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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Topiroxostat-d4

Topiroxostat-d4 is deuterium labeled Topiroxostat. Topiroxostat (FYX-051) is a potent and orally active xanthine oxidoreductase (XOR) inhibitor with an IC50 value of 5.3 nM and a Ki value of 5.7 nM. Topiroxostat exhibits weak CYP3A4-inhibitory activity (18.6%). Topiroxostat has the potential for hyperuricemia treatment[1][2].

  • CAS Number: 2732868-49-2
  • MF: C13H4D4N6
  • MW: 252.27
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bradykinin potentiator B

Bradykinin potentiator B (Bradykinin potentiating peptide B) is venom of Agkistrodon halys blomhoffi. Bradykinin potentiator B is a potent ACE inhibitor. Bradykinin potentiator inhibits the activity of bradykinin inhibitory peptidase[1].

  • CAS Number: 30892-86-5
  • MF: C56H91N15O13
  • MW: 1182.41000
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: 1.48g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ritonavir-d6

Ritonavir-d6 (ABT 538-d6) is the deuterium labeled Ritonavir. Ritonavir (ABT 538) is an inhibitor of HIV protease used to treat HIV infection and AIDS. Ritonavir is also a SARS-CoV 3CLpro inhibitor with an IC50 of 1.61 μM[1][2].

  • CAS Number: 1217720-20-1
  • MF: C37H42D6N6O5S2
  • MW: 726.98
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DL-AP3

DL-AP3 is a competitive mGluR1 and mGluR5 antagonist. DL-AP3 is also an inhibitor of phosphoserine phosphatase. DL-AP3 has neuroprotective effect[1][2][3].

  • CAS Number: 5652-28-8
  • MF: C3H8NO5P
  • MW: 169.073
  • Catalog: mGluR
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: 481.6±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 245.1±31.5 °C

Nafamostat mesylate

Nafamostat mesylate, a synthetic serine protease inhibitor, is an anticoagulant.Target: Serine ProteaseTranilast (FUT-175) is an antiallergic drug for bronchial asthma. It has been used for the treatment of allergic disorders such as asthma, allergic rhinitis and atopic dermatitis. It has also been investigated for use as an antiproliferative drug on drug-eluting stents.A 20-40 mg/h dose of FUT-175 prolonged coagulation time sufficiently in the instrumental blood of the extracorporeal circuit but not in the systemic blood. Its anticoagulant activity decreased immediately after hemodialysis. Therefore, we could manage all patients without any bleeding trouble during hemodialysis with FUT-175 as an anticoagulant. Although there were side effects of FUT-175, such as nausea, vomiting, itching and eruption, they were not serious, and FUT-175 could be administered without interruption. FUT-175 seems to be useful as an anticoagulant during hemodialysis for patients susceptible to bleeding.

  • CAS Number: 82956-11-4
  • MF: C21H25N5O8S2
  • MW: 539.58
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: 637.2ºCat 760 mmHg
  • Melting Point: 259-261°C
  • Flash Point: 339.1ºC

Cyclosporin A-d3

Cyclosporin A-d3 is the d3-labeled Cyclosporin A (HY-B0579)[1].

  • CAS Number: 222295-76-3
  • MF: C62H108D3N11O12
  • MW: 1205.63
  • Catalog: Complement System
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Filibuvir

Filibuvir is a potent, selective non-nucleoside inhibitor (NNI) of the HCV nonstructural 5B protein (NS5B) RNA-dependent RNA polymerase, and it binds noncovalently in the “Thumb 2” pocket of NS5B. In vitro, filibuvir is equipotent against genotype 1a and 1b replicons, with an EC50 of 59 nM[1].

  • CAS Number: 877130-28-4
  • MF: C29H37N5O3
  • MW: 503.63600
  • Catalog: HCV Protease
  • Density: 1.29g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HIV-1 integrase inhibitor 3

HIV-1 integrase inhibitor 3 is a HIV-1 integrase strand transfer (INST) inhibitor with an IC50 of 2.7 nM.

  • CAS Number: 1638504-56-9
  • MF: C21H22F2N4O4
  • MW: 432.42
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Z-LLF-CHO

Z-LLF-CHO (Z-Leu-Leu-Phe-CHO) is a potent inhibitor of the chymotrypsin-like activity of the pituitary multicatalytic proteinase complex (Ki = 460 nM). Z-LLF-CHO is also a NF-κB nuclear translocation inhibitor[1][2].

