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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2-Ketoglutaric acid-d4

2-Ketoglutaric acid-d4 is the deuterium labeled 2-Ketoglutaric acid[1]. 2-Ketoglutaric acid (Alpha-Ketoglutaric acid) is an intermediate in the production of ATP or GTP in the Krebs cycle. 2-Ketoglutaric acid also acts as the major carbon skeleton for nitrogen-assimilatory reactions. 2-Ketoglutaric acid is a reversible inhibitor of tyrosinase (IC50=15 mM)[2].

  • CAS Number: 1381759-60-9
  • MF: C5H2D4O5
  • MW: 150.12
  • Catalog: Tyrosinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AGN 194310

AGN 194310(VTP-194310) is a potent and selective pan-RARs agonist with Kd values of 3/2/5 nM for RARα/β/γ respectively.IC50 value: 3/2/5 nM (Kd for RARα/β/γ) [1][2]Target: RARs agonistin vitro: A high affinity pan-RAR antagonist (AGN194310, K(d) for binding to RARs = 2-5 nM) inhibited colony formation (by 50%) by all three lines at 16-34 nM, and led to a transient accumulation of flask-cultured cells in G1 followed by apoptosis. AGN194310 is 12-22 fold more potent than all-trans retinoic acid (ATRA) against cell lines and also more potent in inhibiting the growth of primary prostate carcinoma cells [2].in vivo: The administration of all-trans retinoic acid to VAD mice resulted in a transient reduction in NF-kappaB activity and, conversely, a single dose of the RAR-pan-antagonist, AGN 194310, administered to control mice, led to a marked, transient induction of whole-body luminescence [3]. Mice were treated with AGN194310, a synthetic retinoid that antagonises the physiological function of the three RAR isotypes (alpha, beta, gamma) but does not interact with RXRs. Analyses of the granulocytic lineage using Gr-1, c-Kit and CD11b antibodies, demonstrated that granulocyte numbers were strikingly increased across haemopoietic compartments in all AGN194310-treated mice. A significant increase in the frequency of progenitor cells containing granulocytes was observed in the bone marrow of mice following treatment with AGN194310 [4].

  • CAS Number: 229961-45-9
  • MF: C28H24O2S
  • MW: 424.554
  • Catalog: RAR/RXR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 598.1±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 315.5±30.1 °C

L-690,488

L-690488 is a prodrug of L-690330 and is a selective inositol monophosphatase (IMPase) inhibitor. L-690488 has more effective cell penetration than L-690330[1][2].

  • CAS Number: 142523-14-6
  • MF: C32H52O16P2
  • MW: 754.69300
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L 601920-0

L 601920-0 is a ROR gamma modulator extracted from patent US20110263046 A1, in figure 2.

  • CAS Number: 20231-57-6
  • MF: C25H40O3
  • MW: 388.58300
  • Catalog: ROR
  • Density: 1.07g/cm3
  • Boiling Point: 484ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 183.1ºC

TAT-cyclo-CLLFVY TFA

TAT-cyclo-CLLFVY is a selective HIF-1 dimerization inhibitor. TAT-cyclo-CLLFVY blocks protein-protein interaction of recombinant HIF-1α, but not HIF-2α, with HIF-1β (IC50=1.3 μM). TAT-cyclo-CLLFVY inhibits hypoxia-induced HIF-1 activity, and decreases VEGF and CAIX expression in osteosarcoma and breast cancer cells in vitro. TAT-cyclo-CLLFVY also reduces tubularization of hypoxic HUVECs.

  • CAS Number: 1446322-66-2
  • MF: C116H176N32O33
  • MW: 2546.86
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Giripladib

Giripladib (PLA-695) is a indole-based inhibitor of cytosolic phospholipase A2 (cPLA2). Giripladib can be used for osteoarthritis and breast cancer research[1][2].

  • CAS Number: 865200-20-0
  • MF: C41H36ClF3N2O4S
  • MW: 745.25
  • Catalog: Phospholipase
  • Density: 1.29g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ayanin

Ayanin is a bioflavonoid isolated from Croton schiedeanus Schlecht. Ayanin is a non-selective phosphodiesterase1-4 inhibitor and can be used for the study of respiratory disease,such as allergic asthma et al[1].

  • CAS Number: 572-32-7
  • MF: C18H16O7
  • MW: 344.315
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 600.8±55.0 °C at 760 mmHg
  • Melting Point: 173℃
  • Flash Point: 221.5±25.0 °C

palmostalin B

Palmostatin B is an Acyl protein thioesterase 1 and 2 (APT-1, APT-2) inhibitor. Palmostatin B reduces cell viability in a panel of NRAS mutant melanoma cell lines. Palmostatin B inhibits Ras depalmitoylation in cells[1][2].

