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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Ecopladib

Ecopladib is a sub-micromolar inhibitor of cytosolic phospholipase A2α (cPLA2α), with IC50s of 0.15 μM and 0.11 μM in the GLU micelle and rat whole blood assays, respectively.

  • CAS Number: 381683-92-7
  • MF: C39H33Cl3N2O5S
  • MW: 748.11400
  • Catalog: Phospholipase
  • Density: 1.35g/cm3
  • Boiling Point: 912.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 505.5ºC

Linrodostat (BMS-986205)

BMS-986205 is a selective indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor.

  • CAS Number: 1923833-60-6
  • MF: C24H24ClFN2O
  • MW: 410.15
  • Catalog: Indoleamine 2,3-Dioxygenase (IDO)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JE-2147

JE-2147 (AG1776) is a potent dipeptide protease inhibitor with a Ki of 0.33 nM for HIV-1 protease. JE-2147 has effective activities against a wide spectrum of HIV-1, HIV-2, simian immunodeficiency virus, and various clinical HIV-1 strains in vitro[1][2].

  • CAS Number: 186538-00-1
  • MF: C32H37N3O5S
  • MW: 575.71800
  • Catalog: HIV
  • Density: 1.258g/cm3
  • Boiling Point: 861.5ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 474.8ºC

PTP1B-IN-8

PTP1B-IN-8 is a potent and selective potent protein tyrosine phosphatase-1B (PTP1B) inhibitor extracted from patent CN103626692A, example 1[1].

  • CAS Number: 919091-61-5
  • MF: C19H13Cl4NO
  • MW: 413.12
  • Catalog: Phosphatase
  • Density: 1.463±0.06 g/cm3(Predicted)
  • Boiling Point: 607.5±55.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

Aloin

Aloin (mixture of A&B) is anthraquinone derivative isolated from Aloe vera. Aloin (mixture of A&B) has diverse biological activities such as anti-inflammatory, immunity, antidiabetic, antioxidant, antibacterial, antifungal, and antitumor activities. Aloin (mixture of A&B) also an effective inhibitor of stimulated granulocyte matrix metalloproteinases (MMPs)[1][2].

  • CAS Number: 8015-61-0
  • MF: C21H22O9
  • MW: 418.394
  • Catalog: Bacterial
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 752.6±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 268.0±26.4 °C

Morin 3-O-β-D-glucopyranoside

Morin 3-O-β-D-glucopyranoside is a natural flavonoid with antifungal, anticancer and antioxidant activities. Morin 3-O-β-D-glucopyranoside inhibits reverse transcriptase, protein-tyrosine kinase and xanthine oxidase, and also shows anti-HIV, antiarteriosclerotic, and superoxide scavenging activities[1].

  • Density: 1.87±0.1 g/cm3
  • Boiling Point: 875.2±65.0 °C
  • Melting Point: N/A
  • Flash Point: N/A

TM5441

TM5441 is a plasminogen activator inhibitor-1 (PAI-1); inhibits several tumor cell lines with IC50 values between 9.7 and 60.3 μM.

  • CAS Number: 1190221-43-2
  • MF: C21H17ClN2O6
  • MW: 428.829
  • Catalog: PAI-1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

18-Oxocortisol

18-Oxocortisol is a derivative of cortisol that is produced by aldosterone synthase (CYP11B2). 18-Oxocortisol is a naturally occurring mineralocorticoid agonist. 18-Oxocortisol is a biomarker in adrenal vein sampling[1][2][3].

  • CAS Number: 2410-60-8
  • MF: C21H28O6
  • MW: 376.44300
  • Catalog: Mineralocorticoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aminopeptidase-IN-1

Aminopeptidase-IN-1 (compound 16o) is a potent insulin-regulated aminopeptidase (IRAP) inhibitor with an Ki value of 7.7 μM. Aminopeptidase-IN-1 can be used tor research cognitive and memory impairments[1].

  • CAS Number: 374102-08-6
  • MF: C18H16N2O6
  • MW: 356.33
  • Catalog: Aminopeptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PFKFB3-IN-2

PFKFB3-IN-2 is a 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) inhibitor. PFKFB3-IN-2 has potential applications in cancer, neurodegenerative diseases, autoimmune diseases, inflammatory diseases, multiple sclerosis, metabolic diseases, angiogenesis inhibition and other diseases[1].

  • CAS Number: 794552-84-4
  • MF: C14H11NO7S
  • MW: 337.30
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-4950834

PF-4950834 is a potent, selective, orally bioavailable, ATP-competitive rho kinase inhibitor with IC50 values of 8.35 nM and 33.12 nM against ROCK2 and ROCK1, respectively. PF-4950834 inhibits neutrophil migration[1].

