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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Longdaysin

Longdaysin is a CK1α, CK1δ, and extracellular signal-regulated kinase 2 (ERK2) inhibitor with IC50s of  5.6 µM, 8.8 µM, and 52 µM, respectively[1][2].

  • CAS Number: 1353867-91-0
  • MF: C16H16F3N5
  • MW: 335.33
  • Catalog: Casein Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HPK1-IN-29

HPK1-IN-29 is a potent inhibitor of HPK1. Hematopoietic progenitor kinase 1 (HPK1) is a negative regulator of the activation response of dendritic cells (DCs), T cells and B cells. HPK1-IN-29 enhances the body's anti-tumor immunity. HPK1-IN-29 has the potential for the research of immune-related diseases, especially tumor (extracted from patent WO2021175270A1, compound 38)[1].

  • CAS Number: 2699604-50-5
  • MF: C26H18F3N5O2
  • MW: 489.45
  • Catalog: MAP4K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RAF709

RAF709 is a potent, selective, and efficacious RAF inhibitor with IC50s of 0.4 nM and 0.5 nM for BRAF and CRAF, respectively[1]. Antitumor efficacy[1].

  • CAS Number: 1628838-42-5
  • MF: C28H29F3N4O4
  • MW: 542.559
  • Catalog: Raf
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

trans-Zeatin-d5

trans-Zeatin-d5 is deuterium labeled trans-Zeatin. trans-Zeatin is a plant cytokinin, which plays an important role in cell growth, differentiation, and division; trans-Zeatin also inhibits UV-induced MEK/ERK activation.

  • CAS Number: 72963-19-0
  • MF: C10H8D5N5O
  • MW: 224.27
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AL 8697

AL 8697 is a selective p38 MAPK inhibitor with IC50s of 6 nM and 82 nM for p38α and p38β, respectively[1].

  • CAS Number: 1057394-06-5
  • MF: C21H21F3N4O
  • MW: 402.41
  • Catalog: p38 MAPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ERK Inhibitor

ERK-IN-4 is an ERK inhibitor binds preferentially to ERK2 with a Kd of 5 μM. ERK-IN-4 specificity inhibits ERK Rsk-1 and Elk-1 phosphorylation. ERK-IN-4 has little effect on ERK protein phosphorylation by its upstream activator MEK1/2[1].

  • CAS Number: 1049738-54-6
  • MF: C14H17ClN2O3S
  • MW: 328.814
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DB1113

DB1113 (Example 24) is a bifunctional compound targeted protein degradation of kinases. DB1113 degrades ABL1, ABL2, BLK, CDK11B, CDK4, CSK, EPHA3, FER, GAK, LIMK1, MAP3K20, MAP4K1, MAP4K2, MAP4K3, MAP4K5, MAPK14, MAPK7, MAPK8, MAPK9, MAPKAPK2, MAPKAPK3, NLK, PDIK1L, PTK2B, RIPK1, RPS6KA1, RPS6KA3, SIK2, SIK3, STK35, TNK2, and ULK1. DB1113 can be used for research of disease or disorder mediated by aberrant kinase activity[1].

  • CAS Number: 2769753-53-7
  • MF: C59H68F3N13O6S
  • MW: 1144.31
  • Catalog: Ferroptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SCH772984

SCH772984 potently inhibits ERK1 and ERK2 activity with IC50s of 4 and 1 nM, respectively.

  • CAS Number: 942183-80-4
  • MF: C33H33N9O2
  • MW: 587.674
  • Catalog: ERK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 857.3±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 472.3±34.3 °C

LXH254

LXH254 is a potent CRAF inhibitor extracted from patent WO2018051306A1, Compound A. LXH254 also is a potent BRAF inhibitor.

  • CAS Number: 1800398-38-2
  • MF: C25H25F3N4O4
  • MW: 502.49
  • Catalog: Raf
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pyrazolanthrone (SP600125)

SP600125 is a reversible and ATP-competitive JNK inhibitor with IC50s of 40, 40 and 90 nM for JNK1, JNK2 and JNK3, respectively.

  • CAS Number: 129-56-6
  • MF: C14H8N2O
  • MW: 220.226
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 489.3±14.0 °C at 760 mmHg
  • Melting Point: 281~282℃
  • Flash Point: 246.8±26.5 °C

ERK1/2 inhibitor 6

ERK1/2 inhibitor 6 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 6 has the potential for the research or prevention of cancer, inflammation or other proliferative diseases (extracted from patent WO2021063335A1, compound 1)[1].