  • CAS Number: 1233365-12-2
  • MF: C23H36O4
  • MW: 376.53
  • Catalog: Phospholipase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Antihistamine-1

Antihistamine-1 is a H1-antihistamine (Ki=6.9 nM) with acceptable blood-brain barrier penetration and also an inhibitor of CYP2D6 and hERG channel with IC50s of 5.4 and 0.8 μM, respectively.

  • CAS Number: 1186430-60-3
  • MF: C23H24FN5
  • MW: 389.47
  • Catalog: Histamine Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Acetildenafil

Acetildenafil is a derivative of the phosphodiesterase 5 (PDE5) inhibitor Sildenafil.

  • CAS Number: 831217-01-7
  • MF: C25H34N6O3
  • MW: 466.576
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 131-133ºC
  • Flash Point: N/A

SSI-4

SSI-4 is an inhibitor of Stearoyl CoA desaturase 1 (SCD1) , which can be modified with 11C, used as a ligand to in vivo small animal PET/CT imaging of SCD1[1].

  • CAS Number: 1875084-68-6
  • MF: C19H21ClN4O3
  • MW: 388.85
  • Catalog: Stearoyl-CoA Desaturase (SCD)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Milrinone-d3

Milrinone-d3 is deuterium labeled Milrinone. Milrinone is a PDE3 inhibitor, and also an inotrope and vasodilator.

  • CAS Number: 2749393-50-6
  • MF: C12H6D3N3O
  • MW: 214.24
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dehydrojuncusol

Dehydrojuncusol, a potent HCV inhibitor, targets HCV NS5A and is able to inhibit RNA replication of replicons harboring resistance mutations to anti-NS5A direct-acting antivirals. Dehydrojuncusol significantly inhibits HCV infection when added after virus inoculation of HCV genotype 2a (EC50=1.35 µM)[1].

  • CAS Number: 117824-04-1
  • MF: C18H16O2
  • MW: 264.31800
  • Catalog: HCV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MCH-1 antagonist 1

MCH-1 antagonist 1 is a potent melanin concentrating hormone (MCH-1) antagonist with a Ki of 2.6 nM. MCH-1 antagonist 1 also inhibits CYP3A4 with an IC50 of 10 μM.

  • CAS Number: 1039825-68-7
  • MF: C25H26N4O2
  • MW: 414.50000
  • Catalog: MCHR1 (GPR24)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ALLM

ALLM (Calpain inhibitor II) is a potent inhibitor of calpain and cathepsin proteases. ALLM inhibits neuronal cell death and improves chronic neurological function after spinal cord injury (SCI)[1][2].

  • CAS Number: 110115-07-6
  • MF: C19H35N3O4S
  • MW: 401.564
  • Catalog: Cathepsin
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 676.5±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 362.9±31.5 °C

TFLLRNPNDK-NH2

TFLLRNPNDK-NH2 is a biological active peptide. (This peptide is a thrombin receptor activating peptide. This PAR-1 agonist peptide reversibly binds to PAR-1 mimicking the 'tethered ligand' that thrombin makes available through proteolytic cleavage of substrate. It is also known to cause increase in liquid and protein permeability much like thrombin.)

  • CAS Number: 145229-90-9
  • MF: C54H89N17O15
  • MW: 1216.39
  • Catalog: Thrombin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK2981278

GSK2981278 is a retinoid-related orphan receptor gamma (RORy) modulator, extracted from patent WO/2015061515 A1, example 124.

  • CAS Number: 1474110-21-8
  • MF: C25H35NO5S
  • MW: 461.614
  • Catalog: ROR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 622.6±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 330.3±34.3 °C

Nagilactone B

Nagilactone B, extracted from the root bark of Podocarpus nagi, is a liver X receptor (LXR) agonist.

  • CAS Number: 19891-51-1
  • MF: C19H24O7
  • MW: 364.390
  • Catalog: LXR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 644.6±55.0 °C at 760 mmHg
  • Melting Point: 258-261℃
  • Flash Point: 233.7±25.0 °C

AC 261066

AC-261066 is a potent, orally available and isoform-selective retinoic acid beta2 (RARbeta2) receptor agonist, with a pEC50 of 8.0[1].

  • CAS Number: 870773-76-5
  • MF: C17H20FNO4S
  • MW: 353.40800
  • Catalog: RAR/RXR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Palmitic acid-d2

Palmitic acid-d2 is the deuterium labeled Palmitic acid. Palmitic acid is a long-chain saturated fatty acid commonly found in both animals and plants. Palmitic acid can induce the expression of glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in in mouse granulosa cells[1][2].

