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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PT-262

PT-262 is a potent ROCK inhibitor with an IC50 value of around 5 μM. PT-262 induces the loss of mitochondrial membrane potential and elevates the caspase-3 activation and apoptosis. PT-262 inhibits the ERK and CDC2 phosphorylation via a p53-independent pathway. PT-262 blocks cytoskeleton function and cell migration. PT-262 has anti-cancer activity[1][2].

  • CAS Number: 86811-36-1
  • MF: C14H13ClN2O2
  • MW: 276.72
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rineterkib

ERK-IN-1 (compound B) is a RAF and ERK1/2 inhibitor in the treatment of a proliferative disease characterized by activating mutations in the MAPK pathway. The activity is particularly related to the treatment of KRAS-mutant NSCLC (non-small celllung cancer), BRAF-mutant NSCLC, KRAS-mutant pancreatic cancer, KRAS-mutant colorectal cancer (CRC) and KRAS-mutant ovanan cancer[1].

  • CAS Number: 1715025-32-3
  • MF: C26H27BrF3N5O2
  • MW: 578.42
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HPK1-IN-32

HPK1-IN-32 is a potent and selective HPK1 inhibitor with an IC50 of 65 nM. HPK1-IN-32 can be used for the research of HPK1 related disorders or diseases[1].

  • CAS Number: 2766481-17-6
  • MF: C28H37FN8O2
  • MW: 536.64
  • Catalog: MAP4K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LJI308

LJI308 is a new and potent pan-RSK inhibitor, with IC50 of 6 nM, 4 nM, and 13 nM for RSK1, RSK2, and RSK3, respectively.IC50 value: 6/4/13 nMTarget: RSK1/2/3in vitro: LJI308 efficiently inhibits RSK activity. LJI308 inhibites S6K1 with an IC50 of 0.8 μM, representing a 200-fold lower inhibition than that of RSK2. LJI308 inhibits MEK4 less than 50% at 10 μMand HIP kinase 1 less than 50% at 1 μM. [1] LJI308 inhibits the growth and survival of TNBC. LJI308 also suppresses the growth of HTRY-LT cells in 3-dimensional soft agar cultures. LJI308 is one of the first potent and effective targeted therapies for TNBC that, unlike currently utilized drugs, exhibits efficacy in eliminating the CSC population. [2]

  • CAS Number: 1627709-94-7
  • MF: C21H18F2N2O2
  • MW: 368.377
  • Catalog: Ribosomal S6 Kinase (RSK)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 486.6±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 248.1±28.7 °C

Iroxanadine sulfate

Iroxanadine sulfate is a MAPK p38 inhibitor potentially for the treatment of atherosclerosis.

  • CAS Number: 276690-61-0
  • MF: C14H22N4O5S
  • MW: 358.41
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Acumapimod

Acumapimod (BCT197) is an orally active p38 MAP kinase inhibitor, with an IC50 of less than 1 μM for p38α.

  • CAS Number: 836683-15-9
  • MF: C22H19N5O2
  • MW: 385.419
  • Catalog: p38 MAPK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 675.6±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 362.4±31.5 °C

S-99

ASK1-IN-5 (S-99) is an inhibitor of apoptosis signal-regulated kinase 1 (ASK1) and is useful in the study of autoimmune and neurodegenerative diseases[1].

  • CAS Number: 1124381-69-6
  • MF: C16H15F3N6O
  • MW: 364.33
  • Catalog: Apoptosis
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HPK1-IN-9

HPK1-IN-9 is potent inhibitor of HPK1. HPK1 is a serine/threonine protein kinase cloned from hematopoietic progenitor cells and belongs to the MAP4K family of mammalian Ste-20-related protein kinases. HPK1-IN-9 has the potential for the research of HPK1 related diseases (extracted from patent WO2021213317A1, compound 112) [1].

  • CAS Number: 2734168-78-4
  • MF: C30H33N7O2
  • MW: 523.63
  • Catalog: MAP4K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RGB-286638

RGB-286638 is a CDK inhibitor that inhibits the kinase activity of cyclin T1-CDK9, cyclin B1-CDK1, cyclin E-CDK2, cyclin D1-CDK4, cyclin E-CDK3, and p35-CDK5 with IC50s of 1, 2, 3, 4, 5 and 5 nM, respectively; also inhibits GSK-3β, TAK1, Jak2 and MEK1, with IC50s of 3, 5, 50, and 54 nM.

