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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AN-2728

Crisaborole (AN-2728) is a potent inhibitor of PDE4 and cytokine release; inhibit PDE4 with an IC50 of 0.49 μM.

  • CAS Number: 906673-24-3
  • MF: C14H10BNO3
  • MW: 251.045
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 425.9±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 211.4±31.5 °C

lipoic acid

Lipoic acid ((R)-(+)-α-Lipoic acid) is an antioxidant, which is an essential cofactor of mitochondrial enzyme complexes. (R)-(+)-α-Lipoic acid is more effective than racemic Lipoic acid.

  • CAS Number: 1200-22-2
  • MF: C8H14O2S2
  • MW: 206.326
  • Catalog: Mitochondrial Metabolism
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 362.5±11.0 °C at 760 mmHg
  • Melting Point: 46-49ºC
  • Flash Point: 173.0±19.3 °C

BMS-779788

BMS-779788 is a LXR partial agonist with IC50 values of 68 nM for LXRα and 14 nM for LXRβ.

  • CAS Number: 918348-67-1
  • MF: C28H29ClN2O3S
  • MW: 509.060
  • Catalog: LXR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 738.7±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 400.6±35.7 °C

ATX inhibitor 18

ATX inhibitor 18 is a potent ATX inhibitor with an IC50 value of 24.2 nM. ATX inhibitor 18 shows antiproliferative activity and anti-fibrosis activity. ATX inhibitor 18 suppresses collagen deposition in TGF-β-mediated cardiac fibrosis[1].

  • CAS Number: 2402772-30-7
  • MF: C21H17Cl2FN6O
  • MW: 459.30
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IDO1-IN-19

IDO1-IN-19 (Compound 17) is a potent inhibitor of IDO1. IDO1-IN-19 has the potential for the research of cancer diseases[1].

  • CAS Number: 2328099-11-0
  • MF: C25H22F4N2O3
  • MW: 474.45
  • Catalog: Indoleamine 2,3-Dioxygenase (IDO)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SHP2-IN-6

SHP2-IN-6 is a potent SHP2 inhibitor, extracted from patent WO2017211303A1, compound 7, has an IC50 of 25.8 nM[1].

  • CAS Number: 2169223-48-5
  • MF: C22H26F2N6O2S
  • MW: 476.54
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MEDICA 16

MEDICA16, an ATP-citrate lyase inhibitor, significantly reduces intracellular TG content in gastrocnemius muscle, and this reduction is accompanied by an increase in insulin sensitivity. MEDICA16 is a selective agonist for GPR40 as well as selective partial agonists for GPR120[1][2].

  • CAS Number: 87272-20-6
  • MF: C20H38O4
  • MW: 342.513
  • Catalog: GPR120
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 485.9±18.0 °C at 760 mmHg
  • Melting Point: 154-159ºC
  • Flash Point: 261.8±17.7 °C

Tetrahydropiperin

Tetrahydropiperine, a cyclohexyl analogue of piperine, is the first natural aryl pentanamide from Piper longum[1]. Tetrahydropiperine (compound 14) inhibits the cytochrome P450 (CYP) isoform CYP1A1/arylhydrocarbon hydroxylase (AHH; IC50=23 µM)[2].

  • CAS Number: 23434-88-0
  • MF: C17H23NO3
  • MW: 289.369
  • Catalog: Cytochrome P450
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 469.9±24.0 °C at 760 mmHg
  • Melting Point: 41ºC
  • Flash Point: 238.0±22.9 °C

1(2H)-Pyrazineacetamide, 6-chloro-3-[[2,2-difluoro-2-(2-pyridinyl)ethyl]amino]-N-[(3-fluoro-2-pyridinyl)Methyl]-2-oxo-

Thrombin Inhibitor 2 is a small molecule direct thrombin inhibitor, extracted from US8541580B2. Thrombin Inhibitor 2 has antithrombotic activity[1].

  • CAS Number: 312904-62-4
  • MF: C19H16ClF3N6O2
  • MW: 452.81800
  • Catalog: Thrombin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Varespladib methyl

Varespladib methyl is a selective inhibitor of group II secretory phospholipase A2 (PLA2).

  • CAS Number: 172733-08-3
  • MF: C22H22N2O5
  • MW: 394.42000
  • Catalog: Phospholipase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PNU-103017

PNU-103017 is an HIV protease inhibitor.

  • CAS Number: 166335-18-8
  • MF: C28H28N2O5S
  • MW: 504.59700
  • Catalog: HIV
  • Density: 1.39g/cm3
  • Boiling Point: 738ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 400.1ºC

M435-1279

M435-1279 is a UBE2T inhibitor. M435-1279 acts inhibit the Wnt/β-catenin signaling pathway hyperactivation through blocking UBE2T-mediated degradation of RACK1[1].

