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.


Anti-infection >
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Antibody-drug Conjugate >
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Apoptosis >
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15-PGDH 5 alpha Reductase 5-Lipoxygenase Acetyl-CoA Carboxylase Acyltransferase Adenosine Deaminase Adenosine Kinase Aldehyde Dehydrogenase (ALDH) Aldose Reductase Aminopeptidase Angiotensin-converting Enzyme (ACE) ATGL ATP Citrate Lyase Carbonic Anhydrase Carboxypeptidase Cathepsin CETP COMT Cytochrome P450 Dipeptidyl Peptidase Dopamine β-hydroxylase E1/E2/E3 Enzyme Elastase Enolase FAAH FABP Factor Xa Farnesyl Transferase Fatty Acid Synthase (FAS) FXR Glucokinase GSNOR Gutathione S-transferase HCV Protease Hexokinase HIF/HIF Prolyl-Hydroxylase HIV Integrase HIV Protease HMG-CoA Reductase (HMGCR) HSP Indoleamine 2,3-Dioxygenase (IDO) Isocitrate Dehydrogenase (IDH) Lactate Dehydrogenase LXR MAGL Mineralocorticoid Receptor Mitochondrial Metabolism MMP Nampt NEDD8-activating Enzyme Neprilysin PAI-1 PDHK PGC-1α Phosphatase Phosphodiesterase (PDE) Phospholipase Procollagen C Proteinase Proteasome Pyruvate Kinase RAR/RXR Renin ROR Ser/Thr Protease SGK Stearoyl-CoA Desaturase (SCD) Thrombin Tryptophan Hydroxylase Tyrosinase Xanthine Oxidase
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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

CAY10756

ASK1-IN-1 is a CNS-penetrant ASK1 (apoptosis signal-regulating kinase 1) inhibitor, with good potency (cell IC50=138 nM; Biochemical IC50=21 nM)[1].

  • CAS Number: 2411382-24-4
  • MF: C19H19N9O2
  • MW: 405.41
  • Catalog: p38 MAPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HPK1-IN-20

HPK1-IN-19 is a hematopoietic progenitor kinase 1 (HPK1) inhibitor extracted from patent WO2020235902A1 compound 106[1].

  • CAS Number: 2561490-78-4
  • MF: C26H28N6O2
  • MW: 456.54
  • Catalog: MAP4K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

HPK1 antagonist-1

HPK1 antagonist-1 (I-792) is an Hpk1 antagonist that can be used in the study of cancer and immune disease[1].

  • CAS Number: 2628489-56-3
  • MF: C28H29FN6O2
  • MW: 500.57
  • Catalog: MAP4K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MAPK13-IN-1

MPAK13-IN-1 is a MAPK13 (p38δ) inhibitor, with an IC50 of 620 nM.

  • CAS Number: 229002-10-2
  • MF: C20H23N5O2
  • MW: 365.43
  • Catalog: p38 MAPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MNK inhibitor 9

MNK inhibitor 9 is a potent, selective MAPK-interacting kinase (MNK1 and MNK2) inhibitor with IC50 of 3 nM for both, with no activity aginst CDK1/2 (IC50>25 uM); displays excellent selectivity against a 53 kinase panel, with 4 kinases with IC50 <1 uM; inhibits eIF4E phosphorylation in KMS11-luc myeloma with IC50 of 0.6 nM, exhibits inhibition of cell proliferation in human multiple myeloma tumor cell line with EC50 of 1.7 uM; has good solubility and permeability, and is a suitable in vivo tool compound.

  • CAS Number: 1889336-59-7
  • MF: C25H29N9O
  • MW: 471.569
  • Catalog: MNK
  • 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

MCP110

MCP110 is an inhibitor of Ras/Raf-1 interaction. MCP110 blocks the interaction of Ras with Raf[1].

