Metabolic pathways are enzyme-mediated biochemical reactions that lead to biosynthesis (anabolism) or breakdown (catabolism) of natural product small molecules within a cell or tissue. In each pathway, enzymes catalyze the conversion of substrates into structurally similar products. Metabolic processes typically transform small molecules, but also include macromolecular processes such as DNA repair and replication, and protein synthesis and degradation. Metabolism maintains the living state of the cells and the organism.

Proteases are used throughout an organism for various metabolic processes. Proteases control a great variety of physiological processes that are critical for life, including the immune response, cell cycle, cell death, wound healing, food digestion, and protein and organelle recycling. On the basis of the type of the key amino acid in the active site of the protease and the mechanism of peptide bond cleavage, proteases can be classified into six groups: cysteine, serine, threonine, glutamic acid, aspartate proteases, as well as matrix metalloproteases. Proteases can not only activate proteins such as cytokines, or inactivate them such as numerous repair proteins during apoptosis, but also expose cryptic sites, such as occurs with β-secretase during amyloid precursor protein processing, shed various transmembrane proteins such as occurs with metalloproteases and cysteine proteases, or convert receptor agonists into antagonists and vice versa such as chemokine conversions carried out by metalloproteases, dipeptidyl peptidase IV and some cathepsins. In addition to the catalytic domains, a great number of proteases contain numerous additional domains or modules that substantially increase the complexity of their functions.

Imbalances in metabolic activities have been found to be critical in a number of pathologies, such as cardiovascular diseases, inflammation, cancer, and neurodegenerative diseases.

References:
[1] Turk B, et al. EMBO J. 2012 Apr 4;31(7):1630-43.
[2] Eatemadi A, et al. Biomed Pharmacother. 2017 Feb;86:221-231.


Anti-infection >
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Antifolate APC ATM/ATR Aurora Kinase Casein Kinase CDK Checkpoint Kinase (Chk) CRISPR/Cas9 Deubiquitinase DNA Alkylator/Crosslinker DNA-PK DNA/RNA Synthesis Eukaryotic Initiation Factor (eIF) G-quadruplex Haspin Kinase HDAC HSP IRE1 Kinesin LIM Kinase (LIMK) Microtubule/Tubulin Mps1 Nucleoside Antimetabolite/Analog p97 PAK PARP PERK Polo-like Kinase (PLK) PPAR RAD51 ROCK Sirtuin SRPK Telomerase TOPK Topoisomerase Wee1
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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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HIF-2α-IN-2

HIF-2α-IN-2 is a hypoxia-inducible factors (HIF-2α) inhibitor extracted from patent WO2015035223A1, Compound 232, has an IC50 of 16 nM in scintillation proximity assay (SPA)[1].

  • CAS Number: 1672666-82-8
  • MF: C17H13F2NO4S
  • MW: 365.35
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: 1.52±0.1 g/cm3(Predicted)
  • Boiling Point: 530.6±50.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

beta-Amyrin palmitate

β-Amyrin palmitate shows HMG-CoA reductase inhibition[1]. And β-Amyrin palmitate has anti-diabetes mellitus activity[2].

  • CAS Number: 5973-06-8
  • MF: C46H80O2
  • MW: 665.13
  • Catalog: HMG-CoA Reductase (HMGCR)
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 661.4±54.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 354.1±18.8 °C

AZD7687

AZD7687 is a potent and selective DGAT1 inhibitor with an IC50 value of 80 nM (hDGAT1).IC50 value: 80 nM [1]Target: DGAT1in vitro: Plasma AZD7687 exposure was measured repeatedly. Postprandial serum TAG excursion was measured during 8 h after a standardized mixed meal with fat energy content of 60% (SMM 60%; five cohorts, 1-20 mg), before (baseline) and after dosing, to assess effects on gut DGAT1 activity. AZD7687 markedly reduced postprandial TAG excursion with a steep concentration-effect relationship [2].in vivo: Multiple doses of AZD7687 (1, 2.5, 5, 10 and 20 mg/day, n=6 or n=12 for each) or placebo (n=20) were administered for 1 week. Dose-dependent reductions in postprandial serum TAG were demonstrated with AZD7687 doses ≥5mg compared with placebo (p<0.01). Significant (p<0.001) increases in plasma GLP-1 and PYY levels were seen at these doses, but no clear effect on gastric emptying was demonstrated at the end of treatment. With AZD7687 doses >5 mg/day, gastrointestinal (GI) side effects increased; 11/18 of these participants discontinued treatment owing to diarrhoea [3].

