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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URB597

URB597 is a potent, orally bioavailable FAAH inhibitor with IC50 of 4.6 nM, with no activity on other cannabinoid-related targets.IC50 value: 4.6 nM [1]Target: FAAH in vitro: URB597 binds in the hydrophobic pocket and catalytic core of FAAH that connects the active site residues to the membrane surface of FAAH [1]. URB597 reduces the expression of the LPS-induced enzymes cyclo-oxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS; NOS2) in primary rat microglial cell, with a concomitant reduction in the release of the inflammatory mediators prostaglandin E2 (PGE2) and (NO) nitric oxide [2]. in vivo: URB597 inhibits [3H]anandamide hydrolysis in rat brain membranes with a parallel increase in brain anandamide, OEA, and PEA content by inhibition of FAAH. URB597 enhances the hypothermia effect induced by ethanolamide by inhibiting FAAH [3]. When delivered intraperitonealy (0.3 mg/kg) URB597 reduces allodynia and hyperalgesia through cannabinoid CB1 and CB2 receptor-mediated analgesia in rats with inflammatory pain [4].

  • CAS Number: 546141-08-6
  • MF: C20H22N2O3
  • MW: 338.400
  • Catalog: Autophagy
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 533.2±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 276.3±30.1 °C

RORγt inhibitor 1

A potent, selective, orally bioavailable RORγt inverse agonist with IC50 of 17 nM in TR-FRET assays; shows no inhibitory activity against the closely related nuclear hormone receptors RORα or RORβ; attenuates expression of genes such as IL26, IL23R and CCR6 in primary human Th17 cells, attenuate the knee swelling response in an antigen-induced arthritis rat models and inhibits IL-17A cytokine production in ex vivo recall assays.

  • CAS Number: 2079892-79-6
  • MF: C26H33N7O2
  • MW: 475.597
  • Catalog: ROR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IDO-IN-8

IDO-IN-8 (NLG-1487) is an indoleamine 2,3-dioxygenase (IDO) inhibitor extracted from patent WO WO2012142237A1, compound 1487, has an IC50 of 1-10 μM.

  • CAS Number: 1402837-77-7
  • MF: C18H21FN2O2
  • MW: 316.370
  • Catalog: Indoleamine 2,3-Dioxygenase (IDO)
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 555.4±35.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 289.7±25.9 °C

1-Deazaadenosine

1-Deazaadenosine is a potent Adenosine deaminase (ADA) inhibitor with a Ki value of 0.66 μM. 1-Deazaadenosine exhibits anti-cancer activities in vitro and has the potential to be a chemotherapy agent for lymphoproliferative disorders[1][2].

  • CAS Number: 14432-09-8
  • MF: C11H14N4O4
  • MW: 266.25300
  • Catalog: Adenosine Deaminase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Statil

Statil (Ponalrestat) is an orally active, selective and noncompetitive aldose reductase (AKR1B1; ALR) inhibitor. Statil selectively inhibits ALR2 (Ki=7.7 nM) over ALR1 (Ki=60 μM). Statil inhibits the conversion of glucose to sorbitol[1][2][3].

  • CAS Number: 72702-95-5
  • MF: C17H12BrFN2O3
  • MW: 391.191
  • Catalog: Aldose Reductase
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 576.3±60.0 °C at 760 mmHg
  • Melting Point: 184-186ºC (DEC.)
  • Flash Point: 302.4±32.9 °C

Suc-Ala-Ala-Pro-Phe-SBzl

Suc-Ala-Ala-Pro-Phe-SBzl can be used as the substrate of rat intestinal mast cell protease (RMCP I), rat skeletal muscle mast cell protease (RMCP II) and Chymotrypsin (HY-108910). Suc-Ala-Ala-Pro-Phe-SBzl can be hydrolyzed by glycine (R208G)[1][2].

  • CAS Number: 80651-95-2
  • MF: C31H38N4O7S
  • MW: 610.72100
  • Catalog: Proteasome
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HIF-1 inhibitor-4

HIF-1 inhibitor-4 is a HIF-1 inhibitor (IC50: 560 nM). HIF-1 inhibitor-4 reduces the HIF-1α protein level without affecting its mRNA level[1].