  • CAS Number: 521310-51-0
  • MF: C33H36N2O3
  • MW: 508.651
  • Catalog: Ras
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 686.3±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 368.8±31.5 °C

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

3′-O-Demethyl-4′-N-demethyl-4′-N-acetyl-4′-epi-staurosporine

3′-O-Demethyl-4′-N-demethyl-4′-N-acetyl-4′-epi-staurosporine (Compound 7) is an inhibitor of protein kinases, with IC50s of 0.092, 0.26, 0.77 μM for PKC-α, ROCK, ASK1. 3′-O-Demethyl-4′-N-demethyl-4′-N-acetyl-4′-epi-staurosporine shows potent cytotoxicity against PC-3 cancer cells with an IC50 value of 0.16 μM[1].

  • CAS Number: 2226941-29-1
  • MF: C28H24N4O4
  • MW: 480.51
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

RLX-33

RLX-33 is a potent, selective and blood-brain barrier (BBB) penetrant relaxin family peptide 3 (RXFP3) antagonist, also blocks relaxin-3-induced ERK1/2 phosphorylation, with IC50 values of 2.36 μM for RXFP3, 7.82 and 13.86 μM for ERK1 and ERK2 phosphorylation, respectively. RLX-33 can block the stimulation of food intake induced by the RXFP3-selective agonist R3/I5 in rats. RLX-33 can be used for the research of metabolic syndrome[1].

  • CAS Number: 2784577-71-3
  • MF: C24H19ClN4O4
  • MW: 462.89
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

5,6,7,15-tetrahydroxy-17-methoxy-11-methyl-12-oxabicyclo[12.4.0]octadeca-1(14),2,8,15,17-pentaen-13-one

LL-Z1640-4 is a potent p38/JNK signaling inhibitor. LL-Z1640-4 significantly diminishes p38 and JNK activation in HCC cells transfected with MLK4 siRNA. LL-Z1640-4 markedly attenuates ROS production induced by MLK4 knockdown. LL-Z1640-4 significantly reduces the apoptotic cells in HCC cells transfected with siMLK4[1][2].

  • CAS Number: 66018-41-5
  • MF: C19H24O7
  • MW: 364.39000
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

DMX-5804

DMX-5804 is a potent, orally active and selective MAP4K4 inhibitor, with an IC50 of 3 nM, a pIC50 of 8.55 for human MAP4K4, less potent on MINK1/MAP4K6 (pIC50, 8.18), and TNIK/MAP4K7 (pIC50, 7.96). DMX-5804 enhances cardiomyocyte survival, and reduces ischemia-reperfusion injury in mice[1].

  • CAS Number: 2306178-56-1
  • MF: C21H19N3O3
  • MW: 361.39
  • Catalog: MAP4K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

Juglanin

Juglanin is a JNK activator.

  • CAS Number: 5041-67-8
  • MF: C20H18O10
  • MW: 418.351
  • Catalog: JNK
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: 803.5±65.0 °C at 760 mmHg
  • Melting Point: 230-231℃ (ethanol )
  • Flash Point: 289.0±27.8 °C

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

Enniatin B1

Enniatin B1 is a Fusarium mycotoxin. Enniatin B1 inhibits acyl-CoA: cholesterol acyltransferase (ACAT) activity with an IC50 of 73 μM in an enzyme assay using rat liver microsomes[1]. Enniatin B1 crosss the blood-brain barrier[2]. Enniatin B1 decreases the activation of ERK (p44/p42). Enniatin B1 inhibits moderately TNF-α-induced NF-κB activation[3].

  • CAS Number: 19914-20-6
  • MF: C34H59N3O9
  • MW: 653.847
  • Catalog: ERK
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 833.8±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 458.0±34.3 °C

RSK-IN-1

RSK-IN-1 (compound 7d) is a RSK inhibitor that inhibits the YB-1 phosphorylation. RSK-IN-1 has anti-tumor effects[1].

  • CAS Number: 2761698-77-3
  • MF: C22H17NO2
  • MW: 327.38
  • Catalog: Ribosomal S6 Kinase (RSK)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-05381941

PF-05381941 (PF 05381941, PF05381941) is a potent, dual TAK1/p38a inhibitor with IC50 of 156/186 nM respectively, with good kinome selectivity against 50 representative kinases; inhibits LPS-stimulated release of TNF-α from human peripheral mononuclear cells with IC50 of 8 nM.

  • CAS Number: 1474022-02-0
  • MF: C27H26N6O2
  • MW: 466.545
  • Catalog: MAP3K
  • 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