  • CAS Number: 2634816-13-8
  • MF: C27H29ClFN7O5
  • MW: 586.01
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MK2-IN-1

MK2-IN-1 is a potent and selecitve MAPKAPK2(MK2) inhibitor(IC50=0.11 uM) with a non-ATP competitive binding mode.IC50 value: 0.11 uM [1]Target: MAPKAPK2(MK2) inhibitorMK2-IN-1 was profiled for kinase selectivity by screening against a broad panel of 150 protein kinases at a concentration of 10 μM, and only CK1γ3 was significantly inhibited at greater than 50%. MK2-IN-1 inhibited pro-inflammatory cytokine secretion from the human THP1 acute monocytic leukemia cell line, causing dose-dependent inhibition of LPS-stimulated TNFα and IL6 secretion. MK2-IN-1 also dose dependently inhibited IL1β-stimulated matrixmetalloprotease (MMP)13 secretion from the SW1353 chondrosarcoma cell line and human primary chondrocyte cultures. Of note, given its high degree of selectivity, our data suggest that MK2-IN-1 may be an excellent pharmacologic tool for specifically exploring and validating MK2 biology [3].

  • CAS Number: 1314118-92-7
  • MF: C27H25ClN4O2
  • MW: 472.966
  • Catalog: MAPKAPK2 (MK2)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 699.2±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 376.7±31.5 °C

Butyzamide

Butyzamide is an orally active activator of Mpl, a thrombopoietin (TPO) receptor. Butyzamide increases the phosphorylation level of JAK2, STAT3, STAT5 and MAPK. Butyzamide increases the level of human platelets in mouse xenotransplantation assay[1].

  • CAS Number: 1110767-45-7
  • MF: C29H32Cl2N2O5S
  • MW: 591.55
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BI 78D3

BI-78D3 functions as a substrate competitive inhibitor of JNK, inhibit the JNK kinase activity (IC50=280 nM).

  • CAS Number: 883065-90-5
  • MF: C13H9N5O5S2
  • MW: 379.37100
  • Catalog: JNK
  • Density: 1.922g/cm3
  • Boiling Point: 705.721ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 380.606ºC

Semapimod

Semapimod, an inhibitor of proinflammatory cytokine production, can inhibit TNF-α, IL-1β, and IL-6. Semapimod inhibits TLR4 signaling (IC50≈0.3 μM). Semapimod inhibits p38 MAPK and nitric oxide production in macrophages. Semapimod has potential in a variety of inflammatory and autoimmune disorders[1][2][3].

  • CAS Number: 352513-83-8
  • MF: C34H52N18O2
  • MW: 744.90
  • Catalog: Interleukin Related
  • Density: 1.39
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Debromohymenialdisine

Debromohymenialdisine (10Z-Debromohymenialdisine) is a pyrrole alkaloid. Debromohymenialdisine has moderate inhibitory activity with an IC50 value of 881 nM in the initial Raf/MEK-1/MAPK signaling cascade assay. Debromohymenialdisine can be used for the research of proliferation and differentiation[1].

  • CAS Number: 75593-17-8
  • MF: C11H11N5O2
  • MW: 245.237
  • Catalog: MEK
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: >250ºC (dec.)
  • Flash Point: N/A

PLX8394

PLX8394 is a potent and selective Raf inhibitor, with an IC50 of appr 5 nM for BRAFV600E.

  • CAS Number: 1393466-87-9
  • MF: C25H21F3N6O3S
  • MW: 542.533
  • Catalog: Raf
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 786.8±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 429.6±35.7 °C

PLK1/p38γ-IN-1

PLK1/p38γ-IN-1(compound 14) is a multitarget inhibitors ofPLK1andp38γ. PLK1/p38γ-IN-1inhibits the growth of human hepatocellular carcinoma and hepatoblastoma cells in vitro[1].

  • CAS Number: 2418614-81-8
  • MF: C21H26ClN3O2
  • MW: 387.90
  • Catalog: Polo-like Kinase (PLK)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Honokiol

Honokiol is a bioactive, biphenolic phytochemical that possesses potent antioxidative, anti-inflammatory, antiangiogenic, and anticancer activities by targeting a variety of signaling molecules. It inhibits the activation of Akt and enhances the phosphorylation of ERK1/ERK2.

  • CAS Number: 35354-74-6
  • MF: C18H18O2
  • MW: 266.334
  • Catalog: Autophagy
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 400.1±40.0 °C at 760 mmHg
  • Melting Point: 87.5ºC
  • Flash Point: 184.0±21.9 °C

Tauroursodeoxycholic Acid-d4 MaxSpec® Standard

Tauroursodeoxycholate-d4 is deuterium labeled Tauroursodeoxycholate. Tauroursodeoxycholate (Tauroursodeoxycholic acid) is an endoplasmic reticulum (ER) stress inhibitor. Tauroursodeoxycholate significantly reduces expression of apoptosis molecules, such as caspase-3 and caspase-12. Tauroursodeoxycholate also inhibits ERK.

  • CAS Number: 2410279-94-4
  • MF: C26H41D4NO6S
  • MW: 503.73
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CGP 57380

CGP 57380 is a cell-permeable pyrazolo-pyrimidine compound that acts as a selective inhibitor of Mnk1 with IC50 of 2.2 μM, but has no inhibitory activity against p38, JNK1, ERK1/2, PKC, or Src-like kinases.