  • CAS Number: 333357-56-5
  • MF: C18H19IN2O2
  • MW: 422.26013
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VTP-27999

VTP-27999 is an alkyl amine Renin inhibitor; VTP-27999 is useful for Hypertension and End-Organ Diseases.Ic50 value:Target: Renin

  • CAS Number: 942142-51-0
  • MF: C26H41ClN4O5
  • MW: 525.08100
  • Catalog: Renin
  • Density: 1.178g/cm3
  • Boiling Point: 703.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 379ºC

2,6-Dimethylquinoline

2,6-Dimethylquinoline, a nature constituent from the roots of Peucedantu praeruptorum, is a CYP1A2 inhibitor with an IC50 of 3.3 µM. 2,6-Dimethylquinoline also inhibits CYP2B6 activity with an IC50 of 480 µM[1][2][3].

  • CAS Number: 877-43-0
  • MF: C11H11N
  • MW: 157.212
  • Catalog: Cytochrome P450
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 266.5±0.0 °C at 760 mmHg
  • Melting Point: 57-59 °C(lit.)
  • Flash Point: 106.5±11.3 °C

3-hydroxy-3-methylglutaric acid

Meglutol is an antilipemic agent which lowers cholesterol, triglycerides, serum beta-lipoproteins and phospholipids, and inhibits the activity of hydroxymethylglutarryl CoA reductases, which is the rate limiting enzyme in the biosynthesis of cholesterol.

  • CAS Number: 503-49-1
  • MF: C6H10O5
  • MW: 162.14100
  • Catalog: HMG-CoA Reductase (HMGCR)
  • Density: 1.417 g/cm3
  • Boiling Point: 120 °C / 13mmHg
  • Melting Point: 105-108 °C(lit.)
  • Flash Point: 182.2ºC

hCAIX-IN-5

hCAIX-IN-5 (compound 6b) is a potent and selective hCAIX inhibitor with KIs of >10000, >10000, 130.7, 829.1 nM for hCAI, hCAII, hCAIV, hCAIX, respectively[1].

  • CAS Number: 2451479-57-3
  • MF: C18H12FNO3
  • MW: 309.29
  • Catalog: Carbonic Anhydrase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Z-Leu-Leu-Tyr-α-keto aldehyde

Z-Leu-Leu-Tyr-COCHO is a potent chymotrypsin-like activity inhibitor with a Ki value of 3.0 nM[1].

  • CAS Number: 204649-66-1
  • MF: C30H39N3O7
  • MW: 553.65
  • Catalog: Proteasome
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 813.3±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 445.6±34.3 °C

Dazcapistat

Dazcapistat is a potent calpain inhibitor, with IC50s of <3 μM for calpain 1, calpain 2 and calpain 9, respectively (patent WO2018064119A1, compound 405)[1].

  • CAS Number: 2221010-42-8
  • MF: C21H18FN3O4
  • MW: 395.38
  • Catalog: Proteasome
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Orismilast

Orismilast (LEO-32731) is a PDE4 inhibitor used for the research of inflammatory diseases[1].

  • CAS Number: 1353546-86-7
  • MF: C19H15Cl2F2NO7S
  • MW: 510.29
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 788.8±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 430.9±32.9 °C

Talarozole (R enantiomer)

Talarozole R enantiomer is a potent and selective inhibitor of cytochrome P450 26-mediated breakdown of endogenous all-trans retinoic acid for the treatment of psoriasis and acne.Target: CYP26in vitro: Talarozole R enantiomer treatment increased the mRNA expression of CRABP2, KRT4, CYP26A1 and CYP26B1 dose dependently, and decreased theexpression of KRT2 and IL-1alpha compared with vehicle-treated skin. No mRNA change in retinol-metabolizing enzymes was obtained. There was no induction of epidermal thickness or overt skin inflammation in talarozole-treated skin. Immunofluorescence analysis confirmed an upregulation of KRT4 protein, but no upregulation of CYP26A1 and CYP26B1 expression was detected [1] [2].in vivo: Talarozole R enantiomer slightly diffused into the skin only when dissolved in propylene glycol, isopropyl myristate or ethanol. Although only 0.1% of the dose applied was found in the skin itself after 12-24 h, this was sufficient to achieve local concentrations well above the half-maximal inhibitory concentration value for talarozole. The distribution of talarozole within the skin was investigated: 80% was located in the epidermis, while the remaining 20% was found in the dermis [3].