  • CAS Number: 133429-58-0
  • MF: C29H39N3O5
  • MW: 509.64
  • Catalog: Proteasome
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ezatiostat

Ezatiostat is a glutathione analog inhibitor of glutathione S-transferase P1-1 (GSTP1-1).

  • CAS Number: 168682-53-9
  • MF: C27H35N3O6S
  • MW: 529.648
  • Catalog: Gutathione S-transferase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 749.7±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 407.2±32.9 °C

MK-0822

L-873724 is a potent, orally bioavailable, selective and reversible[2] non-basic cathepsin K inhibitor, with IC50s of 0.2, 178, 264, and 5239 nM for cathepsin K, cathepsin S, cathepsin L, cathepsin B, respectively[1]. L-873724 also exhibits an IC50 of 0.5 nM for rabbit cathepsin K. L-873724 inhibits bone resorption[2].

  • CAS Number: 603139-12-4
  • MF: C23H26F3N3O3S
  • MW: 481.53100
  • Catalog: Cathepsin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bexarotene

Bexarotene is a selective retinoid X receptors (RXR) agonist for the treatment of cutaneous T-cell lymphoma.

  • CAS Number: 153559-49-0
  • MF: C24H28O2
  • MW: 348.478
  • Catalog: Autophagy
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 489.7±44.0 °C at 760 mmHg
  • Melting Point: 230-231ºC
  • Flash Point: 229.5±23.1 °C

RORγt modulator 2

RORγt modulator 2 (Compound 21) is a modulator of retinoid-related orphan receptor γt (RORγt) with the IC50 of <50 nM. RORγt modulator 2 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: 2247083-47-0
  • MF: C28H29ClN2O4S
  • MW: 525.06
  • Catalog: ROR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

YM 976

YM976 is a phosphodiesterase 4 (PDE4) inhibitor with an IC50 of 2.2 nM. YM976 shows the dissociation of anti-inflammatory activities from emetic effects and inhibits the antigen-induced airway responses[1].

  • CAS Number: 191219-80-4
  • MF: C17H16ClN3O
  • MW: 313.78100
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.27g/cm3
  • Boiling Point: 485.4ºC at 760mmHg
  • Melting Point: 132.7-134.0ºC(lit.)
  • Flash Point: 247.4ºC

phosphoramidon

Phosphoramidon, a microbial metabolite, is a specific metalloprotease thermolysin inhibitor with an IC50 of 0.4 μg/mL. Phosphoramidon also inhibits endothelin-converting enzyme (ECE), neutral endopeptidase (NEP), and angiotensin-converting enzyme (ACE) with IC50 values of 3.5, 0.034, and 78 μM, respectively[1][2][3].

  • CAS Number: 36357-77-4
  • MF: C23H34N3O10P
  • MW: 543.50400
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: 1.48 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DPP-IV-IN-1

DPP-IV-IN-1 is a potent inhibitor of dipeptidyl peptidase IV (DPP-IV), a highly specific serine protease, with an IC50 of 4.6 nM.

  • CAS Number: 625110-37-4
  • MF: C11H18FN3O2
  • MW: 243.27800
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ML252

ML252 is a selective inhibitor of potassium channel, targeting to KCNQ2 channel (Kv7.2) (IC50=69 nM). ML252 also inhibits Cytochrome P450 with IC50s of 6.1 nM (CYP1A2), 18.9 nM (CYP2C9), 3.9 nM (CYP3A4), 19.9 nM (CYP2D6), respectively[1][2].

  • CAS Number: 1392494-64-2
  • MF: C20H24N2O
  • MW: 308.41700
  • Catalog: Potassium Channel
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SREBP/SCAP-IN-1

SREBP/SCAP-IN-1(compound 10b) is a selectiveSREBP/SCAPinhibitor[1].

  • CAS Number: 2763493-89-4
  • MF: C28H40F2N4O
  • MW: 486.64
  • Catalog: Fatty Acid Synthase (FAS)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

h-NTPDase-IN-2

h-NTPDase-IN-2 (compound 3l) is a pan-inhibitor of h-NTPDase, with IC50s of 0.35 μM (h-NTPDase1), 4.81 μM (h-NTPDase2), 37.73 μM (h-NTPDase3), 10.32 μM (h-NTPDase8), respectively[1].

  • CAS Number: 2939933-03-4
  • MF: C19H16N4S
  • MW: 332.42
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-Desmethyl Sildenafil

N-Desmethyl Sildenafil (Desmethylsildenafil) is a major metabolite of Sildenafil. Sildenafil is a potent phosphodiesterase type 5 (PDE5) inhibitor[1][2].

