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.


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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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NCT-506

NCT-506 is an orally bioavailable aldehyde dehydrogenase 1A1 (ALDH1A1) inhibitors with an IC50 of 7 nM[1].

  • CAS Number: 2231098-99-8
  • MF: C25H23FN4O3S
  • MW: 478.54
  • Catalog: Aldehyde Dehydrogenase (ALDH)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BI-4394

BI-4394 is a highly potent, selective MMP-13 inhibitor with IC50 of 1 nM, displays >1,000 fold selectivity against nine other MMP isoforms (MMP2/14, IC50=18/8.3 uM); BI-4394 is potent in a full-length MMP-13 collagen degradation assay (IC50=11 nM) and is able to inhibit degradation of bovine nasal cartilage with an IC50 of 31 nM.

  • CAS Number: 1222173-37-6
  • MF: C24H22N4O5
  • MW: 446.455
  • Catalog: MMP
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 764.4±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 416.1±32.9 °C

Pravastatin (sodium)

Pravastatin sodium is an HMG-CoA reductase inhibitor against sterol synthesis with IC50 of 5.6 μM.Target: HMG-CoA reductasePravastatin (marketed as Pravachol or Selektine) is a member of the drug class of statins, used in combination with diet, exercise, and weight-loss for lowering cholesterol and preventing cardiovascular disease.Pravastatin is primarily used for the treatment of dyslipidemia and the prevention of cardiovascular disease. It is recommended to be used only after other measures such as diet, exercise, and weight reduction have not improved cholesterol levels.The evidence for the use of pravastatin is generally weaker than for other statins. The antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT), failed to demonstrate a difference in all-cause mortality or nonfatal myocardial infarction/fatal coronary heart disease rates between patients receiving pravastatin 40mg daily (a common starting dose) and those receiving usual care.

  • CAS Number: 81131-70-6
  • MF: C23H35NaO7
  • MW: 446.51
  • Catalog: Ferroptosis
  • Density: N/A
  • Boiling Point: 634.5ºCat 760 mmHg
  • Melting Point: 171.2-173 °C
  • Flash Point: 213.2ºC

NLG919

IDO-IN-7 (NLG-919 analogue) is a a potent IDO1 inhibitor with an IC50 of 38 nM.

  • CAS Number: 1402836-58-1
  • MF: C18H22N2O
  • MW: 282.380
  • Catalog: Indoleamine 2,3-Dioxygenase (IDO)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 524.6±33.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 271.1±25.4 °C

Chrysophanol triglucoside

Chrysophanol triglucoside is an anthraquinone isolated from Cassia obtusifolia, inhibits protein tyrosine phosphatases 1B (PTP1B) and α-glucosidase with IC50s of 80.17 and 197.06 µM, respectively. Chrysophanol triglucoside has the potential for diabetes research[1].

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

SR3335

SR3335 is a selective RORα synthetic ligand, directly binds to RORα (Ki 220 nM) but not other RORs, and functions as a selective partial inverse agonist of RORα in cell-based assays.

  • CAS Number: 293753-05-6
  • MF: C13H9F6NO3S2
  • MW: 405.336
  • Catalog: ROR
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 465.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 235.3±31.5 °C

1-Ethynylnaphthalene

1-Ethynylnaphthalene is a selective inhibitor of cytochrome P450 1B1.

  • CAS Number: 15727-65-8
  • MF: C12H8
  • MW: 152.19200
  • Catalog: Cytochrome P450
  • Density: 1.070 g/mL at 25ºC(lit.)
  • Boiling Point: 270.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 106.3ºC

RV01

RV01 is an analogue of resveratrol, inhibits DNA damage, reduces acetaldehyde dehydrogenase 2 (ALDH2) mRNA expression induced by ethanol, and exhibits hydroxyl radical scavenging activity[1]. RV01 decreases iNOS expression, with anti-neuroinflammatory activity[2].

  • CAS Number: 1016897-10-1
  • MF: C17H13NO2
  • MW: 263.29
  • Catalog: Aldehyde Dehydrogenase (ALDH)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Benzenecarboximidamide hydrochloride hydrate

Benzenecarboximidamide, hydrochloride, hydrate (1:1:x) (Benzamidine hydrochloride hydrate) is a reversible competitive trypsin-like serine proteases inhibitor with Kis of 20, 21, 97, 110, 320 and 750 μM against Tryptase, Trypsin, uPA, Factor Xa, Thrombin and tPA, respectively[1][2].

  • CAS Number: 206752-36-5
  • MF: C7H8N2.ClH.xH2O
  • MW: 174.628
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: 208.5ºC at 760mmHg
  • Melting Point: 86-88 °C(lit.)
  • Flash Point: 79.9ºC

halazone

Halazone is an atypical antimicrobial sulfonamide derivative and a carbonic anhydrase II inhibitor with a Kd value of 1.45 µM. Halazone protects sodium channels from inactivation. Halazone is widely used for disinfection of drinking water[1][2].

