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.


Anti-infection >
Arenavirus Bacterial CMV Enterovirus Filovirus Fungal HBV HCV HIV HSV Influenza Virus Parasite Reverse Transcriptase RSV SARS-CoV
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Apoptosis >
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Antifolate APC ATM/ATR Aurora Kinase Casein Kinase CDK Checkpoint Kinase (Chk) CRISPR/Cas9 Deubiquitinase DNA Alkylator/Crosslinker DNA-PK DNA/RNA Synthesis Eukaryotic Initiation Factor (eIF) G-quadruplex Haspin Kinase HDAC HSP IRE1 Kinesin LIM Kinase (LIMK) Microtubule/Tubulin Mps1 Nucleoside Antimetabolite/Analog p97 PAK PARP PERK Polo-like Kinase (PLK) PPAR RAD51 ROCK Sirtuin SRPK Telomerase TOPK Topoisomerase Wee1
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15-PGDH 5 alpha Reductase 5-Lipoxygenase Acetyl-CoA Carboxylase Acyltransferase Adenosine Deaminase Adenosine Kinase Aldehyde Dehydrogenase (ALDH) Aldose Reductase Aminopeptidase Angiotensin-converting Enzyme (ACE) ATGL ATP Citrate Lyase Carbonic Anhydrase Carboxypeptidase Cathepsin CETP COMT Cytochrome P450 Dipeptidyl Peptidase Dopamine β-hydroxylase E1/E2/E3 Enzyme Elastase Enolase FAAH FABP Factor Xa Farnesyl Transferase Fatty Acid Synthase (FAS) FXR Glucokinase GSNOR Gutathione S-transferase HCV Protease Hexokinase HIF/HIF Prolyl-Hydroxylase HIV Integrase HIV Protease HMG-CoA Reductase (HMGCR) HSP Indoleamine 2,3-Dioxygenase (IDO) Isocitrate Dehydrogenase (IDH) Lactate Dehydrogenase LXR MAGL Mineralocorticoid Receptor Mitochondrial Metabolism MMP Nampt NEDD8-activating Enzyme Neprilysin PAI-1 PDHK PGC-1α Phosphatase Phosphodiesterase (PDE) Phospholipase Procollagen C Proteinase Proteasome Pyruvate Kinase RAR/RXR Renin ROR Ser/Thr Protease SGK Stearoyl-CoA Desaturase (SCD) Thrombin Tryptophan Hydroxylase Tyrosinase Xanthine Oxidase
Neuronal Signaling >
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VD/VDR
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Tebufelone

Tebufelone (NE-11740), a nonsteroidal anti-inflammatory drug (NSAID), is a selective dual COX-2/5-lipoxygenase inhibitor. Tebufelone displays potent anti-inflammatory, analgesic and anti-pyretic properties[1][2].

  • CAS Number: 112018-00-5
  • MF: C20H28O2
  • MW: 300.43500
  • Catalog: COX
  • Density: 0.992g/cm3
  • Boiling Point: 383.6ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 163.8ºC

Icariin

Icariin is a flavonol glycoside. Icariin inhibits PDE5 and PDE4 activities with IC50s of 432 nM and 73.50 μM, respectively. Icariin also is a PPARα activator.

  • CAS Number: 489-32-7
  • MF: C33H40O15
  • MW: 676.662
  • Catalog: Autophagy
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 948.5±65.0 °C at 760 mmHg
  • Melting Point: 223-225ºC
  • Flash Point: 300.9±27.8 °C

hDHODH-IN-1

hDHODH-IN-1 is a human dihydroorotate dehydrogenase (hDHODH) inhibitor. hDHODH-IN-1 has anti-inflammatory effect[1].

  • CAS Number: 1173715-42-8
  • MF: C17H14N2O2
  • MW: 278.31
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Phytic acid

Phytic acid is a major phosphorus storage compound of most seeds and cereal grains.

  • CAS Number: 83-86-3
  • MF: C6H18O24P6
  • MW: 660.04
  • Catalog: Xanthine Oxidase
  • Density: 2.4±0.1 g/cm3
  • Boiling Point: 1190.7±75.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 673.9±37.1 °C

Talabostat

Talabostat (PT100, Val-boroPro) is a potent, nonselective and orally available dipeptidyl peptidase IV (DPP-IV) inhibitor with a Ki of 0.18 nM.

  • CAS Number: 149682-77-9
  • MF: C9H19BN2O3
  • MW: 214.070
  • Catalog: Dipeptidyl Peptidase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 421.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 208.7±31.5 °C

(2S,3S)-3-[N-(Quinoxaline-2-carbonyl)-L-asparaginyl]amino-2-hydroxy-4- phenylbutanoyl-L-proline, tert-butylamide

R-87366 is a water-soluble human immunodeficiency virus (HIV) protease inhibitor. R-87366 has potent inhibitory for HIV protease with a Ki value of 11 nM. R-87366 can be used for the research of anti-human immunodeficiency virus (HIV)[1].

