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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CAY10499

MAGL-IN-5 is a non-selective lipase inhibitor with IC50 values of 144, 90, and 14 nM for human recombinant monoacylglycerol lipase(MAGL),hormone sensitive lipase(HSL), and fatty acid amide hydrolase(FAAH) respectively[1][2].

  • CAS Number: 359714-55-9
  • MF: C18H17N3O5
  • MW: 355.345
  • Catalog: FAAH
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-(4-(2-Amino-2-oxoethoxy)-1-benzyl-2-ethyl-1H-indol-3-yl)-2-oxoacetamide

hnps-PLA-IN-1 (compound 5aa), a indole-3-acetamide, is a hnps-PLA2 inhibitor (IC50=0.124 μM)[1].

  • CAS Number: 185298-58-2
  • MF: C21H21N3O4
  • MW: 379.41
  • Catalog: Phospholipase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 709.0±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 382.6±35.7 °C

TROLEANDOMYCIN

Troleandomycin (Triacetyloleandomycin), a macrolide acrolide antibiotic, is a selective CYP3A inhibitor. Troleandomycin is an oral corticosteroid for asthma study[1][2][3].

  • CAS Number: 2751-09-9
  • MF: C41H67NO15
  • MW: 813.96800
  • Catalog: Cytochrome P450
  • Density: 1.19g/cm3
  • Boiling Point: 812.5ºC at 760mmHg
  • Melting Point: 170 °C (lit.)
  • Flash Point: 445.2ºC

YTX-465

YTX-465 (YTX465) is a specific small molecule that rescues yeast from a-Syn cytotoxicity with EC50 of 15 nM, via inhibiting Ole1, the yeast homolog of human stearoyl-CoA desaturase (SCD); YTX-465 is inactive at SCD1.

  • CAS Number: 2225824-53-1
  • MF: C25H26N6O3
  • MW: 458.522
  • Catalog: Stearoyl-CoA Desaturase (SCD)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Idraparinux sodium

Idraparinux (sodium) is a polymethylated synthetic pentasaccharide known to interact with the antithrombin III and act as anticoagulant.

  • CAS Number: 149920-56-9
  • MF: C38H55Na9O49S7
  • MW: 1727.177
  • Catalog: Thrombin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pregnenolone 16α-carbonitrile

Pregnenolone 16α-carbonitrile is an orally active prototypical and effective rodent-PXR activator. Pregnenolone 16α-carbonitrile, a synthetic steroid, induces cytochrome P4503A expression. Pregnenolone 16α-carbonitrile exhibits increased resistance to subsequent stressful insults[1][2][3].

  • CAS Number: 1434-54-4
  • MF: C22H31NO2
  • MW: 341.487
  • Catalog: Cytochrome P450
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 508.5±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 261.3±30.1 °C

Acetazolamide D3

Acetazolamide D3 is deuterium labeled Acetazolamide, which is a potent carbonic anhydrase (CA) inhibitor.

  • CAS Number: 1189904-01-5
  • MF: C4H3D3N4O3S2
  • MW: 225.26400
  • Catalog: Carbonic Anhydrase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Methazolamide

Methazolamide is a carbonic anhydrase inhibitor used to treat glaucoma.Target: Carbonic AnhydraseMethazolamide is a carbonic anhydrase inhibitor with Ki of 50 nM, 14 nM and 36 nM for hCA I, hCA II and bCA IV isoforms, respectively [1]. Methazolamide is of strength equal to acetazolamide, another carbonic anhydrase inhibitor used to treat irregular breathing disorders. However, methazolamide differs from acetazolamide in that it fails to activate Ca2+-dependent potassium channels in skeletal muscles. Methazolamide does not impair respiratory work performance in anesthetized rabbits [2]. Oral administration of methazolamide decreases IOPs and AHFRs in clinically normal dogs, with effectiveness diminishing in the evening [3].

  • CAS Number: 554-57-4
  • MF: C5H8N4O3S2
  • MW: 236.272
  • Catalog: Carbonic Anhydrase
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: 402.0±28.0 °C at 760 mmHg
  • Melting Point: 208ºC (dec.)
  • Flash Point: 196.9±24.0 °C

Z-Arg-Arg-pNA

Z-Arg-Arg-pNA is a substrate for cathepsin B and can be used to detect this enzyme activity[1].

  • CAS Number: 122630-71-1
  • MF: C26H36N10O6
  • MW: 584.63
  • Catalog: Cathepsin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Avanafil dibenzenesulfonate

Avanafil (TA-1790) dibenzenesulfonate is a potent and selective phosphodiesterase-5 (PDE-5) inhibitor with IC50 values of 5.2 nM, 630 nM, 5700 nM, 6200 nM, 12000 nM, 27000 nM, 51000 nM and 53000 nM for PDE-5, PDE-6, PDE-4, PDE-10, PDE-8, PDE-7, PDE-2 and PDE-1, respectively. Avanafil dibenzenesulfonate activates NO/cGMP/PKG signaling-pathway to decrease loss in BMD, bone atrophy, and oxidative stress. Avanafil dibenzenesulfonate inhibits cyclic guanosine monophosphate (cGMP) hydrolysis and thus increases cGMP levels. Avanafil dibenzenesulfonate can be used for the research of erectile dysfunction and osteoporosis[1][2][3].