  • CAS Number: 80-13-7
  • MF: C7H5Cl2NO4S
  • MW: 270.09000
  • Catalog: Bacterial
  • Density: 1.717 g/cm3
  • Boiling Point: 437ºC at 760 mmHg
  • Melting Point: 213ºC
  • Flash Point: 218.1ºC

Ac-Asp(Glu-OH)-OH

β-Spaglumic acid (β-NAAG) is a competitive NAAG peptidase inhibitor (Ki=1 µM) that protects spinal cord neurons from excitotoxicity and hypoxic damage. β-Spaglumic acid is also a selective mGluR3 antagonist (mGluR3 receptor functions to regulate activity-dependent synaptic potentiation in the hippocampus). β-Spaglumic acid can be used in neuroprotection-related studies[1][2].

  • CAS Number: 4910-46-7
  • MF: C11H16N2O8
  • MW: 304.253
  • Catalog: mGluR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 769.5±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 419.1±32.9 °C

PRT 4165

PRT4165 is a potent inhibitor of PRC1-mediated H2A ubiquitylation.

  • CAS Number: 31083-55-3
  • MF: C15H9NO2
  • MW: 235.238
  • Catalog: E1/E2/E3 Enzyme
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 452.3±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 227.0±35.1 °C

Enpp-1-IN-13

Enpp-1-IN-13 (Compound 1a) is an ectonucleotide pyrophosphatase/phosphodiesterase (ENPP) inhibitor with IC50 values of 1.29 μM and 20.2 μM against ENPP1 and ENPP3, respectively. Enpp-1-IN-13 shows anticancer activity[1].

  • CAS Number: 2417022-19-4
  • MF: C28H22ClN5OS
  • MW: 512.03
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VII-31

VII-31 is a potent NEDDylation pathway activator to inhibit the tumor progression in vitro and in vivo. VII-31 induces apoptosis via intrinsic and extrinsic pathways[1].

  • CAS Number: 2305757-96-2
  • MF: C23H25NO5S
  • MW: 427.51
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L-(+)-Leucinol

L-Leucinol ((+)-Leucinol) is a competitive aminopeptidase inhibitor with Ki value of 17 μM[1].

  • CAS Number: 7533-40-6
  • MF: C6H15NO
  • MW: 117.189
  • Catalog: Aminopeptidase
  • Density: 0.917
  • Boiling Point: 208-210 ºC
  • Melting Point: 66 - 70ºC
  • Flash Point: 90 ºC

NS5A-IN-4

NS5A-IN-4 (Compound 1.12) is an orally active pan-genotypic hepatitis C virus (HCV) NS5A inhibitor with IC50 values of 1.2, 2296, 4.6, 362, 10.3 and 693 pM against gT1b, gT1a, gT2a, gT3a, gT4a and gT5a[1].

  • CAS Number: 2088243-03-0
  • MF: C47H48N8O6
  • MW: 820.93
  • Catalog: HCV Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BC-1382

A potent ubiquitin E3 ligase HECTD2 inhibitor that specificly disrupts the HECTD2/PIAS1 interaction with IC50 of 5 nM; drastically increases PIAS1 protein level with IC50 of 100 nM and improves PIAS1 protein stability, with no effect on PIAS3, PIAS4, and HECTD2 protein levels; suppresses LPS-induced PIAS1 degradation and restores PIAS1 protein levels at 800 nM, and proinflammatory cytokines released by PBMCs; attenuates LPS- and Pseudomonas aeruginosa-induced lung inflammation

  • CAS Number: 1013753-99-5
  • MF: C23H29N3O5S
  • MW: 459.559
  • Catalog: E1/E2/E3 Enzyme
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lopinavir-d8

Lopinavir-d8 (ABT-378-d8) is the deuterium labeled Lopinavir. Lopinavir (ABT-378) is a highly potent, selective peptidomimetic inhibitor of the HIV-1 protease, with Kis of 1.3 to 3.6 pM for wild-type and mutant HIV protease. Lopinavir acts by arresting maturation of HIV-1 thereby blocking its infectivity[1][2]. Lopinavir is also a SARS-CoV 3CLpro inhibitor with an IC50 of 14.2 μM[3].

  • CAS Number: 1224729-35-4
  • MF: C37H40D8N4O5
  • MW: 636.85
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aminohexylgeldanamycin hydrochloride

Aminohexylgeldanamycin (AHGDM) hydrochloride, a Geldanamycin derivative, is a potent HSP90 inhibitor. Aminohexylgeldanamycin hydrochloride shows antiangiogenic and antitumor activities[1].

  • CAS Number: 1146534-45-3
  • MF: C34H53ClN4O8
  • MW: 681.26
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mesembrine-d3

Mesembrine-d3 ((+)-Mesembrine-d3) is the deuterium labeled Mesembrine. Mesembrine ((+)-Mesembrine) a main alkaloid that features an aryloctahydroindole skeleton. Mesembrine is a 5-HT transporter inhibitor with a Ki of 1.4 nM. Mesembrine also inhibits phosphodiesterase 4B (PDE4B) with an IC50 of 7.8 μM[1][2].

