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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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

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

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

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

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

S6K-18

S6K-18 is a potent and selective p70S6K1 inhibitor with an IC50 of 52 nM[1].

  • CAS Number: 1265789-88-5
  • MF: C17H18N4O3S
  • MW: 358.41
  • Catalog: Ribosomal S6 Kinase (RSK)
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 494.9±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 253.1±28.7 °C

SR-3737

SR-3737 is potent both JNK3 and p38 inhibitor.

  • CAS Number: 1164153-37-0
  • MF: C29H25FN4O4
  • MW: 512.53
  • Catalog: JNK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MKK7-COV-9

MKK7-COV-9 is a potent and selective covalent inhibitor of MKK7 and targets a specific protein–protein interaction of MKK7. MKK7-COV-9 blocks primary B cell activation in response to LPS with an EC50 of 4.98 μM[1].

  • CAS Number: 2283355-59-7
  • MF: C18H16N4O2
  • MW: 320.35
  • Catalog: p38 MAPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RET-IN-19

RET-IN-19 (compound 59) is a potent RET inhibitor, with IC50 values of 6.8 and 13.51 nM against RET-wt and RET V804M, respectively. RET-IN-19 shows anticancer activity. RET-IN-19 can be used for non-small cell lung cancer (NSCLC) research[1].

  • CAS Number: 2484919-71-1
  • MF: C28H28N6O4S
  • MW: 544.62
  • Catalog: Aurora Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GW806742X

GW806742X is a Mixed Lineage Kinase Domain-Like (MLKL) inhibitor which binds the MLKL pseudokinase domain with a Kd value of 9.3 μM and anti-necroptosis activity. GW806742X has activity against VEGFR2[1][2].

  • CAS Number: 579515-63-2
  • MF: C25H22F3N7O4S
  • MW: 573.55
  • Catalog: Mixed Lineage Kinase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1-Vinyl-4-methoxy-β-carboline

Dehydrocrenatidine, a β-carboline alkaloid that can be isolated from Picrasma quassioides. Dehydrocrenatidine induces cell Apoptosis by activates ERK and JNK. Dehydrocrenatidine inhibits invasion and migration of cancer cells, it also suppresses neuronal excitability to exert analgesic effects[1][2].

  • CAS Number: 26585-13-7
  • MF: C14H12N2O
  • MW: 224.258
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 461.2±40.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 151.1±17.0 °C

Pamoic acid

Pamoic acid is a potent GPR35 agonist with an EC50 of 79 nM. Pamoic acid exhibits neuroprotective and anti-inflammatory properties[1][2].

  • CAS Number: 130-85-8
  • MF: C23H16O6
  • MW: 388.38
  • Catalog: ERK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 642.7±55.0 °C at 760 mmHg
  • Melting Point: ≥300 °C (dec.)
  • Flash Point: 356.5±28.0 °C

Enniatin A1

Enniatin A1 isolated from Fusarium mycotoxins is a cyclic hexadepsipeptide consisting of alternating D-α-hydroxyisovaleric acids and N-methyl-L-amino acids. Enniatin A1 possesses anticarcinogenic properties by induction of apoptosis and disruption of ERK signalling pathway. Enniatin A1 inhibits ACAT with an IC50 of 49 μM in rat liver microsomes[1].

  • CAS Number: 4530-21-6
  • MF: C35H61N3O9
  • MW: 667.87400
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Astragaloside IV

Astragaloside IV, an active component isolated from Astragalus membranaceus, suppresses the activation of ERK1/2 and JNK, and downregulates matrix metalloproteases (MMP)-2, (MMP)-9 in MDA-MB-231 breast cancer cells.

  • CAS Number: 84687-43-4
  • MF: C41H68O14
  • MW: 784.970
  • Catalog: ERK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 895.7±65.0 °C at 760 mmHg
  • Melting Point: 295-296ºC
  • Flash Point: 495.5±34.3 °C

BI-D1870

BI-D1870 is an ATP-competitive inhibitor of RSK isoforms, with IC50s of 31 nM/24 nM/18 nM/15 nM for RSK1/SK2/SK3/SK4, respectively.

  • CAS Number: 501437-28-1
  • MF: C19H23F2N5O2
  • MW: 391.415
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 579.3±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 304.2±32.9 °C

CYCLOARTENOL

Cycloartenol, a phytosterol compound, is one of the key precusor substances for biosynthesis of numerous sterol compounds. Cycloartenol inhibits the migration of glioma cells and suppresses the phosphorylation of the p38 MAP kinase. Cycloartenol has a variety of pharmacological activities such as anti-inflammatory, anti-tumor, antioxidant, antibiosis and anti-alzheimer's disease. Cycloartenol also plays an important role in the process of plant growth and development[1][2].

  • CAS Number: 469-38-5
  • MF: C30H50O
  • MW: 426.71700
  • Catalog: Apoptosis
  • Density: 1.01 g/cm3
  • Boiling Point: 505.5ºC at 760 mmHg
  • Melting Point: 115-117ºC
  • Flash Point: 221.9ºC

AS703026

Pimasertib (AS703026) is a highly selective, potent, ATP non-competitive allosteric inhibitor of MEK1/2, used for cancer treatment.

  • CAS Number: 1236699-92-5
  • MF: C15H15FIN3O3
  • MW: 431.201
  • Catalog: MEK
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: 623.2±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 330.7±31.5 °C

OVA-E1 peptide

OVA-E1 peptide, is an antagonist variant of SIINFEKL [OVA (257-264). OVA-E1 peptide, activates the p38 and JNK cascades similarly in mutant and wild-type thymocytes[1].

