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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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
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CA 074 TFA

CA-074 is a potent inhibitor of cathepsin B with a Ki of 2 to 5 nM.

  • CAS Number: 134448-10-5
  • MF: C18H29N3O6
  • MW: 383.43900
  • Catalog: Cathepsin
  • Density: 1.267g/cm3
  • Boiling Point: 728.9ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 394.7ºC

BAY 87-2243

BAY 87-2243 is a highly potent and selective hypoxia-inducible factor-1 (HIF-1) inhibitor.

  • CAS Number: 1227158-85-1
  • MF: C26H26F3N7O2
  • MW: 525.526
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 677.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 363.7±34.3 °C

VT-464

Seviteronel (VT-464) is a potent CYP17 lyase inhibitor(h-Lyase IC50=69 nM) that demonstrated both exceptional in vitro lyase/hydroxylase selectivity (~10-fold) and oral activity in a hamster model of androgen biosynthesis inhibition.

  • CAS Number: 1610537-15-9
  • MF: C18H17F4N3O3
  • MW: 399.340
  • Catalog: Cytochrome P450
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 536.3±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 278.2±28.7 °C

JTE-151

JTE-151 is a RORγ inhibitor, which can suppress overactive immune response through inhibition of RORγ related to the activation of Th17 cells, making JTE-151 possible to be used in autoimmune disease research[1].

  • CAS Number: 1404380-58-0
  • MF: C28H37ClN2O4
  • MW: 501.06
  • Catalog: ROR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dihydrorotenone

Dihydrorotenone, a natural pesticide, is a potent mitochondrial inhibitor. Dihydrorotenone probably induces Parkinsonian syndrome. Dihydrorotenone induces human plasma cell apoptosis by triggering endoplasmic reticulum stress and activating p38 signaling pathway[1].

  • CAS Number: 6659-45-6
  • MF: C23H24O6
  • MW: 396.433
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 553.9±50.0 °C at 760 mmHg
  • Melting Point: 216 °C
  • Flash Point: 241.6±30.2 °C

Bemfivastatin hemicalcium

Bemfivastatin (PPD 10558) hemicalcium is an orally active lipid-lowering agent and HMG-CoA reductase inhibitor. Bemfivastatin hemicalcium enhances the activity of liver extracts. Bemfivastatin hemicalcium has no-observed adverse effect levels (NOAEL) with dosages of ≥320 mg/kg/d (rat developmental toxicity), ≥12.5 mg/kg/d (rabbit maternal toxicity), ≥25 mg/kg/d (rabbit developmental toxicity), respectively. Bemfivastatin hemicalcium can be used in the study of statin-related hypercholesterolemic myalgia in statin-intolerant patients.

  • CAS Number: 805241-64-9
  • MF: C34H37FN2O6.1/2Ca
  • MW: 607.74
  • Catalog: HMG-CoA Reductase (HMGCR)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cbl-b-IN-9

Cbl-b-IN-9 (Compound 300) is a casitas B-lineage lymphoma-b (Cbl-b) and c-Cbl inhibitor with IC50s of 5.6 nM and 4.7 nM, respectively[1].

  • CAS Number: 2815223-41-5
  • MF: C30H33F3N6O2
  • MW: 566.62
  • Catalog: E1/E2/E3 Enzyme
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sildenafil Mesylate

Sildenafil Mesylate is an orally active and selective phosphodiesterase type 5 (PDE5) inhibitor. Sildenafil Mesylate can be used in studies of erectile dysfunction and cancer[1].

  • CAS Number: 1308285-21-3
  • MF: C23H34N6O7S2
  • MW: 570.68
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TK05

TK05 is a potent and selective inhibitor of leukotriene C4 synthase (LTC4S) with an IC50 of 95 nM[1].

  • CAS Number: 1245734-61-5
  • MF: C31H25ClN2O5
  • MW: 540.99
  • Catalog: Gutathione S-transferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Monomyristin

1-Monomyristin, extracted from Serenoa repens, inhibits the hydrolysis of 2-oleoylglycerol (IC50=32 μM) and fatty acid amide hydrolase (FAAH) activity (IC50=18 μM). 1-Monomyristin shows antibacterial activity against Staphylococcus aureus and Aggregatibacter actinomycetemcomitans and also antifungal activity against Candida albicans[1][2][3].

  • CAS Number: 589-68-4
  • MF: C17H34O4
  • MW: 302.449
  • Catalog: Bacterial
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 424.8±25.0 °C at 760 mmHg
  • Melting Point: 68-70ºC
  • Flash Point: 141.3±16.7 °C

OBAA

(2E)-OBAA is a potent phospholipase A2 (PLA2) inhibitor, with an IC50 of 70 nM. (2E)-OBAA induces apoptosis of HUVEC cells. (2E)-OBAA blocks Melittin-induced Ca2+ influx in Trypanosoma brucei, with an IC50 of 0.4 μM[1][2][3][4].