  • CAS Number: 1256264-62-6
  • MF: C21H19N3O2
  • MW: 345.39
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-03049423

PF-03049423 is a potent, selective, orally active, and brain penetrant inhibitor of PDE5 with IC50 of 0.2 nM; displays 158-fold and 2460-fold selectivity over PDE6 and PDE11, respectively; possesses an excellent potency and selectivity profile and demonstrates robust in vivo blood pressure lowering in a spontaneously hypertensive rat (SHR) model. Stroke Phase 2 Discontinued

  • CAS Number: 402955-58-2
  • MF: C24H32N6O4
  • MW: 505.010
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

sPLA2 (Type III)

Phospholipase A2 (PLA2) catalyzes the hydrolysis of the sn-2 position of membrane glycerophospholipids to liberate arachidonic acid (AA). Phospholipase A2 is a member of the class of heat-stable, calcium-dependent enzymes, is often used in biochemical studies[1].

  • CAS Number: 9001-84-7
  • MF:
  • MW:
  • Catalog: Phospholipase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cysteine Protease inhibitor

Cysteine Protease inhibitor is an inhibitor of cysteine protease. IC50 & Target: Cysteine Protease

  • CAS Number: 921625-62-9
  • MF: C18H14N4O
  • MW: 302.33000
  • Catalog: Cathepsin
  • Density: 1.30±0.1 g/cm3 (20 °C, 760 mmHg)
  • Boiling Point: 540.9±60.0 °C (760 mmHg)
  • Melting Point: N/A
  • Flash Point: N/A

Tyr-Phe

H-Tyr-Phe-OH (L-Tyrosyl-L-phenylalanine) is an orally active inhibitor of Angiotensin converting enzyme (ACE), with an inhibiton rate of 48% at 50 μM. H-Tyr-Phe-OH can be used as an biomarker for differentiating benign thyroid nodules (BTN) from thyroid cancer (TC). H-Tyr-Phe-OH exhibits xanthine oxidase inhibition (uric acid lowering) activity and serves as regulator in IL-8 production in neutrophil-like cells[1][2][3][4].

  • CAS Number: 17355-11-2
  • MF: C18H20N2O4
  • MW: 328.36200
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: 1.3 g/cm3
  • Boiling Point: 642.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 342.2ºC

Cordycepin

Cordycepin, which is a nucleoside derivative isolated from Cordyceps, inhibits IL-1β-induced MMP-1 and MMP-3 expression in rheumatoid arthritis synovial fibroblasts (RASFs) in a dose-dependent manner.

  • CAS Number: 73-03-0
  • MF: C10H13N5O3
  • MW: 251.242
  • Catalog: MMP
  • Density: 1.9±0.1 g/cm3
  • Boiling Point: 627.2±65.0 °C at 760 mmHg
  • Melting Point: 225-229ºC
  • Flash Point: 333.1±34.3 °C

edaravone

Edaravone is a strong novel free radical scavenger, and inhibits MMP-9-related brain hemorrhage in rats treated with tissue plasminogen activator.

  • CAS Number: 89-25-8
  • MF: C10H10N2O
  • MW: 174.199
  • Catalog: MMP
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 333.0±11.0 °C at 760 mmHg
  • Melting Point: 126-128 °C(lit.)
  • Flash Point: 155.2±19.3 °C

GSK3839919A

GSK3839919A is a potent and allosteric HIV-1integrase inhibitor[1].

  • CAS Number: 2081127-77-5
  • MF: C36H46ClN3O3
  • MW: 604.22
  • Catalog: HIV Integrase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

QUINIDINE SULFATE (2:1) (salt)

Quinidine Monosulfate is an antiarrhythmic agent. Quinidine Monosulfate is a potent, orally active, selective cytochrome P450db inhibitor. Quinidine Monosulfate is also a K+ channel blocker with an IC50 of 19.9 μM. Quinidine Monosulfate can be used for malaria research[1][2][3].

  • CAS Number: 50-54-4
  • MF: C40H50N4O8S
  • MW: 746.91200
  • Catalog: Potassium Channel
  • Density: N/A
  • Boiling Point: 495.9ºC at 760mmHg
  • Melting Point: 212ºC
  • Flash Point: 253.7ºC

Benazepril

Benazepril, an angiotensin converting enzyme inhibitor, which is a medication used to treat high blood pressure.Target: angiotensin converting enzyme (ACE)Benazepril is a medication used to treat high blood pressure (hypertension), congestive heart failure, and chronic renal failure. Upon cleavage of its ester group by the liver, benazepril is converted into its active form benazeprilat, a non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor [1].Animals were randomly divided into 4 groups: sham STNx group (control), STNx group, morning benazepril group (MB) and evening benazepril group (EB).Benazepril was intragastrically administered at a dose of 10 mg/kg/day at 07:00 and 19:00 in the MB group and EB group respectively for 12 weeks. All the animals were synchronized to the light:dark cycle of 12:12 for 12 weeks. Systolic blood pressure (SBP), 24-h urinary protein excretion and renal function were measured at 11 weeks. Blood samples and kidneys were collected every 4 h throughout a day to detect the expression pattern of renin activity (RA), angiotensin II (AngII) and aldosterone (Ald) by radioimmunoassay (RIA) and the mRNA expression profile of clock genes (bmal1, dbp and per2) by real-time PCR at 12 weeks. Our results showed that no significant differences were noted in the SBP, 24-h urine protein excretion and renal function between the MB and EB groups. There were no significant differences in average Ald and RA content of a day between the MB group and EB group. The expression peak of bmal1 mRNA was phase-delayed by 4 to 8 h, and the diurnal variation of per2 and dbp mRNA diminished in the MB and EB groups compared with the control and STNx groups. It was concluded when the similar SBP reduction, RAAS inhibition and clock gene profile were achieved with optimal dose of benazepril, morning versus evening dosing of benazepril has the same renoprotection effects [2].Clinical indications: Congestive heart failure; End stage renal disease; HypertensionFDA Approved Date: Toxicity: headaches; cough; Anaphylaxis; angioedema; hyperkalemia