  • CAS Number: 1359431-16-5
  • MF: C18H17N3O5S2
  • MW: 419.47
  • Catalog: E1/E2/E3 Enzyme
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S)-Bromoenol lactone

(S)-Bromoenol lactone ((S)-BEL) is an irreversible, chiral, mechanism-based inhibitor of calcium-independent phospholipase A2β (iPLA2β) that inhibits the vasopressin-induced release of arachidonate from cultured rat aortic smooth muscle (A10) cells with an IC50 of 2 µM[1].

  • CAS Number: 478288-94-7
  • MF: C16H13BrO2
  • MW: 317.177
  • Catalog: Phospholipase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 467.0±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 236.2±28.7 °C

KCL-286

Anticancer agent 168 is an orally active retinoic acid receptor (RAR/RXR) beta2 agonist with ameliorating effects on spinal cord injury (SCI)[1].

  • CAS Number: 1952276-71-9
  • MF: C19H14N2O4
  • MW: 334.33
  • Catalog: RAR/RXR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3,4-DIHYDROISOQUINOLINE-2(1H)-CARBOXIMIDAMIDE

Debrisoquin (Isocaramidine) is a TMPRSS2 inhibitors that inhibits SARS-CoV-2 entry into human lung cell line by a TMPRSS2-depedent manner, with an IC50 of 22μM. Debrisoquin can be used for antiviral research[1].

  • CAS Number: 1131-64-2
  • MF: C10H13N3
  • MW: 175.23
  • Catalog: SARS-CoV
  • Density: 1.24g/cm3
  • Boiling Point: 309.8ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 141.1ºC

CD437

CD437 is a selective Retinoic Acid Receptor γ (RARγ) agonist.

  • CAS Number: 125316-60-1
  • MF: C27H26O3
  • MW: 398.493
  • Catalog: RAR/RXR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 595.0±50.0 °C at 760 mmHg
  • Melting Point: 271.6-276ºC
  • Flash Point: 327.7±26.6 °C

Tauro-β-muricholic acid sodium

Tauro-β-muricholic Acid sodium (T-βMCA sodium), a endogenous metabolite, is a competitive and reversible farnesoid X receptor (FXR) antagonist, with an IC50 of 40 μM[1][2][3].

  • CAS Number: 145022-92-0
  • MF: C26H44NNaO7S
  • MW: 537.68
  • Catalog: FXR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Piclamilast

Piclamilast (RP 73401) is a phosphodiesterase 4 (PDE4) inhibitor, with IC50 values of 16 nM and 2 nM in pig aorta and eosinophil soluble, respectively[1][2][3][4].

  • CAS Number: 144035-83-6
  • MF: C18H18Cl2N2O3
  • MW: 381.253
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 447.8±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 224.6±28.7 °C

MK-8262

MK-8262 is an orally active and potent cholesteryl ester transfer protein (CETP) inhibitor with an IC50 of 53 nM and a log D of 5.3. MK-8262, a bistrifluoromethyl analogue, has the potential for coronary heart disease (CHD) correlated high-density lipoprotein (HDL) and low-density lipoprotein (LDL) research[1].

  • CAS Number: 1432054-03-9
  • MF: C35H25F9N2O5
  • MW: 724.57
  • Catalog: CETP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fosinopril sodium

Fosinopril Sodium is the ester prodrug of an angiotensin-converting enzyme (ACE) inhibitor, used for the treatment of hypertension and some types of chronic heart failure.Target: ACEFosinopril is a phosphinic acid-containing ester prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is rapidly hydrolyzed to fosinoprilat, its principle active metabolite. Fosinoprilat inhibits ACE, the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Fosinopril may be used to treat mild to moderate hypertension, as an adjunct in the treatment of congestive heart failure, and to slow the rate of progression of renal disease in hypertensive individuals with diabetes mellitus and microalbuminuria or overt nephropathy [1-3].

  • CAS Number: 88889-14-9
  • MF: C30H45NNaO7P
  • MW: 563.662
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 705.7±70.0 °C at 760 mmHg
  • Melting Point: 196-198ºC
  • Flash Point: 380.6±35.7 °C

Clomethiazole

Chlormethiazole is an potent and orally active GABAA agonist[1]. Chlormethiazole inhibits cytochrome P450 isoforms: CYP2A6 and CYP2E1 in human liver microsomes. Chlormethiazole is an anticonvulsant agent and has the potential for treating convulsive status epilepticus[2].

  • CAS Number: 533-45-9
  • MF: C6H8ClNS
  • MW: 198.11300
  • Catalog: GABA Receptor
  • Density: 1.218 g/cm3
  • Boiling Point: 245.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 102.4ºC

Trandolapril D5

Trandolapril D5 (RU44570 D5) is a deuterium labeled Trandolapril (RU44570). Trandolapril is an orally active angiotensin converting enzyme (ACE) inhibitor for hypertension and congestive heart failure (CHF)[1].