  • CAS Number: 1166827-44-6
  • MF: C21H25N3O3
  • MW: 367.44200
  • Catalog: Acyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Alda 1

Alda-1 is a potent ALDH2 agonist, which activates wild-type ALDH2 and restores near wild-type activity to ALDH2*2.

  • CAS Number: 349438-38-6
  • MF: C15H11Cl2NO3
  • MW: 324.15900
  • Catalog: Aldehyde Dehydrogenase (ALDH)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Etazolate hydrochloride

Etazolate hydrochloride (SQ 20009) is an orally active, selective inhibitor of type 4 phosphodiesterase (PDE4) with an IC50 of 2 μM. Etazolate hydrochloride is a γ-aminobutyric acid A (GABAA) receptor regulator. Etazolate hydrochloride is an α-secretase activator and induced the production of soluble amyloid precursor protein (sAPPα). Etazolate hydrochloride, a pyrazolopyridine class derivative, increases cAMP levels. Etazolate hydrochloride has anxiolyticlike, antidepressant-like and anti-inflammatory effects[1][2][3][4][5].

  • CAS Number: 35838-58-5
  • MF: C14H20ClN5O2
  • MW: 325.79400
  • Catalog: GABA Receptor
  • Density: 1.25g/cm3
  • Boiling Point: 427.6ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 212.4ºC

Isoeuphorbetin

Isoeuphorbetin, a dimeric coumarin isolated from Viola philippica, is a potent HCV protease inhibitor with an IC50 of 3.63 µg/mL[1].

  • CAS Number: 50886-61-8
  • MF: C18H10O8
  • MW: 354.26700
  • Catalog: HCV Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sinapic acid

Sinapinic acid (Sinapic acid) is a phenolic compound isolated from Hydnophytum formicarum Jack. Rhizome, acts as an inhibitor of HDAC, with an IC50 of 2.27 mM[1], and also inhibits ACE-I activity[2]. Sinapinic acid posssess potent anti-tumor activity, induces apoptosis of tumor cells[1]. Sinapinic acid shows antioxidant and antidiabetic activities[2]. Sinapinic acid reduces total cholesterol, triglyceride, and HOMA-IR index, and also normalizes some serum parameters of antioxidative abilities and oxidative damage in ovariectomized rats[3].

  • CAS Number: 530-59-6
  • MF: C11H12O5
  • MW: 224.210
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 403.4±40.0 °C at 760 mmHg
  • Melting Point: 203-205 °C (dec.)(lit.)
  • Flash Point: 158.6±20.8 °C

NCT-505

NCT-505 is a potent and selective aldehyde dehydrogenase (ALDH1A1) inhibitor, with an IC50 of 7 nM, and weakly inhibits hALDH1A2, hALDH1A3, hALDH2, hALDH3A1 (IC50s, >57, 22.8, 20.1, >57 μM).

  • CAS Number: 2231079-74-4
  • MF: C27H28FN5O3S
  • MW: 521.61
  • Catalog: Aldehyde Dehydrogenase (ALDH)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FK-448 Free base

FK-448 Free base is an effective and specific inhibitor of chymotrypsin, with an IC50 of 720 nM.

  • CAS Number: 85858-76-0
  • MF: C25H30N2O3
  • MW: 406.52
  • Catalog: Proteasome
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4-Ethynyl-L-phenylalanine hydrochloride

4-Ethynyl-L-phenylalanine hydrochloride is a selective, reversible, potent and competitive inhibitor of tryptophan hydroxylase (TPH). 4-Ethynyl-L-phenylalanine hydrochloride is a competitive inhibitor with regard to the substrate tryptophan, with a Ki of 32.6 μM. 4-Ethynyl-L-phenylalanine hydrochloride selectively and reversibly inhibits the biosynthesis of serotonin[1].