  • CAS Number: 221632-26-4
  • MF: C28H44O3
  • MW: 428.647
  • Catalog: Apoptosis
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 558.6±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 305.7±26.6 °C

Rovunaptabin

Rovunaptabin (ARC 183) is a DNA aptamer, which is a single-stranded DNA molecule consisting of 15 deoxynucleotides that forms well-defined three-dimensional configuration, allowing it to bind to thrombin with high affinity and specificity.

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LU-002i

LU-002i is a subunit-selective human proteasome β2c and β2i inhibitor with an IC50 value of 220 nM for β2i[1].

  • CAS Number: 1838705-22-8
  • MF: C35H52N4O7
  • MW: 640.81
  • Catalog: Proteasome
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Varespladib sodium

Varespladib sodium (LY315920 sodium) is a potent and selective group IIA, secretory phospholipase A2 (sPLA2) inhibitor with an IC50 of 9 nM. Varespladib sodium exhibits the significant inhibitory effect on sPLA2 activity in serum from various species including rat, rabbit, guinea pig and human with IC50s of 8.1 nM, 5.0 nM, 3.2 nM and 6.2 nM, respectively[1].

  • CAS Number: 172733-42-5
  • MF: C21H19N2NaO5
  • MW: 402.37600
  • Catalog: Phospholipase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ginsenoside F1

Ginsenoside F1, an enzymatically modified derivative of Ginsenoside Rg1, demonstrates competitive inhibition of CYP3A4 activity and weaker inhibition of CYP2D6 activity.

  • CAS Number: 53963-43-2
  • MF: C36H62O9
  • MW: 638.872
  • Catalog: Cytochrome P450
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 751.7±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 408.4±32.9 °C

Trifolirhizin

Trifolirhizin is a pterocarpan flavonoid isolated from the roots of Sophora flavescens. Trifolirhizin possesses potent tyrosinase inhibitory activity with an IC50 of 506 μM[1]. Trifolirhizin exhibits potential anti-inflammatory and anticancer activities[2].

  • CAS Number: 6807-83-6
  • MF: C22H22O10
  • MW: 446.404
  • Catalog: Tyrosinase
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 658.7±55.0 °C at 760 mmHg
  • Melting Point: 142-144ºC
  • Flash Point: 352.2±31.5 °C

ONO 4817

ONO-4817 is a potent inhibitor of matrix metalloproteinase (MMP). Inhibition of matrix metalloproteinases (MMPs) is expected to suppress atherosclerotic neointimal proliferation and thus limits atheromatous plaque progression. ONO-4817 suppresses the development of aortic intimal hyperplasia in experimental hyperlipidemic rabbit[1].

  • CAS Number: 223472-31-9
  • MF: C22H28N2O6
  • MW: 416.46800
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

h15-LOX-2 inhibitor 1

h15-LOX-2 inhibitor 1 (Comp 105) is a human epithelial 15-lipoxygenase-2 (h15-LOX-2) inhibitor with IC50 of 0.34 μM[1].

  • CAS Number: 478040-08-3
  • MF: C17H13F3N2S
  • MW: 334.36
  • Catalog: 5-Lipoxygenase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Deltarasin

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

  • CAS Number: 1440898-82-7
  • MF: C40H38ClN5O
  • MW: 640.216
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ML299

ML299 is a potent, CNS penetrant, dual phospholipase PLD1/PLD2 probe with IC50 of 6 nM/20 nM, respectively; robustly increases caspase 3/7 activation under serum-free conditions, provides a dose-dependent decrease (100 nM to 10 uM) in invasive migration in U87-MG cells, with statistical significance reached at both the 1 uM and 10 uM doses.

  • CAS Number: 1426916-00-8
  • MF: C23H26BrFN4O2
  • MW: 489.380
  • Catalog: Phospholipase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 708.8±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 382.5±32.9 °C

Alicapistat

Alicapistat (ABT-957) is an orally active selective inhibitor of human calpains 1 and 2 for the potential use in the treatment of Alzheimer's disease (AD).

  • CAS Number: 1254698-46-8
  • MF: C25H27N3O4
  • MW: 433.50
  • Catalog: Proteasome
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(1S,2S)-Bortezomib

(1S,2S)-Bortezomib is an enantiomer of Bortezomib. Bortezomib is a cell-permeable, reversible, and selective proteasome inhibitor, and potently inhibits 20S proteasome (Ki of 0.6 nM) by targeting a threonine residue. Bortezomib disrupts the cell cycle, induces apoptosis, and inhibits NF-κB. Bortezomib is an anti-cancer agent and the first therapeutic proteasome inhibitor to be used in humans[1][2][3].

  • CAS Number: 1132709-14-8
  • MF: C19H25BN4O4
  • MW: 384.237
  • Catalog: Proteasome
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fluvastatin

Fluvastatin (Leschol) inhibits HMG-CoA reductase activity with IC50 of 8 nM.IC50 value: 8 nMTarget: HMG-CoA reductaseFluvastatin is a competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase (HMGCR), the enzyme that catalyzes the conversion of HMG-CoA to mevalonic acid, the rate-limiting step in cholesterol biosynthesis. Human hepatocellular carcinoma cell (HCC) studies indicate that Fluvastatin induces G2/M phase arrest. In the presence of Fluvastatin, HCC cells show a decrease of Bcl-2 and procaspase-9 expression, and an increase in Bax, cleaved caspase-3, and cytochrome c. Fluvastatin is antilipemic and is used to reduce plasma cholesterol levels and prevent cardiovascular disease.

