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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Lonafarnib

Lonafarnib is an orally bioavailable farnesyl protein transferase (FPTase) inhibitor for H-ras, K-ras and N-ras with IC50 of 1.9 nM, 5.2 nM and 2.8 nM, respectively.

  • CAS Number: 193275-84-2
  • MF: C27H31Br2ClN4O2
  • MW: 638.822
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 710.4±70.0 °C at 760 mmHg
  • Melting Point: 214.5-215.9° (monohydrate); mp 222-223°
  • Flash Point: 383.5±35.7 °C

Isosilybin

Isosilybin (Isosilybinin) is a flavonoid from milk thistle; inhibits CYP3A4 induction with an IC50 of 74 μM.

  • CAS Number: 72581-71-6
  • MF: C25H22O10
  • MW: 482.436
  • Catalog: Cytochrome P450
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 793.0±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 274.5±26.4 °C

Rosiptor

Rosiptor is an activator of SH2-containing inositol-5'-phosphatase 1 (SHIP1).

  • CAS Number: 782487-28-9
  • MF: C20H35NO2
  • MW: 321.497
  • Catalog: Phosphatase
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 451.6±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 226.9±28.7 °C

MMPI-1154

MMPI-1154 is a small molecule MMP-2 inhibitor with IC50 of 10/6.6/13/1.8 uM for MMP1/2/9/13, respectively; shows significant cardio-cytoprotecion, significantly decreases infarct size when applied at 1 μM in an ex vivo model for acute myocardial infarction.

  • CAS Number: 1382722-47-5
  • MF: C26H24FN3O3
  • MW: 445.494
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MLN4924 (hydrochloride)

Pevonedistat hydrochloride (MLN4924 hydrochloride) is a potent and selective NEDD8-activating enzyme (NAE) inhibitor, with an IC50 of 4.7 nM.

  • CAS Number: 1160295-21-5
  • MF: C21H26ClN5O4S
  • MW: 479.98000
  • Catalog: NEDD8-activating Enzyme
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CAY10650

CAY10650 is a highly potent cytosolic phospholipase A2α (cPLA2α) inhibitor with an IC50 value of 12 nM.IC50 value: 12 nMTarget: cPLA2CAY10650 is a highly potent (IC50 = 12 nM) cPLA2α inhibitor. It demonstrates strong anti-inflammatory effects when applied topically at a dose of 0.1 mg/ear in a mouse model of acute irritant contact dermatitis. Chinese hamsters (n = 6/group) were infected with parasite-laden contact lenses and treated with cPLA2α inhibitors (AACOCF3 and CAY10650) 50 μg/5 μl was injected with topical eye-drop under the contact lens of an infected cornea three times a day for 6 days and topically on days 7–14 postinfection. Animals were anesthetized and sacrificed 15 days after application of cPLA2α inhibitors. Treatment with the AACOCF3 and CAY10650 had a profound effect on the severity and chronicity of keratitis. In addition, hamsters treated with AACOCF3 had significantly less severe keratitis as compared with CAY10650 group.

  • CAS Number: 1233706-88-1
  • MF: C28H25NO6
  • MW: 471.501
  • Catalog: Phospholipase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 685.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 368.3±31.5 °C

LX-1031

LX-1031 is a potent, orally available tryptophan 5-hydroxylase (TPH) inhibitor that reduces serotonin (5-HT) synthesis peripherally.

  • CAS Number: 945976-76-1
  • MF: C28H25F3N4O4
  • MW: 538.518
  • Catalog: Tryptophan Hydroxylase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 715.6±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 386.6±35.7 °C

Apratastat

Apratastat is an orally active, potent, and reversible dual inhibitor of tumor necrosis factor-α converting enzyme (TACE) and matrix metalloproteinases (MMPs) . Apratastat can potently inhibit the release of TNF-α in vitro, ex vivo, and in vivo with IC50s of 144 ng/mL in vitro and 81.7 ng/mL ex vivo, respectively[1].

  • CAS Number: 287405-51-0
  • MF: C17H22N2O6S2
  • MW: 414.496
  • Catalog: TNF Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TAK-243(MLN7243)

TAK-243 is a potent and selective ubiquitin-like modifier activating enzyme 1 (UBA1) inhibitor.

  • CAS Number: 1450833-55-2
  • MF: C19H20F3N5O5S2
  • MW: 519.518
  • Catalog: E1/E2/E3 Enzyme
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dnp-(Leu421)-Collagen Type VIII α1 Chain (419-426) amide (human, mouse) trifluoroacetate salt

Dnp-GPLGMRGL-NH2 is a peptide substrate for matrix metalloproteinase-13 (MMP-13) with a kcat/Km value of 4,200,000 M-1s-1.