  • CAS Number: 153316-01-9
  • MF: C47H76N10O14
  • MW: 1005.16
  • Catalog: JNK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CEP-32496

CEP-32496 is a highly potent and orally efficacious inhibitor of BRAFV600E with a Kd of 14 nM.

  • CAS Number: 1188910-76-0
  • MF: C24H22F3N5O5
  • MW: 517.45700
  • Catalog: Raf
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BRD-7389

BRD7389 is a specific RSK family kinase inhibitor with IC50s of 1.5 μM, 2.4 μM, and 1.2 μM for RSK1, RSK2, and RSK3, respectively. BRD7389 is a small-molecule inducer of insulin expression in pancreatic α-cells[1].

  • CAS Number: 376382-11-5
  • MF: C24H18N2O2
  • MW: 366.41200
  • Catalog: Ribosomal S6 Kinase (RSK)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

peruvoside

Peruvoside is a potent inhibitor of Src, PI3K, JNK, STAT, and EGFR. Peruvoside induces apoptosis and autophagy and possesses a broad spectrum of anticancer activity in breast, lung, liver cancers and leukemia. Peruvoside is a broad-spectrum and potent antiviral activity against positive-sense RNA viruses. Peruvoside sensitizes Gefitinib (HY-50895)-resistant tumour cells (A549, PC9/gef and H1975) to Gefitinib[1][2][3][4].

  • CAS Number: 1182-87-2
  • MF: C30H44O9
  • MW: 548.66
  • Catalog: Apoptosis
  • Density: 1.31g/cm3
  • Boiling Point: 731.6ºC at 760 mmHg
  • Melting Point: 161-164ºC
  • Flash Point: 236.2ºC

MEK-IN-5

MEK-IN-5 is a potent MEK inhibitor and NO donor. MEK-IN-5 significantly reduces the levels of pMEK and pERK in a dose-dependent and time-dependent manner. MEK-IN-5 induces apoptosis in MDA-MB-231 cells[1].

  • CAS Number: 2417022-06-9
  • MF: C29H27FN4O10S2
  • MW: 674.67
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TL4-12

TL4-12 is a selective MAP4K2/GCK inhibitor, dose-dependently downregulates IKZF1 and BCL-6 and leads to MM cell proliferation inhibition (IC50=37 nM) accompanied by induction of apoptosis. TL4-12 can be used to overcome immunomodulatory drug resistance in multiple myeloma (MM)[1].

  • CAS Number: 1620820-12-3
  • MF: C25H27F3N6O2
  • MW: 500.516
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 586.8±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 308.7±30.1 °C

Enniatin B

Enniatin B is a Fusarium mycotoxin. Enniatin B inhibits acyl-CoA: cholesterol acyltransferase (ACAT) activity with an IC50 of 113 μM in an enzyme assay using rat liver microsomes[1]. Enniatins B decreases the activation of ERK (p44/p42)[2].

  • CAS Number: 917-13-5
  • MF: C33H57N3O9
  • MW: 639.820
  • Catalog: ERK
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 827.0±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 454.0±34.3 °C

Asperulosidic acid

Asperulosidic Acid (ASPA), a bioactive iridoid glycoside, is extracted from the herbs of Hedyotis diffusa Willd. Asperulosidic Acid (ASPA) has anti-tumor, anti-oxidant, and anti-inflammatory activities[1].ASPA is related to the inhibition of inflammatory cytokines (TNF-α, IL-6) and mediators via suppression of the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways[2].

  • CAS Number: 25368-11-0
  • MF: C18H24O12
  • MW: 432.37600
  • Catalog: ERK
  • Density: 1.64±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CG-200745

CG-200745 is a potent HDAC inhibitor, with IC50s of <3 μM for sensitive non-small cell lung cancer (NSCLC) cell lines. CG-200745 induces the accumulation of p53, promotes p53-dependent transactivation, and enhances the expression of proteins encoded by p53 target genes, MDM2 and p21 (Waf1/Cip1) in human prostate cancer cells[1]. CG-200745 attenuates phosphorylation of p38 MAPK in kidneys and it has a renoprotective effect by suppressing renal fibrosis and inflammation in a unilateral ureteral obstruction (UUO) mouse model[2].

  • CAS Number: 936221-33-9
  • MF: C24H33N3O4
  • MW: 427.53700
  • Catalog: MDM-2/p53
  • Density: 1.148±0.06 g/cm3 (20 °C, 760 mmHg)
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

B-Raf IN 2

B-Raf IN 2 is a potent and selective BRAF inhibitor extracted from patent WO2021116055A1, compound Ia. B-Raf IN 2 can be used for the research of cancer[1].

  • CAS Number: 2649372-20-1
  • MF: C20H17F2N5O4S
  • MW: 461.44
  • Catalog: Raf
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Org 48762-0

Org 48762-0 is a potent, orally active and selective p38 inhibitor with EC50 of 0.1 μM. Org 48762-0 reduces LPS-induced TNFα release and prevents bone damage in collagen-induced arthritis in mice[1].

  • CAS Number: 755753-89-0
  • MF: C24H16F2N4
  • MW: 398.41
  • Catalog: p38 MAPK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 520.1±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 268.3±30.1 °C

LY 3009120

LY3009120 is a pan RAF inhibitor which inhibits BRAFV600E, BRAFWT and CRAFWT with IC50s of 5.8, 9.1 and 15 nM, respectively.

  • CAS Number: 1454682-72-4
  • MF: C23H29FN6O
  • MW: 424.514
  • Catalog: Autophagy
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A