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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1-Galloyl-beta-glucose

β-Glucogallin is a potent and selective aldose reductase (AKR1B1) inhibitor. β-Glucogallin can be isolated from the medicinal plant Emblica officinalis[1].

  • CAS Number: 13405-60-2
  • MF: C13H16O10
  • MW: 332.26000
  • Catalog: Aldose Reductase
  • Density: 1.85
  • Boiling Point: N/A
  • Melting Point: 214℃
  • Flash Point: N/A

7-Hydroxycoumarinyl arachidonate

7-Hydroxycoumarinyl arachidonate (7-HCA) is a fluorogenic substrate of cytosolic phospholipase A2 (PLA2). 7-Hydroxycoumarinyl arachidonate is also a fluorogenic substrate for monoacylglycerol lipase (MAGL). MAGL protein catalyzes the hydrolysis of 7-Hydroxycoumarinyl arachidonat to generate Arachidonic acid (AA) and the highly fluorescent 7-hydroxyl coumarin (7-HC; HY-N0573). Release of 7-HC can be measured using a fluorometer[1][2][3].

  • CAS Number: 161180-11-6
  • MF: C29H36O4
  • MW: 448.594
  • Catalog: MAGL
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 584.7±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 289.4±28.5 °C

(S,R,S)-AHPC-C5-COOH

(S,R,S)-AHPC-C5-COOH (VH032-C5-COOH) is a synthesized E3 ligase ligand-linker conjugate, contains the VH032 VHL-based ligand and a linker to form PROTACs. VH-032 is a selective and potent inhibitor of VHL/HIF-1α interaction with a Kd of 185 nM, has the potential for the study of anemia and ischemic diseases[1].

  • CAS Number: 2267282-19-7
  • MF: C29H42N4O5S
  • MW: 558.73
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-ethylmaleimide

N-Ethylmaleimide (NEM) is a cysteine protease inhibitor[1]. N-ethylmaleimide specific inhibits phosphate transport in mitochondria[2].

  • CAS Number: 128-53-0
  • MF: C6H7NO2
  • MW: 125.13
  • Catalog: Cathepsin
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 210.0±9.0 °C at 760 mmHg
  • Melting Point: 43-46 °C(lit.)
  • Flash Point: 73.3±0.0 °C

Floramanoside C

Floramanoside C shows 2,2-diphenyl-1-picrylhydrazyl scavenging and aldose reductase inhibitory activities[1].

  • CAS Number: 1403981-95-2
  • MF: C21H18O15
  • MW: 510.36
  • Catalog: Aldose Reductase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BMS-986242

BMS-986242 is an orally active, potent and selective indoleamine-2,3-dioxygenase 1 (IDO1) inhibitor. BMS-986242 can be used for the research of cancer[1].

  • CAS Number: 1923844-48-7
  • MF: C24H24ClFN2O
  • MW: 410.91
  • Catalog: Indoleamine 2,3-Dioxygenase (IDO)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(R)-Mephenytoin

(R)-Mephenytoin ((-)-Mephenytoin), the R-enantiomer of Mephenytoin. Mephenytoin is an Anticonvulsant agent[1][2].

  • CAS Number: 71140-51-7
  • MF: C12H14N2O2
  • MW: 218.25200
  • Catalog: Cytochrome P450
  • Density: 1.154g/cm3
  • Boiling Point: N/A
  • Melting Point: 137-138ºC
  • Flash Point: N/A

HIF-1/2α-IN-2

HIF-1/2α-IN-2 is an inhibitor of HIF-1/2α. HIF-1/2α-IN-2 decrease HIF-1/2α levels and induces iron starvation response by targeting Iron Sulfur Cluster Assembly 2 (ISCA2)[1].

  • CAS Number: 862974-22-9
  • MF: C16H11FN4O2S
  • MW: 342.35
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NSC45586 free base

NSC45586 free base (NCS 45586, NCI45586) is a potent, specific PHLPP2 inhibitor with IC50 of 4 uM, targets the PHLPP2 PP2C domain, suppresses MYC and triggers cell death.

  • CAS Number: 739301-85-0
  • MF: C20H18N6O3
  • MW: 390.403
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-O-Methyl Tolcapone

3-O-Methyltolcapone (Ro 40-7591) is a metabolite of Tolcapone. Tolcapone is an orally active, reversible, selective and potent COMT inhibitor. Tolcapone crosses the blood-brain barrier, and can be used for treatment of Parkinson's disease[1][2].

  • CAS Number: 134612-80-9
  • MF: C15H13NO5
  • MW: 315.32100
  • Catalog: COMT
  • Density: 1.317g/cm3
  • Boiling Point: 474.8ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 240.9ºC

Dapaconazole

Dapaconazole, as an antifungal agent, inhibits sterol 14α-demethylase cytochrome P450 activity with an IC50 of 1.4 μM[1].