  • CAS Number: 86541-75-5
  • MF: C24H28N2O5
  • MW: 424.490
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 691.2±55.0 °C at 760 mmHg
  • Melting Point: 133-135 °C(lit.)
  • Flash Point: 371.8±31.5 °C

DMU2139(CYP1B1 inhibitor 6j)

DMU2139 is a potent and specific CYP1B1 inhibitor, with IC50s of 9 nM and 795 nM for CYP1B1 and CYP1A1, respectively.

  • CAS Number: 1821143-80-9
  • MF: C19H15NO2
  • MW: 289.33
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HFI-142

HFI-142 is an insulin-regulated aminopeptidase (IRAP) inhibitor with a ki of 2.01 μM[1].

  • CAS Number: 332164-34-8
  • MF: C17H16N2O4
  • MW: 312.32
  • Catalog: Aminopeptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bezeparsen

Bezeparsen is a PCSK9 synthesis inhibitor[1].

  • CAS Number: 2639640-84-7
  • MF: C238H335N67O113P16S15
  • MW: 6919.13
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GW280264X

GW280264X is the mixed ADAM10/TACE (ADAM17) metalloproteinases inhibitor. GW280264X potently blocks TACE (ADAM17) and ADAM10 with IC50s of 8.0 nM and 11.5 nM, respectively[1]. ADAM10 and 17 modulate the immunogenicity of glioblastoma-initiating cells[2].

  • CAS Number: 866924-39-2
  • MF: C28H41N5O6S
  • MW: 575.72
  • Catalog: MMP
  • Density: 1.229±0.06 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Atorvastatin hemicalcium trihydrate

Atorvastatin hemicalcium trihydrate is an orally active HMG-CoA reductase inhibitor, has the ability to effectively decrease blood lipids. Atorvastatin hemicalcium trihydrate inhibits human SV-SMC proliferation and invasion with IC50s of 0.39 μM and 2.39 μM, respectively[1][2][3].

  • CAS Number: 344920-08-7
  • MF: C33H35FN2O5.1/2Ca.3H2O
  • MW: 632.73
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MMP145

MMP145 (compound 27) is a potent, selective and orally active MMP-12 inhibitor. MMP145 is effective in inflammation and asthma reasearch[1].

  • CAS Number: 1025717-75-2
  • MF: C20H20N2O7S
  • MW: 432.44700
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tolrestat

Tolrestat is a potent, orally active aldose reductase inhibitor with IC50 of 35 nM.

  • CAS Number: 82964-04-3
  • MF: C16H14F3NO3S
  • MW: 357.348
  • Catalog: Aldose Reductase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 498.1±55.0 °C at 760 mmHg
  • Melting Point: 164-165°
  • Flash Point: 255.0±31.5 °C

Telotristat

Telotristat ethyl (LX1606) is a novel, orally-delivered inhibitor of tryptophan hydroxylase that reduces serotonin production.

  • CAS Number: 1033805-22-9
  • MF: C27H26ClF3N6O3
  • MW: 574.982
  • Catalog: Tryptophan Hydroxylase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 704.7±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 380.0±35.7 °C

3,4-Dimethoxyphenol

3,4-Dimethoxyphenol is a plant-derived phenylpropanoid compound and can use as a whitening agent in cosmetics. 3,4-Dimethoxyphenol has tyrosinase-inhibiting activity[1]. 3,4-Dimethoxyphenol has potent antioxidant effect isolated from the bacterial fermentation broth[2].

  • CAS Number: 2033-89-8
  • MF: C8H10O3
  • MW: 154.163
  • Catalog: Tyrosinase
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 271.2±20.0 °C at 760 mmHg
  • Melting Point: 79-82 °C(lit.)
  • Flash Point: 117.8±21.8 °C

1-Isopropyltryptophan

1-Isopropyltryptophan (1-IsoPT) is a IDO1 inhibitor. 1-Isopropyltryptophan decreases the expression of IFN-γ stimulated ID0-1 and ID0-2 mRNA[1].

  • CAS Number: 1219485-46-7
  • MF: C14H18N2O2
  • MW: 246.30
  • Catalog: Indoleamine 2,3-Dioxygenase (IDO)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A