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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XZ426

XZ426 is a potent integrase strand transfer inhibitor with anti- HIV activity[1].

  • CAS Number: 1638504-52-5
  • MF: C22H24F2N4O4
  • MW: 446.45
  • Catalog: HIV Integrase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Proteasome Substrate II

Z-Leu-Leu-Glu-AMC is a substrate peptide, and can be used for determination of postacidic-like hydrolysing activity of 20S proteasome[1]

  • CAS Number: 348086-66-8
  • MF: C35H44N4O9
  • MW: 664.745
  • Catalog: Proteasome
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 967.8±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 539.1±34.3 °C

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

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

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

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

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

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

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

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

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

CD 2314

CD2314 is a potent and selective RARβ receptor agonist with a Kd of 195 nM in S91 melanoma cells[1].

  • CAS Number: 170355-37-0
  • MF: C23H24O2S
  • MW: 364.50000
  • Catalog: RAR/RXR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Doxycycline

Doxycycline monohydrate is an antibiotic and broad-spectrum metalloproteinase (MMP) inhibitor[1][2][3][4].

  • CAS Number: 17086-28-1
  • MF: C22H26N2O9
  • MW: 462.450
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: 819.4ºC at 760 mmHg
  • Melting Point: 167-168℃
  • Flash Point: 449.4ºC

LHVS

LHVS is a potent, non-selective cysteine protease inhibitor[1]. LHVS effectively blocks T. gondii microneme protein secretion (IC50=10 μM), gliding motility, and cell invasion[2].

  • CAS Number: 170111-28-1
  • MF: C28H37N3O5S
  • MW: 527.68
  • Catalog: Parasite
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hsp90-IN-17

Hsp90-IN-17 (Example 5) is an HSP90 inhibitor that can be used in the study of proliferative diseases, such as cancer and neurodegenerative diseases[1].

  • CAS Number: 1253584-78-9
  • MF: C21H20N4O7
  • MW: 440.41
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BR1

PRL-3 Inhibitor I is a potent PRL-3 inhibitor with an IC50 of 0.9 μM. PRL-3 Inhibitor I shows a reduced invasion in cell-based assay[1].

  • CAS Number: 893449-38-2
  • MF: C17H11Br2NO2S2
  • MW: 485.21300
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FK706

FK706 is a potent, slow-binding and competitive inhibitor of human neutrophil elastase with an IC50 of 83 nM and a Ki of 4.2 nM. FK706 also inhibits mouse neutrophil elastase and porcine pancreatic elastase with IC50s of 22 nM and 100 nM, respectively, and has no inhibitory activity against other serine proteinases such as human pancreatic trypsin, human pancreatic α-chymotrypsin and human leukocyte cathepsin G. FK706 has anti-inflammatory effect[1][2].

  • CAS Number: 144055-55-0
  • MF: C26H32F3N4NaO7
  • MW: 592.54
  • Catalog: Elastase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RORγt modulator 3

RORγt modulator 3 (Compound 23) is a modulator of retinoid-related orphan receptor γt (RORγt). RORγt modulator 3 can be used for the research of RORyt mediated diseases such as, e.g., pain, inflammation, COPD, asthma, rheumatoid arthritis, colitis, multiple sclerosis, psoriasis, neurodegenerative diseases and cancer[1].

  • CAS Number: 2230877-38-8
  • MF: C25H25ClFN3O4S
  • MW: 518.00
  • Catalog: ROR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Elvitegravir(GS-9137,JTK-303)

Elvitegravir is an HIV integrase inhibitor for HIV-1IIIB, HIV-2EHO and HIV-2ROD with IC50 of 0.7 nM, 2.8 nM and 1.4 nM, respectively.

  • CAS Number: 697761-98-1
  • MF: C23H23ClFNO5
  • MW: 447.884
  • Catalog: HIV
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 623.6±55.0 °C at 760 mmHg
  • Melting Point: 93-96°C
  • Flash Point: 330.9±31.5 °C

Deserpidine

Deserpidine (Harmonyl) is an alkaloid isolated from the root of Rauwolfia canescens related to Reserpine. Deserpidine is used as an antihypertensive agent and a tranquilizer. Deserpidine is a competitive angiotensin converting enzyme (ACE) inhibitor. Deserpidine also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex[1][2][3].

  • CAS Number: 131-01-1
  • MF: C32H38N2O8
  • MW: 578.653
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 676.1±55.0 °C at 760 mmHg
  • Melting Point: ~275 °C (dec.)(lit.)
  • Flash Point: 362.7±31.5 °C

Leptosin D

Leptosin D, a thiodiketopiperazine alkaloid, is a mushroom tyrosinase inhibitor, with an IC50 of 28.4 μM[1].

  • CAS Number: 159518-77-1
  • MF: C25H24N4O3S2
  • MW: 492.61
  • Catalog: Tyrosinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

6,7-Dihydroxycoumarin-4-acetic Acid

6,7-Dihydroxy-4-coumarinylacetic acid is a potent and selective inhibitor of ALR2. 6,7-Dihydroxy-4-coumarinylacetic acid inhibits ALR2, SDH andALR1 with IC50s of 9.6, 288 and 66.3 μM, respectively. 6,7-Dihydroxy-4-coumarinylacetic acid clearly suppresses galactitol accumulation[1].

  • CAS Number: 88404-14-2
  • MF: C11H8O6
  • MW: 236.17800
  • Catalog: Aldose Reductase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 230ºC
  • Flash Point: N/A

AA-861

Docebenone (AA 861) is a potent, selective and orally active 5-LO (5-lipoxygenase) inhibitor.

  • CAS Number: 80809-81-0
  • MF: C21H26O3
  • MW: 326.42900
  • Catalog: 5-Lipoxygenase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SR1001

SR1001 is a selective RORα and RORγ inverse agonist; inhibits TH17 cell differentiation and function.

  • CAS Number: 1335106-03-0
  • MF: C15H13F6N3O4S2
  • MW: 477.402
  • Catalog: ROR
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nanterinone

Nanterinone (UK 61260) is a positive inotropic and arterial vasodilating agent. Nanterinone is a phosphodiesterase inhibitor[1].

  • CAS Number: 102791-47-9
  • MF: C15H15N3O
  • MW: 253.29900
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.24g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A