium

Pamoic acid disodium is a potent GPR35 agonist with an EC50 value of 79 nM. Pamoic acid disodium induces GPR35 internalization and activates ERK1/2 with EC50 values of 22 nM and 65 nM, respectively. Pamoic acid disodium potently recruits β-arrestin2 to GPR35 and has an antinociceptive effect[1].

  • CAS Number: 6640-22-8
  • MF: C23H14Na2O6
  • MW: 432.333
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: 642.7ºC at 760 mmHg
  • Melting Point: 300 °C
  • Flash Point: 356.5ºC

TA-01

TA-01 is a potent CK1 and p38 MAPK inhibitor, with IC50s of 6.4 nM, 6.8 nM, 6.7 nM for CK1ε, CK1δ and p38 MAPK, respectively.

  • CAS Number: 1784751-18-3
  • MF: C20H12F3N3
  • MW: 351.325
  • Catalog: Casein Kinase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 511.1±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 262.9±30.1 °C

lucidone

Lucidone, an anti-inflammatory agent that can be isolated from the fruit of Lindera erythrocarpa Makino. Lucidone inhibits LPS-induced NO and PGE2 production in RAW 264.7 mouse macrophages. Lucidone also decreases TNF-α secretion, iNOS and COX-2 expression. Lucidone prevents NF-κB translocation and inhibits JNK and p38MAPK signals. Lucidone also has inhibitory activity against Dengue virus (DENV) (EC50=25 μM)[1][2].

  • CAS Number: 19956-53-7
  • MF: C15H12O4
  • MW: 256.253
  • Catalog: COX
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 489.6±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 188.6±22.2 °C

YL5084

YL5084, a covalent JNK inhibitor, exhibits selectivity for JNK2 and JNK3 over JNK1 with IC50s of 70 nM, 84 nM and 2173 nM, respectively. YL5084 exhibits JNK2-independent antiproliferative effects and induces apoptosis in a JNK2-independent manner[1].

  • CAS Number: 2440199-73-3
  • MF: C35H36N8O2
  • MW: 600.71
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A