  • CAS Number: 93957-54-1
  • MF: C24H26FNO4
  • MW: 411.466
  • Catalog: HMG-CoA Reductase (HMGCR)
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 681.8±55.0 °C at 760 mmHg
  • Melting Point: 194-197ºC
  • Flash Point: 366.1±31.5 °C

CM 10

CM10 is a potent and selective aldehyde dehydrogenase 1A family inhibitor (ALDH1Ai), with IC50s of 1700, 740, and 640 nM for ALDH1A1, ALDH1A2, and ALDH1A3, respectively. CM10 does not inhibit any of the other ALDH family members. CM10 can regulate metabolism and has anti-cancer activity[1].

  • CAS Number: 692269-09-3
  • MF: C20H23N3O
  • MW: 321.42
  • Catalog: Aldehyde Dehydrogenase (ALDH)
  • Density: 1.12±0.1 g/cm3(Predicted)
  • Boiling Point: 512.4±52.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

3-Methyl-2-butenoic acid [8-hydroxymethyl-1,5-dimethyl-5-(4-methyl-3-pentenyl)-12-oxabicyclo[9.1.0]dodeca-3,7-dien-2-yl] ester

Vibsanin A, a protein kinase C (PKC) activator, exhibits anti-proliferative activity against human cancer cell lines. Vibsanin A is also a HSP90 inhibitor[1].

  • CAS Number: 72506-14-0
  • MF: C25H38O4
  • MW: 402.57
  • Catalog: HSP
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 501.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 158.5±23.6 °C

Frovocimab

Frovocimab (LY 3015014) is a humanized IgG4 monoclonal antibody (mAb) that neutralizes PCSK9. Frovocimab inhibits PCSK9 binding to LDL receptor (LDLR) while permitting the normal proteolytic cleavage of the bound intact PCSK9[1].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rosuvastatin D3 Sodium

Rosuvastatin D3 Sodium is deuterium labeled Rosuvastatin, which is a competitive inhibitor of HMG-CoA reductase with IC50 of 11 nM.

  • CAS Number: 1279031-70-7
  • MF: C22H24D3FN3NaO6S
  • MW: 506.53800
  • Catalog: HMG-CoA Reductase (HMGCR)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: >76°C (分解)
  • Flash Point: N/A

Ganodermanondiol

Ganodermanondiol is a melanogenesis inhibitor isolated from the Ganoderma lucidum[1].Ganodermanondiol exhibits potent cytoprotective effects on tert-butyl hydroperoxide-induced hepatotoxicity[2]. Ganodermanondiol shows significant anti-HIV-1 protease activity with an IC50 of 90 μM[3]. Ganodermanondiol exhibits a strong anticomplement activity against the classical pathway of the complement system with an IC50 of 41.7μM[4].

  • CAS Number: 107900-76-5
  • MF: C30H48O3
  • MW: 456.700
  • Catalog: HIV Protease
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 580.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 318.9±26.6 °C

Brinzolamide

Brinzolamide(AL 4862) is a potent carbonic anhydrase II inhibitor with IC50 of 3.19 nM.Target: carbonic anhydrase IIBrinzolamide (< 1 mg) ophthalmic suspension lowers intraocular pressure in Dutch-belted pigmented rabbits in a dose-dependent manner with an onset within 0.5 hour and a peak response by 1-2 hours. Brinzolamide (0.6 mg) ophthalmic suspension lowers intraocular pressure in laser-treated glaucomatous cynomolgus monkeys in a dose-dependent manner with an onset within 1 hour and a peak response by 3 hours. Brinzolamide dosages of 30 mg/kg, produces a 44% reduction in intestinal charcoal meal progression, but 1 and 10 mg/kg produced 8% and 18% decreases, respectively, in male CD-1 mice. Brinzolamide of 1 mg/kg, 10 mg/kg, and 30 mg/kg prolongs barbiturate sleep time by 57%, 15%, and 35%, respectively, in male CD-1 mice [1]. Brinzolamide (< 3%) produces significantly greater mean percent intraocular pressure reductions and mean intraocular pressure reductions compared with placebo in patients with primary, open-angle glaucoma or ocular hypertension. The optimal intraocular pressure-lowering concentration of brinzolamide is 1%, brinzolamide 1% is well tolerated by patients with primary open-angle glaucoma or ocular hypertension when administered twice daily [2].

  • CAS Number: 138890-62-7
  • MF: C12H21N3O5S3
  • MW: 383.507
  • Catalog: Carbonic Anhydrase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 586.0±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 308.2±32.9 °C

BI8626

BI8626 is a specific inhibitor of the ubiquitin ligase HUWE1 with an IC50 of 0.9 μM[1].

  • CAS Number: 1875036-75-1
  • MF: C25H28N8
  • MW: 440.54
  • Catalog: E1/E2/E3 Enzyme
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A