  • CAS Number: 1269726-67-1
  • MF: C19H15Cl2F3N2O
  • MW: 415.236
  • Catalog: Cytochrome P450
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 512.8±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 263.9±30.1 °C

Antitumor agent-88

Antitumor agent-88 exhibits potent antimitotic activity and arrests cell in the G2/M phase. Antitumor agent-88 disrupts the microtubule and the cytoskeleton in CYP1A1-expressing breast cancer cells. Antitumor agent-88 is also a competitive inhibitor of CYP1A1 (Ki: 1.4 μM)[1].

  • CAS Number: 1422527-87-4
  • MF: C23H30N2O7S
  • MW: 478.56
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY 2955303

LY2955303 is a potent and selective retinoic acid receptor gamma (RARγ) antagonist with a Ki of 1.09 nM.

  • CAS Number: 1433497-19-8
  • MF: C36H42N4O3
  • MW: 578.74
  • Catalog: RAR/RXR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KZR-616

KZR-616 (KZR616) is a potent, selective dual immunoproteasome subunit LMP7/LMP2 inhibitor with IC50 of 39 nM/139 nM, weakly inhibits β5, MECL-1 and no acitivty against β1 subunit; shows no inhibition at 10 uM against a broad selectivity panel of 20 serine, metallo-, cysteine and aspartyl proteases and 11 hydrolases; demonstrates efficacy in the anti-collagen antibody induced arthritis (CAIA) models. Other Indication Phase 2 Clinical

  • CAS Number: 1629677-75-3
  • MF: C30H42N4O8
  • MW: 586.686
  • Catalog: Proteasome
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-MPPA

2-MPPA (GPI-5693) is an orally active and selective glutamate carboxypeptidase II (GCP II; PSMA) inhibitor with an IC50 of 90 nM[1][2].

  • CAS Number: 254737-29-6
  • MF: C8H14O4S
  • MW: 206.25900
  • Catalog: Carboxypeptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Boceprevir

Boceprevir is a novel, potent, highly selective, orally bioavailable HCV NS3 protease inhibitor with Ki of 14 nM in both enzyme assay and EC90 of 350 nM in cell-based replicon assay.

  • CAS Number: 394730-60-0
  • MF: C27H45N5O5
  • MW: 519.677
  • Catalog: HCV
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ONO-RS-082

ONO-RS-082 is an inhibitor of phospholipase A (PLA)[1]. ONO-RS-082 inhibits PLA2 with the IC50 of 1.0 μM, but does not inhibit PLC even at 100 μM[2].

  • CAS Number: 99754-06-0
  • MF: C21H22ClNO3
  • MW: 371.85700
  • Catalog: Phospholipase
  • Density: 1.247g/cm3
  • Boiling Point: 580.5ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 304.9ºC

Temocapril

Temocapril is an orally active angiotensin-converting enzyme (ACE) inhibitor. Temocapril can be used for the research of hypertension, congestive heart failure, acute myocardial infarction, insulin resistance, and renal diseases[1][2].

  • CAS Number: 111902-57-9
  • MF: C23H28N2O5S2
  • MW: 476.60900
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: 1.33 g/cm3
  • Boiling Point: 717.4ºC at 760 mmHg
  • Melting Point: >230ºC (dec)
  • Flash Point: 387.7ºC

PDK4-IN-1 hydrochloride

PDK4-IN-1 hydrochloride is an anthraquinone derivative and a potent and orally active pyruvate dehydrogenase kinase 4 (PDK4) inhibitor with an IC50 value of 84 nM. PDK4-IN-1 hydrochloride potently represses cellular transformation and cellular proliferation and induces apoptosis. PDK4-IN-1 hydrochloride has antidiabetic, anticancer and anti-allergic activity[1].

  • CAS Number: 2310262-11-2
  • MF: C22H20ClN3O2
  • MW: 393.87
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IDH-C227

IDH-C227 is a potent and selective IDH1R132H inhibitor. IDH-C227 has anticancer effcts[1].

  • CAS Number: 1355324-14-9
  • MF: C30H31FN4O2
  • MW: 498.59100
  • Catalog: Isocitrate Dehydrogenase (IDH)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Canrenone

Canrenone (Aldadiene; SC9376; SC14266) is an aldosterone antagonist extensively used as a diuretic agent.

  • CAS Number: 976-71-6
  • MF: C22H28O3
  • MW: 340.456
  • Catalog: Mineralocorticoid Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 541.1±50.0 °C at 760 mmHg
  • Melting Point: 158-160ºC
  • Flash Point: 237.6±30.2 °C

2-Deoxy-D-glucose-d1

2-Deoxy-D-glucose-d1 is the deuterium labeled 2-Deoxy-D-glucose. 2-Deoxy-D-glucose is a glucose analog that acts as a competitive inhibitor of glucose metabolism, inhibiting glycolysis via its actions on hexokinase[1][2].

