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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(Rac)-Hesperetin-13C,d3

(Rac)-Hesperetin-13C,d3 is the 13C- and deuterium labeled. (Rac)-Hesperetin is the racemate of Hesperetin. Hesperetin is a natural flavanone, and acts as a potent and broad-spectrum inhibitor against human UGT activity. Hesperetin induces apoptosis via p38 MAPK activation.

  • CAS Number: 2750534-85-9
  • MF: C1513CH11D3O6
  • MW: 306.29
  • Catalog: Apoptosis
  • Density: N/A
  • 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

3-Deoxysappanone B

Deoxysappanone B (3-Deoxysappanone B) is a homoisoflavone compound isolated from Caesalpinia sappan L (Lignum Sappan). Deoxysappanone B has anti-neuroinflammatory and neuroprotective effects and inhibits the production of neuroinflammatory mediators by blocking the IκB kinase (IKK)-NF-κB and p38/ERK MAPK pathways. Deoxysappanone B can be used in disease studies of neuritis and inflammation-related neurological damage[1].

  • CAS Number: 113122-54-6
  • MF: C16H14O5
  • MW: 286.279
  • Catalog: p38 MAPK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 587.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 225.0±23.6 °C

ASK1-IN-3

ASK1-IN-3 is a potent and selective ASK1 kinase inhibitor with IC50 of 33.8 nM, as well as inhibits several cell cycle regulating kinases. ASK1-IN-3 has strong HepG2 cancer cells apoptosis induction and potent cell cycle arrest activities[1].

  • CAS Number: 2426705-19-1
  • MF: C18H18N8O2
  • MW: 378.39
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

12-Hydroxyabieta-8(14),9(11),12-trien-7-one

Sugiol is an abietane diterpenoid, can be isolated from Calocedrus formosana bark. Sugiol has anti-inflammatory activity, could effectively reduce intracellular reactive oxygen species (ROS) production in lipopolysaccharide (LPS)-stimulated macrophages[1].

  • CAS Number: 511-05-7
  • MF: C20H28O2
  • MW: 300.435
  • Catalog: Interleukin Related
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 437.2±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 186.4±21.3 °C

NG25 trihydrochloride

NG25 trihydrochloride is a type II kinase inhibitor that inhibits MAP4K2 and TAK1. It also inhibits the Src family kinases Src and LYN and Abl family kinases as well as CSK, FER, and p38α. NG 25 prevents TNF-α-induced IKKα/β phosphorylation and IκB-α degradation in L929 cells. It inhibits secretion of IFN-α and IFN-β induced by CpG type B and CL097, respectively. NG 25 decreases cell viability of HCT116KRASWT, and to a greater degree of HCT116KRASG13D, colorectal cancer cells in a concentration-dependent manner. It also reduces tumor growth and increases the number of TUNEL-positive tumor cells in a CT26KRASG12D mouse orthotopic model of colorectal cancer.

  • CAS Number: 2108554-00-1
  • MF: C29H33Cl3F3N5O2
  • MW: 646.96
  • Catalog: MAP3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JNK3 inhibitor-4

JNK3 inhibitor-4 is a potent inhibitor of JNK3 (IC50=1.0 nM) based on 2-aryl-1-pyrimidinyl-1H-imidazole-5-yl acetonitrile. JNK3 inhibitor-4 shows excellent selectivity over other protein kinases including isoforms JNK1 (IC50=143.9 nM) and JNK2 (IC50=298.2 nM)[1]. JNK3 inhibitor-4 has neuroprotective effect and predicated blood-brain barrier permeability[1].

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

MPT0B392

MPT0B392, an orally active quinoline derivative, induces c-Jun N-terminal kinase (JNK) activation, leading to apoptosis. MPT0B392 triggers induction of the mitotic arrest, followed by mitochondrial membrane potential loss and caspases cleavage by activation of JNK and ultimately leads to apoptosis[1].

  • CAS Number: 1346169-92-3
  • MF: C19H20N2O6S
  • MW: 404.44
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ZINC12409120

ZINC12409120 is a high selective ERK inhibitor. ZINC12409120 acts on disrupting FGF23:α-Klotho interaction to inhibit ERK activity with an IC50 of 5.0 μM[1].