  • CAS Number: 144779-91-9
  • MF: C32H39N7O6
  • MW: 617.69500
  • Catalog: HIV Protease
  • Density: 1.311g/cm3
  • Boiling Point: 1055.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 592.1ºC

CL-82198

CL-82198 is a selective inhibitor of MMP-13.In vitro: In the presence of 10 and 20 μM of the specific MMP-13 inhibitor, CL-82198, migration of the LS174 cells was significantly reduced by 55 and 52%, respectively. . CL-82198 binds to the S1' pocket of MMP-13 leading to 89% enzyme inhibition at a concentration of 10 μg/ml. The addition of the specific MMP-13 inhibitor CL-82198 at a concentration of 10 μM resulted in a 45±5.6% reduction in the migration of LS174 cells.

  • CAS Number: 307002-71-7
  • MF: C17H22N2O3
  • MW: 302.37
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: 537.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 278.6ºC

Schizandrin A

Schisandrin A inhibits CYP3A activity with an IC50 of 6.60 μM and Ki of 5.83 μM, respectively.

  • CAS Number: 61281-38-7
  • MF: C24H32O6
  • MW: 416.507
  • Catalog: Autophagy
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 544.2±50.0 °C at 760 mmHg
  • Melting Point: 114 °C
  • Flash Point: 215.6±30.0 °C

Exemestane

Exemestane(FCE 24304) is an aromatase inhibitor, inhibits human placental and rat ovarian aromatase with IC50 of 30 nM and 40 nM, respectively.Target: AromataseApproved: October 2005Exemestane competitively inhibits and time-dependently inactivates of human placental aromatase with Ki of 4.3 nM. Exemestane displaces [3H]DHT from rat prostate androgen receptor with IC50 of 0.9 μM [1]. Exemestane (1 μM) increases alkaline phosphatase activity in hFOB and Saos-2 cells and induces the expression of MYBL2, OSTM1, HOXD11, ADCYAP1R1, and glypican 2 in hFOB cells [2]. Exemestane causes aromatase degradation in a dose-responsive manner in MCF-7aro cells [3].Exemestane increases lumbar spine BMD by 14.0% in OVX rats at dose of 100 mg/kg. Exemestane (100 mg/kg) and 17-hydroexemestane (20 mg/kg) significantly reduces an ovariectomy-induced increase in serum pyridinoline and serum osteocalcin in rats and causes significant reductions of serum cholesterol and low-density lipoprotein cholesterol inOVX rats [4].Exemestane (20 mg/kg/day s.c.) induces 26% complete (CR) and 18% partial (PR) tumor regressions in rats with 7,12-dimethylbenzanthracene (DMBA)-induced mammary tumors [5].

  • CAS Number: 107868-30-4
  • MF: C20H24O2
  • MW: 296.403
  • Catalog: Cytochrome P450
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 453.7±45.0 °C at 760 mmHg
  • Melting Point: 155.13°C
  • Flash Point: 169.0±25.7 °C

Zifaxaban

Zifaxaban is a novel, potent, selective, direct and oral factor Xa inhibitor with IC50 of 11.1 nM (human FXa), displays > 10,000-fold selectivity than other serine proteases; also deoes not impair platelet aggregation induced by collagen, adenosine diphosphate (ADP) or arachidonic acid; significantly prolongs clotting time, prothrombin time (PT), and activated partial thromboplastin time (APTT) in the plasma of humans, rabbits, and rats, with a relatively weak effect on thrombin time; strongly suppresses thrombus formation with ED50 values of 3.09 mg/kg in venous thrombosis models in rats.

  • CAS Number: 1378266-98-8
  • MF: C20H16ClN3O4S
  • MW: 429.877
  • Catalog: Factor Xa
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 680.2±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 365.2±31.5 °C

Diacylglycerol acyltransferase inhibitor-1

Diacylglycerol acyltransferase inhibitor-1 is a diacylglycerol acyltransferase (DGAT1) inhibitor.

  • CAS Number: 1610800-25-3
  • MF: C21H23N5O2
  • MW: 377.44
  • Catalog: Acyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Glucocorticoid receptor-IN-2

Glucocorticoid receptor-IN-2 (Compound WX019) is a selective glucocorticoid receptor (GR) modulator with anti-inflammatory effect. Glucocorticoid receptor-IN-2 exhibits very good transcriptional repressive activity with an IC50 of 0.171 nM against hMMP1, and comparable transcriptional activation activity with an EC50 of 0.94 nM against MMTV[1].