  • CAS Number: 522629-08-9
  • MF: C11H9FN6
  • MW: 244.228
  • Catalog: MNK
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 541.6±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 281.4±30.1 °C

D-JNKI-1

D-JNKI-1 is a specific inhibitor of JNK, and strongly interferes with JNK activation.

  • CAS Number: 1445179-97-4
  • MF: C164H286N66O40
  • MW:
  • Catalog: Peptides
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CC-99677

CC-99677 is a potent, covalent, and irreversible inhibitor of the mitogen-activated protein (MAP) kinase-activated protein kinase-2 (MK2) pathway in both biochemical (IC50=156.3 nM) and cell based assays (EC50=89 nM). CC-99677 is extracted from patent WO2020236636, compound 1[1].

  • CAS Number: 1887069-10-4
  • MF: C22H20ClN5O3S
  • MW: 469.94
  • Catalog: MAPKAPK2 (MK2)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MK2-IN-1 (hydrochloride)

MK2-IN-1 hydrochloride is a potent and selecitve MAPKAPK2(MK2) inhibitor(IC50=0.11 uM) with a non-ATP competitive binding mode.IC50 value: 0.11 uM [1]Target: MAPKAPK2(MK2) inhibitorMK2-IN-1 was profiled for kinase selectivity by screening against a broad panel of 150 protein kinases at a concentration of 10 μM, and only CK1γ3 was significantly inhibited at greater than 50%. MK2-IN-1 inhibited pro-inflammatory cytokine secretion from the human THP1 acute monocytic leukemia cell line, causing dose-dependent inhibition of LPS-stimulated TNFα and IL6 secretion. MK2-IN-1 also dose dependently inhibited IL1β-stimulated matrixmetalloprotease (MMP)13 secretion from the SW1353 chondrosarcoma cell line and human primary chondrocyte cultures. Of note, given its high degree of selectivity, our data suggest that MK2-IN-1 may be an excellent pharmacologic tool for specifically exploring and validating MK2 biology [3].

  • CAS Number: 1314118-94-9
  • MF: C27H26Cl2N4O2
  • MW: 509.427
  • Catalog: MAPKAPK2 (MK2)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HPK1-IN-13

HPK1-IN-13 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-13 has the potential for the research of HPK1 related diseases (extracted from patent WO2021213317A1, compound 64) [1].

  • CAS Number: 2734168-30-8
  • MF: C25H24FN5O2
  • MW: 445.49
  • Catalog: MAP4K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MLKL-IN-2

MLKL-IN-2 is a MLKL inhibitor extracted from patent WO2021224505A1, compound (i)[1].

  • CAS Number: 899759-16-1
  • MF: C26H25N5O
  • MW: 423.51
  • Catalog: Mixed Lineage Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HPK1-IN-15

HPK1-IN-15 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-15 is useful in researching, preventing or ameliorating diseases or disorders associated with HPK1 activity such as cancer (extracted from patent WO2018049200A1, compound 50)[1].

  • CAS Number: 2201098-03-3
  • MF: C24H21ClF3N5
  • MW: 471.91
  • Catalog: MAP4K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Osmundacetone

(E)-Osmundacetone is the isomer of Osmundacetone. Osmundacetone significantly suppresses the phosphorylation of MAPKs, including JNK, ERK, and p38 kinases. Osmundacetone has a neuroprotective effect against oxidative stress[1].

  • CAS Number: 123694-03-1
  • MF: C10H10O3
  • MW: 178.18500
  • Catalog: ERK
  • Density: 1.264g/cm3
  • Boiling Point: 382.5ºC at 760mmHg
  • Melting Point: 173-175ºC
  • Flash Point: 199.3ºC

Tat-NR2B9c TFA

Tat-NR2B9c (TFA) is a 20-aa peptide, which acts as a postsynaptic density-95 (PSD-95) inhibitor, with an EC50 of 6.7 nM for PSD-95d2 (PSD-95 PDZ domain 2), and 670 nM for PSD-95d1[1]. Tat-NR2B9c also reduces NMDA-induced p38 activation, and possesses neuroprotective efficacy[2].

  • CAS Number: 1834571-04-8
  • MF: C107H189F3N42O32
  • MW: 2632.90
  • Catalog: p38 MAPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CCT241161

CCT241161 is an orally active pan-RAF inhibitor with IC50s of 3, 6, 10, 15 and 30 nM for LCK, CRAF, SRC, V600E-BRAF and BRAF, respectively. CCT241161 shows good activity to in BRAF and NRAS mutant melanomas. CCT241161 also exhibits anticancer cell proliferative activity[1].

  • CAS Number: 1163719-91-2
  • MF: C28H27N7O3S
  • MW: 541.624
  • Catalog: Apoptosis
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A