  • CAS Number: 870093-23-5
  • MF: C21H23N5S
  • MW: 377.50600
  • Catalog: Cytochrome P450
  • Density: 1.26
  • Boiling Point: 561.016ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 293.092ºC

Z-Ala-Arg-Arg-AMC hydrochloride salt

Z-Ala-Arg-Arg-AMC (Fluorogenic Proteasome Substrate) is a fluorogenic substrate for assaying trypsin-like activity of proteasome[1].

  • CAS Number: 90468-18-1
  • MF: C33H44N10O7
  • MW: 692.76500
  • Catalog: Proteasome
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Palmitic acid-1-13C

Palmitic acid-1-13C is the 13C-labeled Palmitic acid. Palmitic acid is a long-chain saturated fatty acid commonly found in both animals and plants. Palmitic acid can induce the expression of glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in in mouse granulosa cells[1][2].

  • CAS Number: 57677-53-9
  • MF: C1513CH32O2
  • MW: 257.41700
  • Catalog: HSP
  • Density: 0.855 g/mL at 25ºC
  • Boiling Point: 271.5ºC100 mm Hg(lit.)
  • Melting Point: 61-64ºC(lit.)
  • Flash Point: N/A

Cathepsin Inhibitor 2

Cathepsin Inhibitor 2 is a potent Cathepsin S inhibitor extracted from patent WO2009123623A1, has a Ki of <20 nM.

  • CAS Number: 1017931-53-1
  • MF: C19H21F6N3O
  • MW: 421.38
  • Catalog: Cathepsin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MSU-42011

MSU-42011 is an orally active retinoid X receptor (RXR) agonist. MSU-42011 inhibits the expression of iNOS and p-ERK protein. MSU-42011 has immunomodulatory and antitumor activity. MSU-42011 can be used for cancer research[1].

  • CAS Number: 2456434-36-7
  • MF: C24H34N2O2
  • MW: 382.54
  • Catalog: PERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Doxofylline

Doxofylline is an antagonist of adenosine A1 receptor which also inhibits phosphodiesterase IV.

  • CAS Number: 69975-86-6
  • MF: C11H14N4O4
  • MW: 266.253
  • Catalog: Adenosine Receptor
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 505.2±53.0 °C at 760 mmHg
  • Melting Point: 144-146ºC
  • Flash Point: 259.3±30.9 °C

Quizalofop-P

Quizalofop-P is absorbed through weed stems and leaves, conducts upward and downward in plants, accumulates at the top and intermediate meristems, inhibits cellular fatty acid synthesis, and makes weeds necrotic. Quizalofop-P is highly selective between grass weeds and dicotyledonous crops[1].

  • CAS Number: 94051-08-8
  • MF: C17H13ClN2O4
  • MW: 344.749
  • Catalog: Acetyl-CoA Carboxylase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 533.3±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 276.3±30.1 °C

4-Diethylaminobenzaldehyde

4-Diethylaminobenzaldehyde is a reversible aldehyde dehydrogenases (ALDHs) inhibitor, with a Ki of 4 nM for ALDH1. 4-Diethylaminobenzaldehyde displays potent anti-androgenic effect (IC50= 1.71μM)[1][2].

  • CAS Number: 120-21-8
  • MF: C11H15NO
  • MW: 177.243
  • Catalog: Aldehyde Dehydrogenase (ALDH)
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 329.6±0.0 °C at 760 mmHg
  • Melting Point: 37-41 °C(lit.)
  • Flash Point: 110.2±12.0 °C

Tetramisole hydrochloride

Tetramisole hydrochloride is an inhibitor of alkaline phosphatases, is a high purity antiparasitic.