  • CAS Number: 1346600-05-2
  • MF: C17H20D3NO3
  • MW: 292.39
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Xanthine oxidase-IN-1

Xanthine oxidase-IN-1 is a xanthine oxidase inhibitor extracted from patent WO2008126898A1, page 68, compound example 3, with an IC50 of 6.5 nM.

  • CAS Number: 1071970-13-2
  • MF: C16H8F2N2O3
  • MW: 314.24
  • Catalog: Xanthine Oxidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DHODH-IN-8

DHODH-IN-8 (Compound 27) is an inhibitor of human and Plasmodium falciparum dihydroorotate dehydrogenase (DHODH) with IC50s of 0.13 μM and 47.4 μM, and Kis of 0.016 μM and 5.6 μM, respectively. DHODH-IN-8 has antimalarial activity[1].

  • CAS Number: 1148126-03-7
  • MF: C17H13ClN2O2
  • MW: 312.75
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FT113

FT113 is a potent and orally active fatty acid synthase (FASN) inhibitor, with an IC50 of 213 nM for full-length recombinant human FASN enzyme. In cell-based assay, FT113 blocks FASN activity in BT474 cells (IC50, 90 nM). FT113 shows anti-proliferative activity, and exhibits anti-cancer both in vitro and in vivo[1].

  • CAS Number: 1630808-89-7
  • MF: C22H20FN3O4
  • MW: 409.41
  • Catalog: Fatty Acid Synthase (FAS)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KAR-5417

Rodatristat (KAR5417) is a potent tryptophan hydroxylase 1 (TPH1) inhibitor with an IC50 value of 33 nM, and shows robust reduction of intestinal serotonin (5-HT) levels in mice. Rodatristat also shows potent inhibition of TPH2 (IC50 of 7 nM)[1].

  • CAS Number: 1673568-73-4
  • MF: C27H27ClF3N5O3
  • MW: 561.98
  • Catalog: Tryptophan Hydroxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Arasertaconazole

Arasertaconazole is a potent 14α-lanosterol demethylase inhibitor. Arasertaconazole has antifungal and antibacterial activity[1].

  • CAS Number: 583057-48-1
  • MF: C20H15Cl3N2OS
  • MW: 437.77000
  • Catalog: Bacterial
  • 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

edoxaban tosylate

Edoxaban(DU-176) is an oral factor Xa (FXa) inhibitor in clinical development for stroke preventionIC50 Value:Target: factor XaEdoxaban is an oral factor Xa (FXa) inhibitor in clinical development for stroke prevention in patients with atrial fibrillation, an elderly population that frequently receives aspirin (ASA) and/or nonsteroidal anti-inflammatory drugs for concurrent illnesses[1].in vitro: Edoxaban PK was not affected by concomitant low-dose ASA or naproxen, but high-dose ASA increased systemic exposure of edoxaban by approximately 30%. The effects of edoxaban on prothrombin time, activated partial thromboplastin time, international normalized ratio, anti-FXa, and intrinsic FXa activity were not influenced by administration with ASA or naproxen. Inhibition of platelet aggregation by high-dose ASA, low-dose ASA, or naproxen was not affected by edoxaban[1].in vivo: Forty-eight subjects, aged 18 to 45 years, received either edoxaban 60 mg once daily × 7 days (n = 24) or digoxin 0.25 mg twice daily × 2 days and once daily × 5 days (n = 24) and then concomitantly for 7 days. Serial blood and urine samples were collected for digoxin and edoxaban concentrations on days 7 and 14. Serial coagulation assays were measured for edoxaban on days 7 and 14. Edoxaban PK parameters demonstrated mild increases in area under the curve and peak concentrations of 9.5% and 15.6%, respectively[2],Clinical trial: Pharmacokinetics, biotransformation, and mass balance of edoxaban, a selective, direct factor Xa inhibitor, in humans was reported[3].

  • CAS Number: 480449-71-6
  • MF: C31H38ClN7O7S2
  • MW: 720.259
  • Catalog: Factor Xa
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-429242

PF429242 is a reversible and competitive SREBP site 1 protease (S1P) inhibitor with an IC50 of 175 nM[1].

  • CAS Number: 947303-87-9
  • MF: C25H35N3O2
  • MW: 409.56
  • Catalog: Fatty Acid Synthase (FAS)
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 562.2±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 293.8±30.1 °C

Bortezomib (PS-341)

Bortezomib (PS-341) is a potent 20S proteasome inhibitor with a Ki of 0.6 nM.

  • CAS Number: 179324-69-7
  • MF: C19H25BN4O4
  • MW: 384.237
  • Catalog: Autophagy
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 122-124°C
  • Flash Point: N/A

Celastrol

Tripterin (Celastrol) is a proteasome inhibitor which potently and preferentially inhibits the chymotrypsin-like activity of a purified 20S proteasome with IC50 of 2.5 μM.

  • CAS Number: 34157-83-0
  • MF: C29H38O4
  • MW: 450.610
  • Catalog: Autophagy
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 645.7±55.0 °C at 760 mmHg
  • Melting Point: 185-200ºC
  • Flash Point: 358.3±28.0 °C