  • CAS Number: 188640-63-3
  • MF: C11H12ClNO2
  • MW: 225.67
  • Catalog: Tryptophan Hydroxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

K134

K134 is a phosphodiesterase 3 (PDE3) inhibitor. The IC50s of K134 toward PDE3A, PDE3B, PDE5, PDE2 and PDE4 are 0.1, 0.28, 12.1, >300 and >300 µM, respectively.

  • CAS Number: 189362-06-9
  • MF: C22H29N3O4
  • MW: 399.48300
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PD125754

PD125754 is an oligopeptide renin inhibitor (IC50: 22 nM)[1].

  • CAS Number: 124339-32-8
  • MF: C42H65N5O7
  • MW: 751.99500
  • Catalog: Renin
  • Density: 1.14g/cm3
  • Boiling Point: 993.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 554.5ºC

VU 0364739 hydrochloride

VU 0364739 hydrochloride is a highly selective phospholipase D2 (PLD2) inhibitor with IC50s of 20 and 1500 nM for PLD2 and PLD1, respectively. VU 0364739 hydrochloride induces apoptosis and it can be used for cancer research[1].

  • CAS Number: 1244640-48-9
  • MF: C26H28ClFN4O2
  • MW: 482.978
  • Catalog: Phospholipase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Taraxerone

Taraxerone is isolated from Sedum sarmentosum. Taraxerone enhances effects on alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activities with EC50 values of 512.42 and 500.16 μM, respectively[1].

  • CAS Number: 514-07-8
  • MF: C30H48O
  • MW: 424.702
  • Catalog: Aldehyde Dehydrogenase (ALDH)
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 488.3±44.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 202.8±23.4 °C

danshenol A

Danshenol A, an abietane-type diterpenoid, is an aldose reductase (AR) inhibitor with an IC50 of 0.1 μM. Danshenol A can protect endothelial cells from oxidative stress by directly scavenging ROS. Danshenol A has anti-inflammatory and antitumor properties. Danshenol A can be used for atherosclerosis research[1][2][3][4].

  • CAS Number: 189308-08-5
  • MF: C21H20O4
  • MW: 336.38100
  • Catalog: Aldose Reductase
  • Density: 1.31±0.1 g/cm3
  • Boiling Point: 571.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 206.6ºC

Phaeosphaone D

Phaeosphaone D is a thiodiketopiperazine alkaloid compound isolated from Phaeosphaeria fuckelii, an endophytic fungus. Phaeosphaone D displays mushroom tyrosinase inhibitory activity with an IC50 value of 33.2 μM[1].

  • CAS Number: 2640137-78-4
  • MF: C20H27N3O3S2
  • MW: 421.58
  • Catalog: Tyrosinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sitagliptin fenilalanil

Sitagliptin fenilalanil is a dipeptidyl aminopeptidase 4 (DPP-4) inhibitor[1].

  • CAS Number: 1339955-03-1
  • MF: C25H24F6N6O2
  • MW: 554.49
  • Catalog: Dipeptidyl Peptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ABT-702 dihydrochloride

ABT-702 dihydrochloride is a potent adenosine kinase (AK) inhibitor (IC50=1.7 nM).

  • CAS Number: 1188890-28-9
  • MF: C22H21BrCl2N6O
  • MW: 536.252
  • Catalog: Adenosine Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mca-PLGL-Dpa-AR-NH2

Mca-PLGL-Dpa-AR-NH2 is a fluorescent peptide MMP substrate[1].

  • CAS Number: 1135689-33-6
  • MF: C43H66N12O11
  • MW: 927.06
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nortadalafil

Nortadalafil is demethyl Tadalafil, which is a PDE5 inhibitor, currently marketed in pill form for treating erectile dysfunction (ED) under the name Cialis; and under the name Adcirca for the treatment of pulmonary arterial hypertension.IC50 value:Target:

  • CAS Number: 171596-36-4
  • MF: C21H17N3O4
  • MW: 375.377
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 718.6±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 388.4±32.9 °C

Phenidone

Phenidone, an orally active dual inhibitor of cyclooxygenase (COX) and lipoxygenase (LOX), ameliorates rat paralysis in experimental autoimmune encephalomyelitis. Phenidone is a potent hypotensive agent in the spontaneously hypertensive rat[1][2]. Phenidone is used as a photographic developer[3].