  • CAS Number: 330784-48-0
  • MF: C35H38ClN7O9S2
  • MW: 800.30
  • Catalog: NO Synthase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ACC1/2-IN-2

ACC1/2-IN-1 (compound 4s) is a potent ACC1/2 inhibitor with IC50 values of 98.06 and 29.43 nM for ACC1 and ACC2, respectively. ACC1/2-IN-1 can be used for cancer research[1].

  • CAS Number: 1031411-94-5
  • MF: C24H25N3O3
  • MW: 403.47
  • Catalog: Acetyl-CoA Carboxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S,R)-WT IDH1 Inhibitor 2

(S,R)-WT IDH1 Inhibitor 2 (GSK321) is a potent, selective mutant IDH1 inhibitor with IC50 values of 2.9, 3.8, 4.6 and 46 nM for R132G, R132C, R132H and WT IDH1, respectively, and >100-fold selectivity over IDH2. (S,R)-WT IDH1 Inhibitor 2 induces decrease in intracellular 2-HG, abrogation of the myeloid differentiation block and induction of granulocytic differentiation at the level of leukemic blasts and more immature stem-like cells. (S,R)-WT IDH1 Inhibitor 2 can be used for research of acute myeloid leukemia (AML) and other cancers[1].

  • CAS Number: 1816272-18-0
  • MF: C28H28FN5O3
  • MW: 501.55
  • Catalog: Isocitrate Dehydrogenase (IDH)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PAZ-417

Aleplasinin is an orally active, potent, BBB-penetrated and selectiveSERPINE1 (PAI-1, Plasminogen activator inhibitor-1) inhibitor. Aleplasinin increases amyloid-β (Aβ) catabolism and ameliorates amyloid-related pathology. Aleplasinin improves memory deficiency. Aleplasinin can be used for Alzheimer's disease research[1][2].

  • CAS Number: 481629-87-2
  • MF: C28H27NO3
  • MW: 425.51900
  • Catalog: PAI-1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Kushenol A

Kushenol A is isolated from the root of Sophora flavescent, a non-competitive tyrosinase inhibitor with IC50 and Ki values of 1.1 μM and 0.4 μM, respectively[1].Kushenol A is a flavonoid antioxidant, has inhibitory effects on alpha-glucosidase and beta-amylase[2].Kushenol A is confirmed as potential inhibitors of enzymes targeted by cosmetics for skin whitening and aging[1].

  • CAS Number: 99217-63-7
  • MF: C25H28O5
  • MW: 408.487
  • Catalog: Tyrosinase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 581.7±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 195.8±23.6 °C

yamogenin

Yamogenin (Neodiosgenin) is a diastereomer of diosgenin. Yamogenin (Neodiosgenin) antagonizes the activation of the liver X receptor (LXR) in luciferase ligand assay. Yamogenin (Neodiosgenin) inhibits triacylglyceride (TG) accumulation through the suppression of gene expression of fatty acid synthesis in HepG2 hepatocytes[1].

  • CAS Number: 512-06-1
  • MF: C27H42O3
  • MW: 414.621
  • Catalog: LXR
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 527.1±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 272.6±30.1 °C

AR-7

AR7 is a retinoic acid receptor α (RARα) antagonist.

  • CAS Number: 80306-38-3
  • MF: C15H12ClNO
  • MW: 257.71500
  • Catalog: RAR/RXR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Baicalein 6-O-glucoside

Baicalein 6-O-glucoside is a glucuronidation metabolite of Baicalein[1].

  • CAS Number: 28279-72-3
  • MF: C21H20O10
  • MW: 432.37800
  • Catalog: Xanthine Oxidase
  • Density: 1.642±0.06 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-4981517

CYP3cide (PF-4981517) is a potent, selective and time-dependent inhibitor of cytochrome P4503A4 (CYP3A4). The IC50 values for Midazolam 1’-hydroxylase activity are 0.03 μM, 17 μM, and 71 μM for CYP3A4, CYP3A5, and CYP3A7, respectively. CYP3cide can be used to distinguish the contributions of CYP3A4 versus CYP3A5 on drug metabolism[1].

  • CAS Number: 1390637-82-7
  • MF: C26H32N8
  • MW: 456.586
  • Catalog: Cytochrome P450
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 630.2±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 334.9±31.5 °C

ATX inhibitor 14

ATX inhibitor 14 (compound 4), a indole-based carbamate derivative, is a potent autotaxin (ATX) inhibitor with an IC50 of 0.41 nM. ATX inhibitor 14 has the potential for fibrosis relevant diseases research[1].