  • CAS Number: 1010888-06-8
  • MF: C20H16N4O2
  • MW: 344.37
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Carnosol

Carnosol is a potent Ribosomal S6 Kinase (RSK2) inhibitor that could be useful for treating gastric cancer, with an IC50 of ~5.5 μM.

  • CAS Number: 5957-80-2
  • MF: C20H26O4
  • MW: 330.418
  • Catalog: Ribosomal S6 Kinase (RSK)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 524.8±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 187.0±23.6 °C

Guggulsterone E&Z

Guggulsterone is a plant sterol derived from the gum resin of the tree Commiphora wightii. Guggulsterone inhibits the growth of a wide variety of tumor cells and induces apoptosis through down regulation of antiapoptotic gene products (IAP1, xIAP, Bfl-1/A1, Bcl-2, cFLIP and survivin), modulation of cell cycle proteins (cyclin D1 and c-Myc), activation of caspases and JNK, inhibition of Akt[1]. Guggulsterone, a farnesoid X receptor (FXR) antagonist, decreases CDCA-induced FXR activation with IC50s of 17 and 15 μM for Z- and E-Guggulsterone, respectively[2].

  • CAS Number: 95975-55-6
  • MF: C21H28O2
  • MW: 312.446
  • Catalog: Apoptosis
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 463.3±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 172.3±25.7 °C

GNE 220

GNE-220 is a potent and selective inhibitor of MAP4K4 with an IC50 of 7 nM.

  • CAS Number: 1199590-75-4
  • MF: C25H26N8
  • MW: 438.53
  • Catalog: MAP4K
  • Density: N/A
  • 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

TAK-715

TAK-715 is a p38 MAPK inhibitor for p38α with IC50 of 7.1 nM, 28-fold more selective for p38α over p38β, no inhibition to p38γ/δ, JNK1, ERK1, IKKβ, MEKK1 or TAK1.IC50 value: 7.1 nM [1]Target: p38α MAPKin vitro: TAK 715 inhibits LPS-stimulated release of TNF-alpha from THP-1 with IC50 of 48 nM [1]. TAK 715 (10 μM) inhibits Wnt-3a-induced hDvl2 phosphorylation and the hDvl2 shift in U2OS-EFC cells [2]. The amide NH of TAK 715 is hydrogen bonded to the main-chain carbonyl of Met109 of p38 alpha. TAK 715 binds relatively high in the ATP pocket, occupying the hydrophobic back pocket, the adenine region and the front pocket of p38 as well as extending to most of the length of the Gly-rich loop [3].in vivo: TAK 715 (10 mg/kg, po) inhibits LPS-induced TNF-alpha production in mice with 87.6% inhibition. TAK 715 has a modest mouse bioavailability of 18.4% and a slightly improved rat bioavailability of 21.1%. TAK 715 has a modest mouse bioavailability of 18.4% and a slightly improved rat bioavailability of 21.1%. TAK 715 results in Cmax of 0.19 μg/mL and AUC(0-24 hours) of 1.16 μg·h/mL in rats. TAK 715 (30 mg/kg, po) significantly reduces the secondary paw volume with 25 % inhibition in a rat adjuvant-induced arthritis (AA) model [1].

  • CAS Number: 303162-79-0
  • MF: C24H21N3OS
  • MW: 399.508
  • Catalog: p38 MAPK
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 495.3±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 253.3±28.7 °C

PF-03715455

PF-03715455 is a potent inhaled p38 MAPK inhibitor. PF-03715455 shows some selectivity for p38α over p38β with respective IC50 values of 0.88 and 23 nM. PF-03715455 potently inhibits LPS-induced TNFα production in human whole blood (IC50=1.7 nM). PF-03715455 has potential for the treatment of COPD (chronic obstructive pulmonary disease)[1][2].

  • CAS Number: 1056164-52-3
  • MF: C35H34ClN7O3S2
  • MW: 700.27300
  • Catalog: p38 MAPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ERKtide

ERKtide is a biological active peptide. (ERKtide is a peptide substrate for ERK2. Extracellular regulated protein kinase 2 (ERK2) is a eukaryotic protein kinase whose activity is regulated by mitogenic stimuli.)