  • CAS Number: 784210-88-4
  • MF: C29H35N7O4
  • MW: 545.633
  • Catalog: MEK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

POP-3MB

POP-3MB (compound 1b) is an ICMT inhibitor (IC50: 2.5 μM). POP-3MB changes the subcellular localization of K-Ras and inhibits Ras activation. POP-3MB also inhibits Erk phosphorylation[1].

  • CAS Number: 1144114-27-1
  • MF: C38H39NO4S
  • MW: 605.79
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC MEK1 Degrader-1

PROTAC MEK1 Degrader-1 is a PROTAC targeting MEK1 with a pIC50 value of 7.0. PROTAC MEK1 Degrader-1 consists of a MEK1 inhibitor and a von Hippel-Lindau ligand. PROTAC MEK1 Degrader-1 can inhibit ERK1/2 phosphorylation. PROTAC MEK1 Degrader-1 shows an antiproliferative activity against A375 cells[1].

  • CAS Number: 2671004-41-2
  • MF: C53H66FIN8O11S2
  • MW: 1201.17
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cannabisin D

Cannabisin D inhibits proliferation and migration of glioblastoma cells through MAPKs signaling[1].

  • CAS Number: 144506-19-4
  • MF: C36H36N2O8
  • MW: 624.68
  • Catalog: p38 MAPK
  • Density: 1.334±0.06 g/cm3
  • Boiling Point: 965.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 537.9±34.3 °C

GNE-8505

GNE-8505 is an orally available inhibitor of Dual leucine zipper kinase (DLK)[1].

  • CAS Number: 1620573-48-9
  • MF: C21H24F3N5O
  • MW: 419.44
  • Catalog: MAP3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cobimetinib

Cobimetinib (GDC-0973, RG7420) is a potent, selective and oral MEK inhibitor with an IC50 of 4.2 nM for MEK1.

  • CAS Number: 934660-93-2
  • MF: C21H21F3IN3O2
  • MW: 531.310
  • Catalog: MEK
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 565.9±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 296.1±30.1 °C

AT-533

AT-533 is a potent Hsp90 and HSV inhibitor. AT-533 suppresses tumor growth and angiogenesis by blocking the HIF-1α/VEGF/VEGFR-2 signaling pathway. AT-533 also inhibits the activation of the downstream pathways, including Akt/mTOR/p70S6K, Erk1/2 and FAK. AT-533 inhibits the tube formation, cell migration, and invasion of human umbilical vein endothelial cells (HUVECs)[1][2][3].

  • CAS Number: 908112-37-8
  • MF: C23H30N4O3
  • MW: 410.51
  • Catalog: HSV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TC-S 7006

Tpl2 Kinase Inhibitor 1 (Compound 1) is a potent and selective Tpl2 (COT kinase, MAP3K8) inhibitor, plays an important role in the regulation of the inflammatory response and the progression of some cancers[1].

  • CAS Number: 871307-18-5
  • MF: C21H14ClFN6
  • MW: 404.82700
  • Catalog: MAP3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ISIS 5132

ISIS 5132 is a 20-base phosphorothioate oligonucleotide that specifically down-regulates c-raf expression.

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

HPK1-IN-18

HPK1-IN-18 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-18 is useful in researching, preventing or ameliorating diseases or disorders associated with HPK1 activity such as cancer (extracted from patent WO2019238067A1, compound 1)[1].

  • CAS Number: 2403598-42-3
  • MF: C24H24N4
  • MW: 368.47
  • Catalog: MAP4K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ERK1/2 inhibitor 8

ERK1/2 inhibitor 8 is a potent ERK inhibitor with an IC50 of 0.48 nM for ERK2 (WO2021110168A1, WX007)[1].

  • CAS Number: 2648368-43-6
  • MF: C23H20ClN7O2S
  • MW: 493.97
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aspirin

Aspirin is a non-selective and irreversible inhibitor of COX-1 and COX-2 with IC50s of 5 and 210 μg/mL.

  • CAS Number: 50-78-2
  • MF: C9H8O4
  • MW: 180.157
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 321.4±25.0 °C at 760 mmHg
  • Melting Point: 134-136 °C(lit.)
  • Flash Point: 131.2±16.7 °C

Sorafenib

Sorafenib (Bay 43-9006) is a potent multikinase inhibitor with IC50s of 6 nM, 20 nM, and 22 nM for Raf-1, B-Raf, and VEGFR-3, respectively.