  • CAS Number: 2484811-39-2
  • MF: C26H26Cl2N4O3S
  • MW: 545.48
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CP 73850

Zopolrestat (CP73850) is a potent, orally active aldose reductase (AR) inhibitor with an IC50 of 3.1 nM. Zopolrestat is used for the research of diabetic complications[1].

  • CAS Number: 110703-94-1
  • MF: C19H12F3N3O3S
  • MW: 419.37700
  • Catalog: Aldose Reductase
  • Density: 1.58g/cm3
  • Boiling Point: 598.7ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 315.9ºC

Dafadine-A

Dafadine-A, an analog of dafadine, is a novel inhibitor of DAF-9 cytochrome P450 in the nematode Caenorhabditis elegans; also inhibits the mammalian ortholog of DAF-9(CYP27A1). IC50 value:Target: DAF-9(CYP27A1) inhibitorThe DAF-9 cytochrome P450 is a key regulator of dauer formation, developmental timing and longevity in the nematodeCaenorhabditis elegans. Here we describe the first identified chemical inhibitor of DAF-9 and the first reported small-molecule tool that robustly induces dauer formation in typical culture conditions. This molecule (called dafadine) also inhibits the mammalian ortholog of DAF-9(CYP27A1), suggesting that dafadine can be used to interrogate developmental control and longevity in other animals.

  • CAS Number: 1065506-69-5
  • MF: C23H25N3O3
  • MW: 391.463
  • Catalog: Cytochrome P450
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 600.3±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 316.9±31.5 °C

DPP-4-IN-1

DPP-4-IN-1 (compound d1) is a potent DPP-4 (dipeptidyl peptidase 4) inhibitor, with an IC50of 49 nM. DPP-4-IN-1 is a structurally analogs of Alogliptin (HY-A0023A). DPP-4-IN-1 can be used for diabetes research[1].

  • CAS Number: 2215027-46-4
  • MF: C19H19ClN6
  • MW: 366.85
  • Catalog: Dipeptidyl Peptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Leucylarginylproline

Leucylarginylproline is an angiotensin-converting enzyme (ACE) inhibitor with an IC50 of 0.27μM.

  • CAS Number: 133943-59-6
  • MF: C17H32N6O4
  • MW: 384.47400
  • Catalog: Peptides
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-Amino-8-hydroxyquinoline

5-Amino-8-hydroxyquinoline (5A8HQ), a potential anticancer candidate, has promising proteasome inhibitory activity.

  • CAS Number: 13207-66-4
  • MF: C9H8N2O
  • MW: 160.17300
  • Catalog: Proteasome
  • Density: 1.363g/cm3
  • Boiling Point: 408.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: N/A

Boc-Gln-Ala-Arg-pNA hydrochloride salt

Boc-QAR-pNA is a chromogenic substrate of trypsin. Boc-QAR-pNA can be used to test trypsin activity[1][2].

  • CAS Number: 1926163-47-4
  • MF: C25H39N9O8
  • MW: 593.63
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

6',7'-Dihydroxybergamottin

(R)-6',7'-Dihydroxybergamottin ((R)-6′,7′-DHB) is a competitive inhibitor of human and rat CYP1A1 activity with Kis of 55 μM and 1.72 μM, respectively. (R)-6',7'-Dihydroxybergamottin has the potential for cancer research[1].

  • CAS Number: 264234-05-1
  • MF: C21H24O6
  • MW: 372.412
  • Catalog: Cytochrome P450
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 578.2±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 303.5±30.1 °C

ikshusterol 3-o-glucoside

Ikshusterol 3-O-glucoside is a phytochemical that inhibits PLA2 from snake venoms[1].

  • CAS Number: 112137-81-2
  • MF: C35H60O7
  • MW: 592.85
  • Catalog: Phospholipase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 704.8±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 380.0±32.9 °C

AHR-5333

AHR-5333 is a selective human blood neutrophil 5-lipoxygenase inhibitor. AHR-5333 exhibits potent, long-acting activity in rat and guinea pig in vivo models of immediate hypersensitivity[1].

  • CAS Number: 60284-71-1
  • MF: C30H33F2NO4
  • MW: 509.58400
  • Catalog: 5-Lipoxygenase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Asundexian

Asundexian (BAY 2433334) is an orally active coagulation factor Xia (FXIa) inhibitor. Asundexian binds directly, potently, and reversibly to the active site of FXIa and thereby inhibits its activity. Asundexian inhibits human FXIa in buffer with an IC50 of 1 nM[1].

  • CAS Number: 2064121-65-7
  • MF: C26H21ClF4N6O4
  • MW: 592.93
  • Catalog: Factor Xa
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sevelamer

Sevelamer is a phosphate binding drug used to treat hyperphosphatemia in patients with chronic kidney disease; consists of polyallylamine that is crosslinked with epichlorohydrin.

  • CAS Number: 52757-95-6
  • MF: C20H46N4O
  • MW: 358.61
  • Catalog: FXR
  • Density: N/A
  • Boiling Point: 116.1ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 33.9ºC