  • CAS Number: 287721-17-9
  • MF: C58H93N19O16
  • MW: 1312.48
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NF-κB/MAPK-IN-1

NF-κB/MAPK-IN-1 (compound 11a) is a potent inhibitor of NF-κB and MAPK pathway. NF-κB/MAPK-IN-1 shows inhibitory activity against NO production, with an IC50 of 6.96 µM. NF-κB/MAPK-IN-1 suppresses LPS-induced iNOS, COX-2, ERΚ and P38 signaling activation. NF-κB/MAPK-IN-1 can prevent LPS induced inflammatory response in macrophages. NF-κB/MAPK-IN-1 can be used for rheumatoid arthritis (RA) research[1].

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

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

CC-90003

CC-90003 is an irreversible and selective inhibitor of ERK 1/2 with antitumor activity.

  • CAS Number: 1621999-82-3
  • MF: C22H21F3N6O2
  • MW: 458.44
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SM 7368

SM-7368 is a potent NF-kB inhibitor that targets downstream of MAPK p38 activation[1]. SM-7368 inhibits TNF-α-induced MMP-9 upregulation. SM-7368 can be used for the research of chemotherapies targeting TNF-α-mediated tumor invasion and metastasis [2].

  • CAS Number: 380623-76-7
  • MF: C10H5ClN4O5S
  • MW: 328.68900
  • Catalog: p38 MAPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Trametinib-13C,d3

Trametinib-13C,d3 is the 13C- and deuterium labeled. Trametinib (GSK1120212; JTP-74057) is an orally active MEK inhibitor that inhibits MEK1 and MEK2 with IC50s of about 2 nM. Trametinib activates autophagy and induces apoptosis[1][2].

  • CAS Number: 2712126-59-3
  • MF: C2513CH20D3FIN5O4
  • MW: 619.41
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Regorafenib D3

Regorafenib D3 (BAY 73-4506 D3) is a deuterium labeled Regorafenib. Regorafenib is a multi-targeted receptor tyrosine kinase inhibitor[1].

  • CAS Number: 1255386-16-3
  • MF: C21H12D3ClF4N4O3
  • MW: 485.83400
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ERK1/2 inhibitor 5

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: 2560552-75-0
  • MF: C28H32ClFN6O5
  • MW: 587.04
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BMS-751324

BMS-751324 is a novel clinical prodrug of BMS-582949, which is a highly selective p38α MAPK inhibitor with IC50 of 13 nM; BMS-751324 is effectively bioconverted into parent drug BMS-582949 in vivo by alkaline phosphatase and esterase in a stepwise manner; demonstrates similar efficacy in rat LPS-induced TNFα pharmacodynamic model and rat adjuvant arthritis model compared with BMS-582949; BMS-751324 is indeed effective in addressing the pH-dependent absorption issue associated with BMS-582949.

  • CAS Number: 948842-66-8
  • MF: C32H35N6O10P
  • MW: 694.628
  • Catalog: p38 MAPK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TAS0612

TAS0612 is an orally novel inhibitor of RSK、AKT and S6K. TAS0612 has broad-spectrum activity against tumor models via inhibiting cell growth[1].

  • CAS Number: 2148902-58-1
  • MF: C27H34F3N9O2
  • MW: 573.61
  • Catalog: Ribosomal S6 Kinase (RSK)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(Rac)-Hesperetin

(Rac)-Hesperetin is the racemate of Hesperetin. Hesperetin is a natural flavanone, and acts as a potent and broad-spectrum inhibitor against human UGT activity. Hesperetin induces apoptosis via p38 MAPK activation.

  • CAS Number: 69097-99-0
  • MF: C16H14O6
  • MW: 302.27900
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 227 - 232 °C
  • Flash Point: N/A

GNE-495

GNE-495 is a potent and selective MAP4K4 inhibitor with an IC50 of 3.7 nM.

  • CAS Number: 1449277-10-4
  • MF: C22H20FN5O2
  • MW: 405.425
  • Catalog: MAP4K
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 734.5±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 398.0±32.9 °C

EBI-1051

EBI-1051 is a highly potent and orally efficacious MEK inhibitor with an IC50 of 3.9 nM.

  • CAS Number: 1801896-05-8
  • MF: C18H15F2IN2O5
  • MW: 504.22
  • Catalog: MEK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HPK1-IN-26

HPK1-IN-26 is a HPK1 and GLK inhibitor extracted from patent WO2021254118A1 compound 1. HPK1-IN-26 can be used for the research of animal pathogen infection[1].

  • CAS Number: 2229042-24-2
  • MF: C19H21N5OS
  • MW: 367.47
  • Catalog: MAP4K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A