  • CAS Number: 5086-74-8
  • MF: C11H13ClN2S
  • MW: 240.752
  • Catalog: Parasite
  • Density: N/A
  • Boiling Point: 344.4ºC at 760 mmHg
  • Melting Point: 266-267ºC
  • Flash Point: 162.1ºC

Swertiajaponin

Swertiajaponin is a tyrosinase inhibitor, forms multiple hydrogen bonds and hydrophobic interactions with the binding pocket of tyrosinase, with an IC50 of 43.47 μM. Swertiajaponin also inhibits oxidative stress-mediated MAPK/MITF signaling, leading to decrease in tyrosinase protein level. Swertiajaponin suppresses melanin accumulation and exhibits strong anti-oxidative activity[1].

  • CAS Number: 6980-25-2
  • MF: C22H22O11
  • MW: 462.404
  • Catalog: Tyrosinase
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 761.3±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 266.6±26.4 °C

FPFT-2216

FPFT-2216, a “molecular glue” compound, degrades phosphodiesterase 6D (PDE6D), zinc finger transcription factors Ikaros (IKZF1), Aiolos (IKZF3), and casein kinase 1α (CK1α). FPFT-2216 can be used for the research of cancer and inflammatory disease[1][2].

  • CAS Number: 2367619-87-0
  • MF: C12H12N4O3S
  • MW: 292.31
  • Catalog: Casein Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IDX184

IDX184 is a potent and orally bioavailable inhibitor of HCV replication. IDX184 potently inhibits HCV polymerase (IC50=0.31 μM, Ki=52.3 nM)[1][2].

  • CAS Number: 1036915-08-8
  • MF: C25H35N6O9PS
  • MW: 626.61900
  • Catalog: HCV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2α,19α-Dihydroxy-3-oxo-urs-12-en-28-oic acid

2α,19α-Dihydroxy-3-oxo-urs-12-en-28-oic acid, a natural ursane-type triterpene, is a potent inhibitor of HIV Protease (HIV Protease). 2α,19α-Dihydroxy-3-oxo-urs-12-en-28-oic acid is also an inhibitor of the activation of Epstein-Barr virus early antigen (EBV-EA). 2α,19α-Dihydroxy-3-oxo-urs-12-en-28-oic acid displays an inhibitory activity against nitric oxide production in Lipopolysaccharide (Lipopolysaccharides)-activated RAW 264.7 cells[1][2].

  • CAS Number: 176983-21-4
  • MF: C30H46O5
  • MW: 486.683
  • Catalog: HSV
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 616.9±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 340.9±28.0 °C

Schaftoside

Schaftoside is a flavonoid found in a variety of Chinese herbal medicines, such as Eleusine indica. Schaftoside inhibits the expression of TLR4 and Myd88. Schaftoside also decreases Drp1 expression and phosphorylation, and reduces mitochondrial fission[1].

  • CAS Number: 51938-32-0
  • MF: C26H28O14
  • MW: 564.49
  • Catalog: Dynamin
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: 1028.2±65.0 °C at 760 mmHg
  • Melting Point: 228ºC
  • Flash Point: 342.7±27.8 °C

IDO-IN-6

IDO-IN-6 (NLG-1486) is an indoleamine 2,3-dioxygenase (IDO) inhibitor extracted from patent WO WO2012142237A1, Compound 1486, has an IC50 of <1 μM.

  • CAS Number: 1402837-76-6
  • MF: C18H21FN2O2
  • MW: 316.370
  • Catalog: Indoleamine 2,3-Dioxygenase (IDO)
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 555.4±35.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 289.7±25.9 °C

MeOSuc-Ala-Ala-Pro-Met-AMC

MeOSuc-Ala-Ala-Pro-Met-AMC is a peptide substrate of elastases and chymotrypsin-like serine peptidases[1].

  • CAS Number: 201853-55-6
  • MF: C31H41N5O9S
  • MW: 659.750
  • Catalog: Elastase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 1033.2±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 578.6±34.3 °C