  • CAS Number: 1872435-02-3
  • MF: C40H64N14O12S
  • MW: 965.1
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Omeprazole sodium monohydrate

Omeprazole sodium (H 16868 sodium), a proton pump inhibitor (PPI), is available for treatment of acid-related gastrointestinal disorders. Omeprazole sodium shows competitive inhibition of CYP2C19 activity with a Ki of 2 to 6 μM[1]. Omeprazole sodium also inhibits growth of Gram-positive and Gram-negative bacteria[2]. Omeprazole is a potent brain penetrant neutral sphingomyelinase (N-SMase) inhibitor (exosome inhibitor)[3].

  • CAS Number: 95510-70-6
  • MF: C17H20N3NaO4S
  • MW: 385.413
  • Catalog: Bacterial
  • Density: 1.37g/cm3
  • Boiling Point: 600ºC at 760mmHg
  • Melting Point: 220°C
  • Flash Point: 316.7ºC

Hydrangenol

Hydrangenol is an orally active antiphotoaging compound. It can be isolated from Hydrangea serrata leaves. Hydrangenol prevents wrinkle formation by reducing MMP and inflammatory cytokine expression and increasing moisturizing factors and antioxidant genes level[1].

  • CAS Number: 480-47-7
  • MF: C15H12O4
  • MW: 256.253
  • Catalog: COX
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 528.3±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 206.4±23.6 °C

TD-0212

TD-0212 (compound 35) is an orally active dual pharmacology angiotensin II type 1 receptor (AT1) antagonist and neprilysin (NEP) inhibitor, with a pKi of 8.9 for AT1 and a pIC50 of 9.2 for NEP[1].

  • CAS Number: 1073549-10-6
  • MF: C28H34FN3O4S
  • MW: 527.65
  • Catalog: Angiotensin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tropolone

Tropolone, a  tropone derivative with a hydroxyl group in the 2-position, is a precursor of manyazulene derivatives such as methyl 2-methylazulene-1-carboxylate[1]. Tropolone is a potent inhibitor of mushroom tyrosinase with a IC50 of 0.4 μM, and the inhibition can be reversed by dialysis or by excess CU2+[2].

  • CAS Number: 533-75-5
  • MF: C7H6O2
  • MW: 122.121
  • Catalog: Tyrosinase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 290.1±33.0 °C at 760 mmHg
  • Melting Point: 50-52 °C(lit.)
  • Flash Point: 122.0±18.0 °C

Rpn11-IN-1

Rpn11-IN-1 is a potent and selective inhibitor of proteasome subunit Rpn11 with an IC50 of 390 nM.

  • CAS Number: 2084867-65-0
  • MF: C15H13N3OS2
  • MW: 315.41
  • Catalog: Proteasome
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SC 22716

SC-22716 is a potent, competitive, reversible inhibitor of human LTA4 hydrolase, with an IC50 of 0.20 µM. SC-22716 has potential for the research of inflammatory bowel disease (IBD) and psoriasis[1].

  • CAS Number: 262451-89-8
  • MF: C18H21NO
  • MW: 267.36500
  • Catalog: Aminopeptidase
  • Density: 1.065g/cm3
  • Boiling Point: 418.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 122.8ºC

Finerenone

Finerenone (BAY 94-8862) is a third-generation, selective, and orally available nonsteroidal mineralocorticoid receptor (MR) antagonist (IC50=18 nM). Finerenone displays excellent selectivity versus glucocorticoid receptor (GR), androgen receptor (AR), and progesterone receptor (>500-fold). Finerenone has the potential for cardiorenal diseases research, such as type 2 diabetes mellitus and chronic kidney disease[1][2].

  • CAS Number: 1050477-31-0
  • MF: C21H22N4O3
  • MW: 378.42400
  • Catalog: Mineralocorticoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ENPROFYLLINE

Enprofylline acts as a selective and competitive A2B receptor antagonist with the Ki of 7 μM. Enprofylline also acts as a phosphodiesterase inhibitor. Enprofylline can be used for the research of asthma, chronic obstructive pulmonary disease[1][2][3].

  • CAS Number: 41078-02-8
  • MF: C8H10N4O2
  • MW: 194.19100
  • Catalog: Adenosine Receptor
  • Density: 1.367 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Proteasome Substrate II

Z-Leu-Leu-Glu-AMC is a substrate peptide, and can be used for determination of postacidic-like hydrolysing activity of 20S proteasome[1]

  • CAS Number: 348086-66-8
  • MF: C35H44N4O9
  • MW: 664.745
  • Catalog: Proteasome
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 967.8±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 539.1±34.3 °C

Pregnenolone 16α-carbonitrile

Pregnenolone 16α-carbonitrile is an orally active prototypical and effective rodent-PXR activator. Pregnenolone 16α-carbonitrile, a synthetic steroid, induces cytochrome P4503A expression. Pregnenolone 16α-carbonitrile exhibits increased resistance to subsequent stressful insults[1][2][3].