  • CAS Number: 2664932-65-2
  • MF: C25H20F4N6O2
  • MW: 512.46
  • Catalog: Glucocorticoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MMP-9/MMP-13 INHIBITOR I

MMP-9/MMP-13 Inhibitor I is a potent MMP-9 and MMP-13 inhibitor with IC50s of both 0.9 nM. MMP-9/MMP-13 Inhibitor I shows >20-folds selectivity for MMP-9/MMP-13 over other MMPs[1].

  • CAS Number: 204140-01-2
  • MF: C25H25N3O6S
  • MW: 495.55
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Captopril disulfide

Captopril disulfide is a metabolite of Captopril with antihypertensive activity[1].

  • CAS Number: 64806-05-9
  • MF: C18H28N2O6S2
  • MW: 432.55500
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: 1.383g/cm3
  • Boiling Point: 714.796ºC at 760 mmHg
  • Melting Point: 224-226ºC
  • Flash Point: 386.095ºC

PCSK9-IN-18

PCSK9-IN-18 (compound 188) is a potent PCSK9 inhibitor with a KD value of <200 nM[1].

  • CAS Number: 2455425-15-5
  • MF: C15H20N6O2S
  • MW: 348.42
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BMS-654457

BMS-654457 is a small-molecule, reversible inhibitor of factor XIa (FXIa), binding with human and rabbit FXIa with Kis of 0.2 and 0.42 nM, respectively.

  • CAS Number: 1004551-41-0
  • MF: C36H37N5O4
  • MW: 603.71
  • Catalog: Factor Xa
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Suc-Val-Pro-Phe-pNA

Suc-Val-Pro-Phe-pNA is a substrate for cathepsin G and can be used to detect the activity of this enzyme[1].

  • CAS Number: 95192-11-3
  • MF: C29H35N5O8
  • MW: 581.61700
  • Catalog: Cathepsin
  • Density: 1.337±0.06 g/cm3 (20 °C, 760 mmHg)
  • Boiling Point: 971.6±65.0 °C (760 mmHg)
  • Melting Point: N/A
  • Flash Point: N/A

SHIP2-IN-1

SHIP2-IN-1 is a potent SHIP2 inhibitor, inhibits SHIP2 activity, with an IC50 of 2 µM. SHIP2-IN-1 blocks GSK3β activation by phosphorylation at the Ser9 residue. SHIP2-IN-1 is used in the research of Alzheimer’s disease[1].

  • CAS Number: 2252247-80-4
  • MF: C17H13Cl2FN4O
  • MW: 379.22
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Baicalein

Baicalein (5,6,7-Trihydroxyflavone) is a xanthine oxidase inhibitor with an IC50 value of 3.12 mM.

  • CAS Number: 491-67-8
  • MF: C15H10O5
  • MW: 270.237
  • Catalog: Xanthine Oxidase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 575.9±50.0 °C at 760 mmHg
  • Melting Point: 256-271 °C(lit.)
  • Flash Point: 225.3±23.6 °C

PAT-048

PAT-048 is a potent, selective and orally active autotaxin inhibitor, inhibits IL-6 mRNA expression, but shows no effect on autotaxin protein and pulmonary lysophosphatidic acid (LPA) production in lung fibrosis model. PAT-048 shows an IC50 and IC90 of 20 nM and 200 nM for autotaxin in mouse plasma. PAT-048 reduces dermal fibrosis in vivo[1][2].

  • CAS Number: 1359983-15-5
  • MF: C22H18ClF2N3O2S
  • MW: 461.91
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Curzerene

Curzerene is a sesquiterpene is isolated from the rhizome of Curculigo orchioides Gaertn with anti-cancer activity. Curzerene inhibits glutathione S-transferase A1 (GSTA1) mRNA and protein expression. Curzerene induces cell apoptosis[1].

  • CAS Number: 17910-09-7
  • MF: C15H20O
  • MW: 216.319
  • Catalog: Gutathione S-transferase
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 282.8±40.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 117.5±14.2 °C

DCN1-UBC12-IN-3

DCN1-UBC12-IN-3 is potent and selective DCN1-UBC12 inhibitor with an IC50 of 2.25 nM. Anticardiac fibrotic effect[1].

  • CAS Number: 2374827-45-7
  • MF: C30H30N8O3S2
  • MW: 614.74
  • Catalog: E1/E2/E3 Enzyme
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

P32/98

P32/98 hemifumarateis a potent inhibitor of dipeptidyl peptidase IV with a Ki value of 130 nM. P32/98 hemifumarate improves glucose tolerance, insulin sensitivity and β-cell responsiveness in fatty Zucker rat model[1][2][3].