  • CAS Number: 139755-82-1
  • MF: C21H28N6O4S
  • MW: 460.55
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.44g/cm3
  • Boiling Point: 685.7ºC at 760 mmHg
  • Melting Point: 158-160ºC
  • Flash Point: 368.5ºC

4-nitrocatechol

4-Nitrocatechol is a potent lipoxygenase inhibitor[1].

  • CAS Number: 3316-09-4
  • MF: C6H5NO4
  • MW: 155.108
  • Catalog: 5-Lipoxygenase
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 358.2±32.0 °C at 760 mmHg
  • Melting Point: 173-177 °C(lit.)
  • Flash Point: 168.8±13.6 °C

2-(2-Propyn-1-yl)octanoic acid

2-Hexyl-4-pentynoic acid ((±)-2-Hexyl-4-pentynoic acid), valproic acid (VPA) derivative, exhibits potential roles of HDAC inhibition (IC50=13 µM) and HSP70 induction. Potent neuroprotective effects. 2-Hexyl-4-pentynoic acid causes histone hyperacetylation and protect against glutamate-induced excitotoxicity in cultured neurons[1].

  • CAS Number: 96017-59-3
  • MF: C11H18O2
  • MW: 182.259
  • Catalog: HDAC
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 287.1±23.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 138.7±17.3 °C

Ro 41-5253

Ro 41-5253 is an orally active selective retinoic acid receptor alpha (RARα) antagonist. Ro 41-5253 can bind RARα without inducing transcription or affecting RAR/RXR heterodimerization and DNA binding. Ro 41-5253 can inhibit cancer cell proliferation and induce apoptosis, has antitumor activity[1][2].

  • CAS Number: 144092-31-9
  • MF: C28H36O5S
  • MW: 484.64700
  • Catalog: Apoptosis
  • Density: 1.154g/cm3
  • Boiling Point: 661.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 353.8ºC

MK-0952

MK-0952 is a selective and orally active PDE4 inhibitor, with an IC50 of 0.53 nM. MK-0952 has the potential for Alzheimer’s disease study[1][2].

  • CAS Number: 934995-87-6
  • MF: C28H22FN3O4
  • MW: 483.49000
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ML298

ML298 is a potent, selective phospholipase PLD2 inhibitor with IC50 of 355 nM, displays >53-fold selectivity over PLD1 (IC50>20 uM); decreases invasive migration in U87-MG glioblastoma cells; has an attractive DMPK profile, making it an attractive tool compound to further dissect PLD2 function in multiple cellular and in vivo environments.

  • CAS Number: 1426916-02-0
  • MF: C22H23F3N4O2
  • MW: 432.439
  • Catalog: Phospholipase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 650.5±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 347.2±31.5 °C

A-58365B

A-58365B is an Angiotensin-converting Enzyme (ACE) inhibitor. A-58365B has antihypertensive effects[1].

  • CAS Number: 87896-53-5
  • MF: C13H15NO6
  • MW: 281.26100
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: 1.54g/cm3
  • Boiling Point: 608.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 321.7ºC

JG-258

JG-258 is an inactive negative control for Hsp70 inhibitors[1].

  • CAS Number: 2241517-83-7
  • MF: C20H22ClN3OS3
  • MW: 452.06
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CPDA

CPDA is a novel potent SH2 domain-containing inositol phosphatase 2 (SHIP2) inhibitor that can effectively ameliorate insulin resistance in 3T3-L1 adipocytes.Target: SHIP2in vitro: CPDA was found to enhance insulin signaling.in vivo: CPDA greatly improves abnormal glucose metabolism in diabetic animals. CPDA was also found to improve the abnormal glucose metabolism in db/db mice.

  • CAS Number: 1415834-63-7
  • MF: C20H15ClF2N2O2
  • MW: 388.79500
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PR-924

A potent, specific immunoproteasome LMP7 subunit inhibitor with IC50 of 25 nM, >100-fold selectivity over β5c, β1i, β1c, β2i and β2c subunits (IC50>3 uM); shows weak activity toward LMP2 and no detectable activity toward β1, β2, or MECL1.

  • CAS Number: 1416709-79-9
  • MF: C37H38N4O5
  • MW: 618.721
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 969.0±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 539.8±34.3 °C

[Tyr6]-Angiotensin II

[Tyr6]-Angiotensin II is a peptide fragment , and can bind to the angiotensin converting enzyme 2 [1].

  • CAS Number: 52634-95-4
  • MF: C53H73N11O13
  • MW: 1072.21
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A