  • CAS Number: 284461-73-0
  • MF: C21H16ClF3N4O3
  • MW: 464.825
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 523.3±50.0 °C at 760 mmHg
  • Melting Point: 202-204°C
  • Flash Point: 270.3±30.1 °C

Pluripotin

Pluripotin is a dual inhibitor of ERK1 and RasGAP with KDs of 98 nM and 212 nM, respectively. Pluripotin also inhibits RSK1, RSK2, RSK3, and RSK4 with IC50s of 0.5, 2.5, 3.3, and 10.0 µM, respectively.

  • CAS Number: 839707-37-8
  • MF: C27H25F3N8O2
  • MW: 550.535
  • Catalog: ERK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cafestol

Cafestol, one of the major components of coffee, is a coffee-specific diterpene from. Cafestol is a ERK inhibitor for AP-1-targeted activity against PGE2 production and the mRNA expression of cyclooxygenase (COX)-2 in LPS-activated RAW264.7 cells. Cafestol has strong inhibitory activity on PGE2 production by suppressing the NF-kB activation pathway. Cafestol contributes to its beneficial effects through various biological activities such as chemopreventive, antitumorigenic, hepatoprotective, antioxidative and antiinflammatory effects[1].

  • CAS Number: 469-83-0
  • MF: C20H28O3
  • MW: 316.435
  • Catalog: COX
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 468.6±45.0 °C at 760 mmHg
  • Melting Point: 160-162ºC (with decomposition) (ethyl ether pentane )
  • Flash Point: 237.2±28.7 °C

EMODICACID

Emodic acid (NSC624610) is an anthraquinone compound isolated from A. microcarpus, which can inhibit the proliferation of cancer cells by inhibiting the activity of NF-κB. Emodic acid can also inhibit the phosphorylation of p38, ERK and JNK, the secretion of tumor-promoting cytokines IL-1β and IL-6, and the expression of VEGF and MMP, thereby inhibiting the invasion and migration potential of cancer cells[1].

  • CAS Number: 478-45-5
  • MF: C15H8O7
  • MW: 300.22000
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Epieriocalyxin A

epi-Eriocalyxin A (Epieriocalyxin A), a diterpenoid isolated from Isodon eriocalyx, induces colon cancer apoptosis. epi-Eriocalyxin A also inhibits ERK1/2 and JNK activation, which suppresses Bcl-2 expression[1].

  • CAS Number: 191545-24-1
  • MF: C20H24O5
  • MW: 344.402
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 563.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 248.4±30.2 °C

p38-α MAPK-IN-1

p38-α MAPK-IN-1 is an inhibitor of MAPK14 (p38-α), with IC50 of 2300 nM in EFC displacement assay, and 5500 nM in HTRF assay.

  • CAS Number: 443913-15-3
  • MF: C27H35N5O3
  • MW: 477.6
  • Catalog: p38 MAPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Isovitexin

Isovitexin is a flavonoid isolated from rice hulls of Oryza sativa, possesses anti-inflammatory and anti-oxidant activities; Isovitexin acts like a JNK1/2 inhibitor and inhibits the activation of NF-κB.

  • CAS Number: 38953-85-4
  • MF: C21H20O10
  • MW: 432.378
  • Catalog: JNK
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 807.0±65.0 °C at 760 mmHg
  • Melting Point: 220 - 221 °C
  • Flash Point: 287.1±27.8 °C

BIX02189

BIX02189 is a potent and selective MEK5 inhibitor with an IC50 of 1.5 nM. BIX02189 also inhibits ERK5 catalytic activity with an IC50 of 59 nM.

  • CAS Number: 1265916-41-3
  • MF: C27H28N4O2
  • MW: 440.537
  • Catalog: MEK
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 653.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 349.0±31.5 °C

CMK

CMK is a RSK2 kinase inhibitor which exhibits similar potency but less chemical stability compared with FMK.

  • CAS Number: 821794-90-5
  • MF: C18H19ClN4O2
  • MW: 358.822
  • Catalog: Ribosomal S6 Kinase (RSK)
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 647.5±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 345.4±31.5 °C

Sorafenib Tosylate

Sorafenib tosylate is a potent multikinase inhibitor, with IC50s of 6 nM, 20 nM, and 22 nM for Raf-1, B-Raf, and VEGFR-3, respectively.

  • CAS Number: 475207-59-1
  • MF: C28H24ClF3N4O6S
  • MW: 637.027
  • Catalog: Autophagy
  • Density: 1.454 g/cm3
  • Boiling Point: 523.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 270.3ºC