  • CAS Number: 1434-54-4
  • MF: C22H31NO2
  • MW: 341.487
  • Catalog: Cytochrome P450
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 508.5±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 261.3±30.1 °C

Methazolamide

Methazolamide is a carbonic anhydrase inhibitor used to treat glaucoma.Target: Carbonic AnhydraseMethazolamide is a carbonic anhydrase inhibitor with Ki of 50 nM, 14 nM and 36 nM for hCA I, hCA II and bCA IV isoforms, respectively [1]. Methazolamide is of strength equal to acetazolamide, another carbonic anhydrase inhibitor used to treat irregular breathing disorders. However, methazolamide differs from acetazolamide in that it fails to activate Ca2+-dependent potassium channels in skeletal muscles. Methazolamide does not impair respiratory work performance in anesthetized rabbits [2]. Oral administration of methazolamide decreases IOPs and AHFRs in clinically normal dogs, with effectiveness diminishing in the evening [3].

  • CAS Number: 554-57-4
  • MF: C5H8N4O3S2
  • MW: 236.272
  • Catalog: Carbonic Anhydrase
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: 402.0±28.0 °C at 760 mmHg
  • Melting Point: 208ºC (dec.)
  • Flash Point: 196.9±24.0 °C

Z-Arg-Arg-pNA

Z-Arg-Arg-pNA is a substrate for cathepsin B and can be used to detect this enzyme activity[1].

  • CAS Number: 122630-71-1
  • MF: C26H36N10O6
  • MW: 584.63
  • Catalog: Cathepsin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ACC1/2-IN-2

ACC1/2-IN-1 (compound 4s) is a potent ACC1/2 inhibitor with IC50 values of 98.06 and 29.43 nM for ACC1 and ACC2, respectively. ACC1/2-IN-1 can be used for cancer research[1].

  • CAS Number: 1031411-94-5
  • MF: C24H25N3O3
  • MW: 403.47
  • Catalog: Acetyl-CoA Carboxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PAZ-417

Aleplasinin is an orally active, potent, BBB-penetrated and selectiveSERPINE1 (PAI-1, Plasminogen activator inhibitor-1) inhibitor. Aleplasinin increases amyloid-β (Aβ) catabolism and ameliorates amyloid-related pathology. Aleplasinin improves memory deficiency. Aleplasinin can be used for Alzheimer's disease research[1][2].

  • CAS Number: 481629-87-2
  • MF: C28H27NO3
  • MW: 425.51900
  • Catalog: PAI-1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-4981517

CYP3cide (PF-4981517) is a potent, selective and time-dependent inhibitor of cytochrome P4503A4 (CYP3A4). The IC50 values for Midazolam 1’-hydroxylase activity are 0.03 μM, 17 μM, and 71 μM for CYP3A4, CYP3A5, and CYP3A7, respectively. CYP3cide can be used to distinguish the contributions of CYP3A4 versus CYP3A5 on drug metabolism[1].

  • CAS Number: 1390637-82-7
  • MF: C26H32N8
  • MW: 456.586
  • Catalog: Cytochrome P450
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 630.2±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 334.9±31.5 °C

CD 2314

CD2314 is a potent and selective RARβ receptor agonist with a Kd of 195 nM in S91 melanoma cells[1].

  • CAS Number: 170355-37-0
  • MF: C23H24O2S
  • MW: 364.50000
  • Catalog: RAR/RXR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Doxycycline

Doxycycline monohydrate is an antibiotic and broad-spectrum metalloproteinase (MMP) inhibitor[1][2][3][4].

  • CAS Number: 17086-28-1
  • MF: C22H26N2O9
  • MW: 462.450
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: 819.4ºC at 760 mmHg
  • Melting Point: 167-168℃
  • Flash Point: 449.4ºC

Hsp90-IN-17

Hsp90-IN-17 (Example 5) is an HSP90 inhibitor that can be used in the study of proliferative diseases, such as cancer and neurodegenerative diseases[1].

  • CAS Number: 1253584-78-9
  • MF: C21H20N4O7
  • MW: 440.41
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Elvitegravir(GS-9137,JTK-303)

Elvitegravir is an HIV integrase inhibitor for HIV-1IIIB, HIV-2EHO and HIV-2ROD with IC50 of 0.7 nM, 2.8 nM and 1.4 nM, respectively.

  • CAS Number: 697761-98-1
  • MF: C23H23ClFNO5
  • MW: 447.884
  • Catalog: HIV
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 623.6±55.0 °C at 760 mmHg
  • Melting Point: 93-96°C
  • Flash Point: 330.9±31.5 °C

Deserpidine

Deserpidine (Harmonyl) is an alkaloid isolated from the root of Rauwolfia canescens related to Reserpine. Deserpidine is used as an antihypertensive agent and a tranquilizer. Deserpidine is a competitive angiotensin converting enzyme (ACE) inhibitor. Deserpidine also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex[1][2][3].

  • CAS Number: 131-01-1
  • MF: C32H38N2O8
  • MW: 578.653
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 676.1±55.0 °C at 760 mmHg
  • Melting Point: ~275 °C (dec.)(lit.)
  • Flash Point: 362.7±31.5 °C