  • CAS Number: 251572-86-8
  • MF: C22H40N4O6S2
  • MW: 520.706
  • Catalog: Dipeptidyl Peptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BN82002

BN82002 is a synthetic inhibitor of CDC25 phophatases, with IC50s of 2.4-6.3 μM for recombinant CDC25 phosphatases.

  • CAS Number: 396073-89-5
  • MF: C19H25N3O4
  • MW: 359.42000
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HIV Protease Substrate I

HIV Protease Substrate I is a chromogenic substrate of HIV-1 protease. HIV Protease Substrate I has the cleavage site of HIV protease[1].

  • CAS Number: 124077-63-0
  • MF: C47H74N14O15
  • MW: 1075.18
  • Catalog: HIV Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Trelagliptin succinate

Trelagliptin(SYR-472) is a long acting dipeptidyl peptidase-4 (DPP-4) inhibitor that is being developed for the treatment of type 2 diabetes (T2D). IC50 value:Target: DPP4Two Phase II clinical studies have been completed with Efficacy and Safety of SYR-472 in Subjects With Type 2 Diabetes Mellitus. Phase III clinical studies with trelagliptin in Japan to evaluate its safety and efficacy in a once-weekly oral treatment regimen. Currently, all available DPP-4 inhibitors are dosed once-daily. A once-weekly treatment, such as trelagliptin, would provide patients with a convenient treatment alternative and has the potential to improve treatment compliance.

  • CAS Number: 1029877-94-8
  • MF: C22H26FN5O6
  • MW: 475.470
  • Catalog: Dipeptidyl Peptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Febuxostat

Febuxostat(TEI 6720;TMX 67 ) is selective xanthine oxidase inhibitor with Ki of 0.6 nM.IC50 value: 0.6 nM (Ki) [1]Target: xanthine oxidasein vitro: Febuxostat displays potent mixed-type inhibition of the activity of purified bovine milk xanthine oxidase, with Ki and Ki' values of 0.6 nM and 3.1 nM respectively, indicating inhibition of both the oxidized and reduced forms of xanthine oxidase [1]. in vivo: Febuxostat (5–6 mg/kg/day) combined with fructose significantly lowers blood pressure, UA, triglycerides, and insulin in rats compared with fructose alone. Febuxostat (5–6 mg/kg/day) combined with fructose also reduces glomerular pressure, renal vasoconstriction, and afferent arteriolar area in rats compared with fructose alone [2]. Febuxostat prevents hyperuricemia in 5/6 nephrectomy (5/6 Nx)+oxonic acid (OA)+Febuxostat(Fx) rats and ameliorates proteinuria, preserves renal function and prevents glomerular hypertension in both 5/6 nephrectomy (5/6 Nx)+vehicle (V)+Febuxostat(Fx) and 5/6 nephrectomy (5/6 Nx)+oxonic acid (OA)+Febuxostat(Fx) groups [3]. Febuxostat (5 mg/kg/d by gavage for 8 days) treatment after transverse aortic constriction (TAC) attenuates the TAC-induced left ventricular (LV) hypertrophy and dysfunction. Febuxostat blunts the TAC-induced increases in nitrotyrosine (indicating reduced myocardial oxidative stress), p-Erk(Thr202/Tyr204), and p-mTOR(Ser2488), with no effect on total Erk or total mTOR [4].

  • CAS Number: 144060-53-7
  • MF: C16H16N2O3S
  • MW: 316.375
  • Catalog: Xanthine Oxidase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 536.6±60.0 °C at 760 mmHg
  • Melting Point: 238-239ºC
  • Flash Point: 278.3±32.9 °C

KP-457

KP-457 is a selective a disintegrin and metalloproteinase 17 (ADAM17) inhibitor, with higher selectivity for ADAM17 than for other MMPs and ADAM10, and 5050s are 11.1 nM (ADAM17), 748 nM (ADAM10), 717 nM (MMP2), 9760 nM (MMP3), 2200 nM (MMP8), 5410 nM (MMP9), 930 nM (MMP13), 2140 nM (MMP14), and 7100 nM (MMP17), respectively.

  • CAS Number: 1365803-52-6
  • MF: C21H24N2O7S2
  • MW: 480.55
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Z-Asp-Glu-Val-Asp-chloromethylketone

Z-DEVD-CMK is an irreversible inhibitor of most of the cathepsins in vitro[1].

  • CAS Number: 250584-13-5
  • MF: C27H35ClN4O12
  • MW: 643.04
  • Catalog: Cathepsin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JNJ 0966

JNJ0966 is a highly selective MMP-9 zymogen inhibitor with an IC50 of 440 nM.

  • CAS Number: 315705-75-0
  • MF: C16H16N4O2S2
  • MW: 360.45
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A