  • CAS Number: 62689-96-7
  • MF: C16H30D2O2
  • MW: 258.436
  • Catalog: HSP
  • Density: 0.9±0.1 g/cm3
  • Boiling Point: 340.6±5.0 °C at 760 mmHg
  • Melting Point: 61-62.5ºC(lit.)
  • Flash Point: 154.1±12.5 °C

1-(4-Hydroxy-2-Methoxyphenyl)-3-(4-hydroxy-3-prenylphenyl)propane

1-(4-Hydroxy-2-methoxyphenyl)-3-(4-hydroxy-3-prenylphenyl), isolated from Broussonetia kazinoki, shows in vitro inhibition of protein tyrosine phosphatase 1B (PTP1B) with an IC50 of 13.00 μM. PTP1B is a negative regulator of insulin action and an important mediator in the pathogenesis of insulinresistance and non-insulin dependent diabetes mellitus. PTP1B is regarded as a significant target for type 2 diabetes[1].

  • CAS Number: 376362-03-7
  • MF: C21H26O3
  • MW: 326.429
  • Catalog: Phosphatase
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 490.3±40.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 250.3±27.3 °C

1,4-DPCA ethyl ester

1,4-DPCA ethyl ester is the ethyl ester of 1,4-DPCA and can inhibit factor inhibiting HIF (FIH)[1].

  • CAS Number: 86443-19-8
  • MF: C15H12N2O3
  • MW: 268.26700
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KT185

KT185 is an orally-bioavailable, brain-penetrant and selective ABHD6 inhibitor, with an IC50 0.21 nM in Neuro2A cells[1].

  • CAS Number: 1472640-86-0
  • MF: C32H33N5O2
  • MW: 519.64
  • Catalog: MAGL
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nicodicosapent

Nicodicosapent is a fatty acid niacin conjugate that is also an inhibitor of the sterol regulatory element binding protein (SREBP), a key regulator of cholesterol metabolism proteins such as PCSK9, HMG-CoA reductase, ATP citrate lyase, and NPC1L1.

  • CAS Number: 1269181-69-2
  • MF: C28H39N3O2
  • MW: 449.628
  • Catalog: HMG-CoA Reductase (HMGCR)
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 677.5±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 363.5±31.5 °C

Isocryptotanshinone

Isocryptotanshinone is a potent signal transducer and activator of transcription 3 (STAT3) and protein tyrosine phosphatase 1B PTP1B inhibitor, with an IC50 of 56.1 μM for PTP1B.

  • CAS Number: 22550-15-8
  • MF: C19H20O3
  • MW: 296.36000
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CVT 10216

CVT-10216 is a highly selective, reversible aldehyde dehydrogenase-2 (ALDH-2) inhibitor with an IC50 of 29 nM. CVT-10216 also has inhibitory effect of ALDH-1 with an IC50 of 1.3 μM. CVT-10216 can reduces excessive alcohol drinking in alcohol-preferring rats and exhibits anxiolytic effects[1].

  • CAS Number: 1005334-57-5
  • MF: C24H19NO7S
  • MW: 465.475
  • Catalog: Aldehyde Dehydrogenase (ALDH)
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 714.2±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 385.8±35.7 °C

PCPA methyl ester hydrochloride

PCPA methyl ester hydrochloride (4-Chloro-DL-phenylalanine methyl ester hydrochloride), a reversible tryptophan hydroxylase inhibitor, is a serotonin (5-HT) synthesis inhibitor. PCPA methyl ester hydrochloride crosses the blood brain barrier and reduces 5-HT central availability[1][2].

  • CAS Number: 14173-40-1
  • MF: C10H13Cl2NO2
  • MW: 250.122
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: 296.3ºC at 760 mmHg
  • Melting Point: 186-189 °C(lit.)
  • Flash Point: 133ºC

HSP70/SIRT2-IN-2

HSP70/SIRT2-IN-2 (Compounds 1a) is a dual inhibitor for SIRT2 and HSP70, with IC50 of 45.1±5.0 μM for SIRT2. HSP70/SIRT2-IN-2 has antitumor activity[1].

  • CAS Number: 1796557-72-6
  • MF: C17H13N3S3
  • MW: 355.50
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

7-Ethoxyresorufin-d5

7-Ethoxyresorufin-d5 is deuterium labeled 7-Ethoxyresorufin. 7-Ethoxyresorufin (Resorufin ethyl ether) is a fluorometric substrate and competitive inhibitor of cytochrome P450, especially CYP1A1. 7-Ethoxyresorufin also inhibits NO synthase[1][2].

  • CAS Number: 2749329-28-8
  • MF: C14H6D5NO3
  • MW: 246.27
  • Catalog: NO Synthase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

7-[(1,4,5,6-Tetrahydro-4-methyl-6-oxopyridazin)-3-yl]-4H-1,4-benzoxazin-3(2H)-one

Bemoradan (compound 10a) is an orally active and selective canine Phosphodiesterase (PDE) fraction III inhibitor. Bemoradan is a long-acting, potent, inotropic vasodilator and a novel cardiotonic agent, and can be used in congestive heart failure research[1].

  • CAS Number: 112018-01-6
  • MF: C13H13N3O3
  • MW: 259.26
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A