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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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

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

necrosulfonamide

(E/Z)-Necrosulfonamide is a racemic compound of Necrosulfonamide (HY-100573). Necrosulfonamide is a necroptosis inhibitor acting by selectively targeting the mixed lineage kinase domain-like protein (MLKL). Necrosulfonamide prevents MLKL-RIP1-RIP3 necrosome complex from interacting with its downstream effectors. MLKL is a critical substrate of RIP3 during the induction of necrosis[1][2].

  • CAS Number: 432531-71-0
  • MF: C18H15N5O6S2
  • MW: 461.472
  • Catalog: Mixed Lineage Kinase
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

URMC-099

URMC-099 is an orally bioavailable and potent mixed lineage kinase type 3 (MLK3) (IC50=14 nM) inhibitor with with excellent blood-brain barrier penetration properties.

  • CAS Number: 1229582-33-5
  • MF: C27H27N5
  • MW: 421.537
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cornuside

Cornuside is a secoiridoid glucoside isolated from the fruit of Cornus officinalis Sieb. et Zucc., which is a traditional oriental medicine for treating inflammatory diseases and invigorating blood circulation. Cornuside inhibits mast cell-mediated allergic response by down-regulating MAPK and NF-κB signaling pathways. Cornuside has anti-allergic effects in vivo and in vitro which suggests a therapeutic application of this agent in inflammatory allergic diseases[1].

  • CAS Number: 131189-57-6
  • MF: C24H30O14
  • MW: 542.487
  • Catalog: p38 MAPK
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 817.6±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 274.5±27.8 °C

SB 202190 hydrochloride

SB 202190 hydrochloride is a selective p38 MAP kinase inhibitor with IC50s of 50 nM and 100 nM for p38α and p38β2, respectively. SB 202190 hydrochloride binds to the ATP pocket of the active recombinant human p38 kinase with a Kd of 38 nM. SB 202190 hydrochloride has anti-cancer activity[1][2]. SB202190 hydrochloride induces autophagy[3].

  • CAS Number: 350228-36-3
  • MF: C20H15ClFN3O
  • MW: 367.80
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GW5074

GW 5074 is a potent and selective c-Raf inhibitor with IC50 of 9 nM, and has no effect on the activities of JNK1/2/3, MEK1, MKK6/7, CDK1/2, c-Src, p38 MAP, VEGFR2 or c-Fms.

  • CAS Number: 220904-83-6
  • MF: C15H8Br2INO2
  • MW: 520.942
  • Catalog: Raf
  • Density: 2.2±0.1 g/cm3
  • Boiling Point: 561.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 293.3±30.1 °C

ASK1-IN-4

ASK1-IN-4 (Compound 17) is an ASK1 inhibitor (IC50=0.2 μM). ASK1-IN-4 interacts with ATP-binding site of ASK1[1].

  • CAS Number: 1427538-26-8
  • MF: C18H14BrNO4S2
  • MW: 452.34
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Gardenin A

Gardenin A is an orally active and synthetic PMF analogue with the neurotrophic effect for neurite outgrowth and neuronal differentiation. Gardenin A promotes neuritogenesis via activating MAPK/ERK, PKC, and PKA, but not TrkA, CREB signaling pathways. Gardenin A also has sedative, anxiolytic, antidepressant, and anticonvulsant effects[1][2].

  • CAS Number: 21187-73-5
  • MF: C21H22O9
  • MW: 418.39400
  • Catalog: PAK
  • Density: 1.3g/cm3
  • Boiling Point: 624.2ºC at 760 mmHg
  • Melting Point: 162-163ºC
  • Flash Point: 218.5ºC

Baicalein-5,6,7-trimethylether

5,6,7-Trimethoxyflavone is a novel p38-α MAPK inhibitor with an anti-inflammatory effect. 5,6,7-Trimethoxyflavone is isolated from several plants including Zeyhera tuberculosa, Callicarpa japonica, and Kickxia lanigera[1].