  • CAS Number: 188004-07-1
  • MF: C6H11DO5
  • MW: 165.16
  • Catalog: HSV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

licoricidin

Licoricidin (LCD) is isolated from Glycyrrhiza uralensis Fisch, possesses anti-cancer activities.Licoricidin (LCD) inhibit SW480 cells (IC50=7.2 μM) by inducing cycle arrest, apoptosis and autophagy, and is a potential chemopreventive or chemotherapeutic agent against colorectal cancer[1].Licoricidin (LCD) inhibits Lung Metastasis by inhibition of tumor angiogenesis and lymphangiogenesis as well as changes in the local microenvironment of tumor tissues the anticarcinogenic effect[1].licoricidin enhanced gemcitabine-induced cytotoxicity in Osteosarcoma (OS) cells by inactivation of the Akt and NF-κB pathways in vitro and in vivo[3]. Licoricidin blocks UVA-induced photoaging via ROS scavenging, limits the activity of MMP-1, it can be considered as an active ingredient in new topically applied anti-ageing formulations[4].

  • CAS Number: 30508-27-1
  • MF: C26H32O5
  • MW: 424.529
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 610.8±55.0 °C at 760 mmHg
  • Melting Point: 161.0-162.5℃
  • Flash Point: 323.2±31.5 °C

2-Amino-1,3-octadecanediol

D-Erythro-dihydrosphingosin directly inhibits cytosolic phospholipase A2α (cPLA2α) activity.

  • CAS Number: 764-22-7
  • MF: C18H39NO2
  • MW: 301.508
  • Catalog: Phospholipase
  • Density: 0.9±0.1 g/cm3
  • Boiling Point: 446.2±25.0 °C at 760 mmHg
  • Melting Point: 70-72ºC
  • Flash Point: 223.7±23.2 °C

GCPII-IN-1

GCPII-IN-1 is a glutamate carboxypeptidase II (GCPII, or PSMA) inhibitor scaffold with a Ki of 44.3 nM[1].

  • CAS Number: 1025796-32-0
  • MF: C12H21N3O7
  • MW: 319.31
  • Catalog: Carboxypeptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VX-222 (VCH-222, Lomibuvir)

VX-222 (VCH-222) is a novel, potent and selective inhibitor of HCV polymerase with IC50 of 0.94-1.2 μM, 15.3-fold less effective for mutant M423T, and 108-fold less effective for mutant I482L.IC50 Value: 0.94 μM (HCV NS5B 1a); 1.2 μM (HCV NS5B 1b)Target: HCVVX-222 is a small molecule non-nucleoside inhibitor of HCV NS5B polymerase that is being investigated for the treatment of hepatitis C virus infection. VX-222 exhibits non-competitive and selective inhibition in HCV NS5B of genotype 1a and 1b, with IC50 of 0.94 and 1.2 μM, respectively. VX-222 selectively inhibits the replication of subgenomic HCV genotype 1a and 1b with an EC50 of 22.3 and 11.2 nM, respectively. [1] Similarly, a recent study shows that VX-222 inhibits the 1b/Con1 HCV subgenomic replicon, with an EC50 of 5 nM. In rats and dogs, VCH-222 displays fine pharmacokinetic pro le, including low total body clearance and excellent oral bioavailability (greater than 30%) and good ADME properties. VCH-222 is biotransformed by several enzymes (CYP1A1, 2A6, 2B6, 2C8, CYP 3A4, UGT1A3) and is predicted to be actively transported in liver and excreted mainly intact in bile or as glucuronide adducts.

  • CAS Number: 1026785-59-0
  • MF: C25H35NO4S
  • MW: 445.615
  • Catalog: HCV
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 640.5±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 341.2±31.5 °C

T-5224

T-5224 is a selective inhibitor of c-Fos/activator protein (AP)-1. It also inhibits MMP3/13 with IC50s of 10 nM.

  • CAS Number: 530141-72-1
  • MF: C29H27NO8
  • MW: 517.527
  • Catalog: MMP
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 774.1±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 422.0±32.9 °C

L-778,123

L-778123 is an inhibitor of FPTase and GGPTase-I with IC50 of 2 nM and 98 nM in enzyme inhibition determination.IC50 value: 2 nM [1]Target: FPTasein vitro: L-778123 can completely inhibit Ki-Ras prenylation. [1] L-778123 as a farnesyltransferase inhibitor can have a good cytotoxic activity as a classic anti-cancer agent. [2]in vivo: In the dog model, L-778123 inhibits HDJ2 prenylation and produces measurable, albeit slight (5%), levels of unprenylatedRap1A in PBMCs. [1]

  • CAS Number: 183499-57-2
  • MF: C22H20ClN5O
  • MW: 405.88
  • Catalog: Farnesyl Transferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PD 132002

PD 132002 is an orally active, potent renin inhibitor. PD 132002 weakly inhibits pepsin. PD 132002 produces substantial reductions in blood pressure[1].

  • CAS Number: 134452-04-3
  • MF: C31H50N4O9S
  • MW: 654.81500
  • Catalog: Renin
  • Density: 1.28g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Deltarasin

Deltarasin is an inhibitor of KRAS-PDEδ interaction with Kd of 38 nM for binding to purified PDEδ.

  • CAS Number: 1440898-61-2
  • MF: C40H37N5O
  • MW: 603.755
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 824.3±75.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 452.3±37.1 °C