  • CAS Number: 92-43-3
  • MF: C9H10N2O
  • MW: 162.189
  • Catalog: COX
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 304.1±25.0 °C at 760 mmHg
  • Melting Point: 119-121 °C(lit.)
  • Flash Point: 137.7±23.2 °C

RORγt inverse agonist 30

RORγt inverse agonist 30 (Compound 1) is a potent RORγt inverse agonist with the IC50 of 46 nM. Targeting the nuclear receptor RORγt is effective in autoimmune disorders[1].

  • CAS Number: 1445901-41-6
  • MF: C24H31N3O3S
  • MW: 441.59
  • Catalog: ROR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pyributicarb

Pyributicarb, a carbamate-type herbicide, is a potent activator of both CYP3A4 gene and human pregnane X receptor (hPXR).

  • CAS Number: 88678-67-5
  • MF: C18H22N2O2S
  • MW: 330.444
  • Catalog: Cytochrome P450
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 427.8±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 212.5±31.5 °C

KLK7/ELA2-IN-1

KLK7/ELA2-IN-1 is a potent kallikrein-related peptidase 7 (KLK7) and epidermal elastase 2 (ELA2) inhibitor with IC50s of 6 nM and 55 nM, respectively (WO2009024527A1, Example 4)[1].

  • CAS Number: 1122484-55-2
  • MF: C46H72N8O12
  • MW: 929.11
  • Catalog: Elastase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CYP3A4-IN-1

CYP3A4-IN-1 (compound 5a) is a potent cytochrome P450 3A4 (CYP3A4) inhibitor with an IC50 value of 0.085 µM[1].

  • CAS Number: 2771297-34-6
  • MF: C31H37N5O3S
  • MW: 559.72
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VBY-825

VBY-825 is a novel, reversible cathepsin inhibitor with high potency against cathepsins B, L, S and V.IC50 value: Target: 130/250/250/330/2.3/4.7 nM(Ki for cathepsin S/L/ZV/Bhumanized-rabbit cathepsin K/cathepsin F) [1]VBY-825 is a potent inhibitor of the assayed cathepsins and its potency against at least one cathepsin, cathepsin S, extends across species relevant for pharmacology studies, specifically mouse. 10 mg/kg/day dose of VBY-825 achieves a trough plasma concentration >200nM, which is well above that required for full inhibition of the intracellular activity of cathepsins B, F, K, L, S and V in both mouse and human cell lines.

  • CAS Number: 1310340-58-9
  • MF: C23H29F4N3O5S
  • MW: 535.55200
  • Catalog: Cathepsin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SHP836

SHP836 is a distinct, allosteric site 2 SHP2 inhibitor with IC50 of 12 uM (SHP2 1-525), and selective over the phosphatase domain (SHP2 PTP IC50>100 uM).downregulates DUSP6 mRNA, a downstream MAPK pathway marker, in KYSE-520 cancer cells; enhances pharmacological pathway inhibition in cells combined with SHP099.

  • CAS Number: 1957276-35-5
  • MF: C16H19Cl2N5
  • MW: 352.263
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

Gymnestrogenin

Gymnestrogenin is a pentahydroxytriterpene from the leaves of Gymnema sylvestre R.Br[1]. Gymnestrogenin is a LXR antagonist with IC50s of 2.5 and 1.4 μM for LXRα and LXRβ transactivation, respectively. Gymnestrogenin reduces the transcriptional activity of LXR even on its own promoter, thus reducing the mRNA expression[2].

  • CAS Number: 19942-02-0
  • MF: C30H50O5
  • MW: 490.71500
  • Catalog: LXR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 288-289 °C
  • Flash Point: N/A

GYKI 47261 dihydrochloride

GYKI-47261 dihydrochloride is a competitive, orally active, and selective AMPA receptor antagonist with an IC50 of 2.5 μM. GYKI-47261 has broad spectrum anticonvulsive activity and neuroprotective effects. GYKI-47261 dihydrochloride is also a potent inducer of CYP2E1[1][2].

  • CAS Number: 1217049-32-5
  • MF: C18H17Cl3N4
  • MW: 395.713
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A