  • CAS Number: 973-67-1
  • MF: C18H16O5
  • MW: 312.31700
  • Catalog: p38 MAPK
  • Density: 1.242g/cm3
  • Boiling Point: 497.4ºC at 760 mmHg
  • Melting Point: 165-167°C
  • Flash Point: 221.3ºC

BIX02188

BIX02188 is a potent MEK5-selective inhibitor with an IC50 of 4.3 nM. BIX02188 inhibits ERK5 catalytic activity, with an IC50 of 810 nM.

  • CAS Number: 334949-59-6
  • MF: C25H24N4O2
  • MW: 412.484
  • Catalog: ERK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 615.8±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 326.2±31.5 °C

Z16078526

Z16078526 induces endogenous Ucp1 expression, promotes p38 MAPK phosphorylation and lipolysis in primary mouse brown adipocytes. Z16078526 activates thermogenic gene expression and mitochondrial activity (uncoupled respiration) in mouse brown adipocytes. Z16078526 also stimulates thermogenesis in the mouse[1].

  • CAS Number: 852222-94-7
  • MF: C18H17N3O4S
  • MW: 371.41
  • Catalog: p38 MAPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

U0126-EtOH

U0126 is a potent and non-ATP competitive MEK1 and MEK2 inhibitor, with IC50s of 70 nM and 60 nM, respectively.

  • CAS Number: 1173097-76-1
  • MF: C20H22N6OS2
  • MW: 426.558
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: 612.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 324.2ºC

(-)-Zuonin A

(-)-Zuonin A (D-Epigalbacin), a naturally occurring lignin, is a potent, selective JNKs inhibitor, with IC50s of 1.7 μM, 2.9 μM and 1.74 μM for JNK1, JNK2 and JNK3, respectively[1].

  • CAS Number: 84709-25-1
  • MF: C20H20O5
  • MW: 340.37
  • Catalog: JNK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ravoxertinib

Ravoxertinib (GDC-0994) is an orally bioavailable ERK kinase inhibitor with an IC50 of 6.1 nM and 3.1 nM for ERK1 and ERK2, respectively.

  • CAS Number: 1453848-26-4
  • MF: C21H18ClFN6O2
  • MW: 440.858
  • Catalog: ERK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 734.6±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 398.0±35.7 °C

Vemurafenib-d7

Vemurafenib-d7 is deuterium labeled Vemurafenib. Vemurafenib (PLX4032) is a first-in-class, selective, potent inhibitor of B-RAF kinase, with IC50s of 31 and 48 nM for RAFV600E and c-RAF-1, respectively[1][4]. Vemurafenib induces cell autophagy[5].

  • CAS Number: 1365986-73-7
  • MF: C23H11D7ClF2N3O3S
  • MW: 496.97
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Anticancer agent 164

CML-IN-1 (compound 7) is a potent anticancer agent. CML-IN-1 displays very good induced-apoptosis effect for human chronic myeloid leukemia (CML) cell line K562. CML-IN-1 exerts its effect via a significantly reduced protein phosphorylation of PI3K/Akt signal pathway. CML-IN-1 (compound 4) also inhibits cell proliferation by suppressing the MEK/ERK signaling pathway in colorectal cancer[1][2].

  • CAS Number: 2235393-30-1
  • MF: C21H23F3N8O2S2
  • MW: 540.58
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ERK1/2 inhibitor 7

ERK1/2 inhibitor 7 is a potent ERK inhibitor with an IC50 of 0.94 nM for ERK2 (WO2021110168A1, WX006)[1].

  • CAS Number: 2648455-13-2
  • MF: C23H22FN7OS
  • MW: 463.53
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

B-Raf IN 8

B-Raf IN 8 (compound 7g) is a potent B-Raf inhibitor, with an IC50 of 70.65 nM. B-Raf IN 8 exhibits antitumor activity against hepatocellular carcinoma (HEPG-2), colon carcinoma (HCT-116), mammary gland (MCF-7) and human prostate cancer (PC-3) cells, with IC50 values of 9.78, 13.78, 18.52 and 29.85 µM[1].