  • CAS Number: 1356847-98-7
  • MF: C24H29D5N2O5
  • MW: 435.57
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

H-Leu-Trp-Met-Arg-OH

H-Leu-Trp-Met-Arg-OH is a tetrapeptide. H-Leu-Trp-Met-Arg-OH can be used as a substrate for aminopeptidase-mediated hydrolysis studies[1].

  • CAS Number: 67368-23-4
  • MF: C28H44N8O5S
  • MW: 604.76500
  • Catalog: Aminopeptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Acetazolamide

Acetazolamide sodium is the sodium salt of Acetazolamide. Acetazolamide is a carbonic anhydrase (CA) IX inhibitor with an IC50 of 30 nM for hCA IX. Acetazolamide has diuretic, antihypertensive and anti-gonococcal activities[1][4][5][6].

  • CAS Number: 1424-27-7
  • MF: C4H5N4NaO3S2
  • MW: 244.22700
  • Catalog: Bacterial
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 258-259ºC (EFFERVESCENCE)
  • Flash Point: N/A

Entacapone sodium salt

Entacapone is a specific, potent, peripherally acting catechol-O-methyltransferase (COMT) inhibitor with IC50 of 151 nM for PD treatment. IC50 Value: 151 nMTarget: COMTin vitro: Entacapone inhibits catechol-O-methyltransferase(COMT) with similar IC50 in different tissues including live, duodenum, kidney and lung, but entacapone is more active than tolcapone in those tissues. Entacapone (< 100 μM) is a potent inhibitor of α-syn and β-amyloid (Aβ) oligomerization and fibrillogenesis, and also protects against extracellular toxicity induced by the aggregation of both proteins in PC12 cells.in vivo: Levodopa/carbidopa/entacapone has been shown to improve the pharmacokinetic profile of levodopa and provide superior symptomatic control compared with conventional levodopa/dopa decarboxylase inhibitor therapy. We report four case histories describing clinical experience of using levodopa/carbidopa/entacapone 200/50/200 mg, one of the latest doses of this formulation, in a range of patients with Parkinson's disease. These cases illustrate that levodopa/carbidopa/entacapone 200/50/200 mg provides improvements in symptomatic control.Clinical trial: The combination product carbidopa/levodopa/entacapone (CLE) was approved in 2003 for the treatment of PD patients.

  • CAS Number: 1047659-02-8
  • MF: C14H14N3NaO5
  • MW: 327.26800
  • Catalog: COMT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ODM-204

ODM-204 is novel nonsteroidal dual inhibitor of both androgen receptor and CYP17A1 enzyme, with IC50s of 80 nM and 22 nM, respectively.

  • CAS Number: 1642818-64-1
  • MF: C20H21F3N4
  • MW: 374.40
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Salvianolic acid A

Salvianolic acid A could protect the blood brain barrier through matrix metallopeptidase 9 (MMP-9) inhibition and anti-inflammation.

  • CAS Number: 96574-01-5
  • MF: C26H22O10
  • MW: 494.447
  • Catalog: MMP
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 858.7±65.0 °C at 760 mmHg
  • Melting Point: 164-167ºC
  • Flash Point: 292.9±27.8 °C

UVI 3003

UVI 3003 is a highly selective antagonist of retinoid X receptor (RXR), and inhibits xenopus and human RXRα in Cos7 cells, with IC50s of 0.22 and 0.24 μM, respectively.

  • CAS Number: 847239-17-2
  • MF: C28H36O4
  • MW: 436.58300
  • Catalog: RAR/RXR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HSP90-IN-20

HSP90-IN-20 (compound 78p) is a potent HSP90 inhibitor with an IC50 of ≤10 μM. HSP90-IN-20 has the potential for cancers research[1].

  • CAS Number: 747414-31-9
  • MF: C26H32N4O4
  • MW: 464.56
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PTP Inhibitor IV

PTP Inhibitor IV is a protein tyrosine phosphatase (PTP) inhibitor that competitively inhibits DUSP14 phosphatase activity with an 50 of 5.21 μM[1]. PTP Inhibitor IV inhibits SHP-2, PTP1B, PTP-ε, PTP Meg-2, PTP-σ, PTP-β, and PTP-μ with 50s of 1.8 μM, 2.5 μM, 8.4 μM, 13 μM, 20 μM, 6.4 μM, and 6.7 μM, respectively[2].

  • CAS Number: 329317-98-8
  • MF: C26H26F6N2O4S2
  • MW: 608.616
  • Catalog: Phosphatase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 578.0±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 303.4±32.9 °C