  • CAS Number: 1215313-19-1
  • MF: C18H17N3O2
  • MW: 307.35
  • Catalog: Raf
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PD0325901

PD0325901 is a selective and cell permeable MEK inhibitor with an IC50 of 0.33 nM.

  • CAS Number: 391210-10-9
  • MF: C16H14F3IN2O4
  • MW: 482.193
  • Catalog: Autophagy
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 112-114ºC
  • Flash Point: N/A

sertaconazole

Sertaconazole (FI7056 free base) is a broad-spectrum topical antifungal agent, exhibits anti-inflammatory activity via activation of a p38-COX-2-PGE2 pathway. Sertaconazole is also a microtubule inhibitor, shows antiproliferative effect, induces apoptosis and autophagy, and can also inhibit the migration of cells[1][2][3][4].

  • CAS Number: 99592-32-2
  • MF: C20H15Cl3N2OS
  • MW: 437.770
  • Catalog: Fungal
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 614.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 325.2±31.5 °C

Cyclocurcumin

Cyclocurcumin is a potent p38α inhibitor. Cyclocurcumin shows antirheumatic, antivasoconstrictive and antioxidant activities[1][2][3].

  • CAS Number: 153127-42-5
  • MF: C21H20O6
  • MW: 368.38
  • Catalog: p38 MAPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MY-673

MY-673 is a colchicine binding site inhibitor (CBSI), that inhibits tubulin polymerization. MY-673 inhibits the ERK signaling pathway, which in turn affects SMAD4 protein expression levels in the TGF-β/SMAD pathway. MY-673 inhibited cell proliferation, migration and induced apoptosis in vivo and in vitro[1].

  • CAS Number: 2944459-96-3
  • MF: C18H14N2O4
  • MW: 322.31
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rutin hydrate

Rutin hydrate is a flavonol glycoside, able to cross the blood-brain barrier, and acts by inhibiting JNK and ERK1/2 activation and activating mTOR signalling.

  • CAS Number: 207671-50-9
  • MF: C27H3O16.xH2O
  • MW: 664.56300
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 195°C dec. (Lit.)
  • Flash Point: N/A

IACS-52825

IACS-52825 is a potent and selective DLK inhibitor with Kd of 1.3 nM, useful for the study of chemotherapy-induced peripheral neuropathy[1].

  • CAS Number: 2640376-72-1
  • MF: C16H13F7N4O2
  • MW: 426.29
  • Catalog: MAP3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SJFα

SJFα is a 13-atom linker PROTAC. SJFα degrades p38α with a DC50 of 7.16  nM, but is far less effective at degrading p38δ (DC50=299 nM) and does not degrade the other p38 isoforms (β and γ) at concentrations up to 2.5 µM[1].

  • CAS Number: 2254609-27-1
  • MF: C59H67F2N7O11S
  • MW: 1120.27
  • Catalog: p38 MAPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

p38 MAP Kinase Inhibitor III

p38 MAP Kinase Inhibitor III (compound 7h) is a p38 MAPK inhibitor with an 50 of 0.9 μM. p38 MAP Kinase Inhibitor III also inhibits IL-1β and TNF-α release with 50 values of 0.37 μM and 0.044 μM, respectively[1].

  • CAS Number: 581098-48-8
  • MF: C23H21FN4S
  • MW: 404.503
  • Catalog: p38 MAPK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 589.4±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 310.2±32.9 °C

2,5-Dihydroxyacetophenone

2,5-Dihydroxyacetophenone, isolated from Rehmanniae Radix Preparata, inhibits the production of inflammatory mediators in activated macrophages by blocking the ERK1/2 and NF-κB signaling pathways[1].

  • CAS Number: 490-78-8
  • MF: C8H8O3
  • MW: 152.147
  • Catalog: ERK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 329.2±27.0 °C at 760 mmHg
  • Melting Point: 204-206 °C(lit.)
  • Flash Point: 167.1±20.2 °C