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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Rennin

Rennin, also known as Chymosin, is a pepsin-related proteolytic enzyme synthesized by cells in the stomach of certain animals that efficiently converts liquid milk into a semi-solid, allowing it to remain in the stomach for longer. The natural substrate of Rennin is K-casein, which is specifically cleaved at the peptide bond between amino acid residues 105 and 106, phenylalanine and methionine, and is widely used in cheese production[1].

  • CAS Number: 9001-98-3
  • MF: C7H6O4
  • MW: 154.120
  • Catalog: Ser/Thr Protease
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 513.7±50.0 °C at 760 mmHg
  • Melting Point: 225-227℃
  • Flash Point: 226.8±23.6 °C

ITI214 free base

ITI-214 (free base) is a picomolar PDE1 inhibitor with excellent selectivity against other PDE family members and against a panel of enzymes, receptors, transporters, and ion channels, exhibits potent PDE1 inhibitory activity (Ki = 58 pM).IC50 value: 58 pM (Ki)Target: PDE1in vitro: ITI-214 exhibits picomolar inhibitory potency for PDE1, demonstrates excellent selectivity against all other PDE families. ITI214 exhibits excellent selectivity over other PDE familymembers. For instance, the Ki values of ITI214 against recombinant full-length human PDE1A, PDE1B, and PDE1C are 33 pM, 380 pM, and 35 pM, respectively. ITI214 is profiled in a panel of enzymes, receptors, transporters, and ion channels from Caliper at 10 μM, which is over 170000 times higher than its Ki for PDE1, and demonstrates good selectivity. [1]in vivo: ITI214 possesses a good overall profile with balanced physicochemical properties, excellent potency and selectivity, and good pharmacokinetics. ITI214 is found to significantly enhance memory performance in the test with a minimum effective dose of 3 mg/kg. [1]

  • CAS Number: 1160521-50-5
  • MF: C29H26FN7O
  • MW: 507.561
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 731.7±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 396.3±35.7 °C

ZJ 43

ZJ43 is a potent NAAG peptidase inhibitor, with an IC50 of 2.4 nM and a Ki of 0.8 nM. ZJ43 sufficiently activates group II mGluR and reduces some of the behavioral effects of PCP. ZJ43 shows an analgesic effect in neuropathic and inflammatory and pain models[1].

  • CAS Number: 723331-20-2
  • MF: C12H20N2O7
  • MW: 304.30
  • Catalog: mGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

saxagliptin

Saxagliptin(BMS477118) is a selective and reversible DPP4 inhibitor with IC50 of 26 nM and Ki of 1.3 nM.IC50 value: 26 nM [1]Target: DPP4in vitro: Saxagliptin has an inhibition constant Ki of 1.3 nM for DPP4 inhibition, which is 10-fold more potent than either vildagliptin or sitagliptin (another two DPP4 inhibitors) with Ki of 13 and 18 nM. In addition, Saxagliptin demonstrates greater specificity for DPP4 than for either the DPP8 or DPP9 enzymes (400- and 75- fold, respectively). The active metablite of saxagliptin is two-fold less potent than the parent. Both Saxagliptin and its metabolite are highly selective (>4000-fold) for the prevention of DPP4 compared with a range of other proteases (selectivity of sitagliptin and vildagliptin for DPP4 is >2600 and <250-fold, respectively, compared with DPP8 and DPP9) [2]. Saxagliptin reduces the degradation of the incretin hormone glucagon-like peptide-1, thereby enhancing its actions, and is associated with improved β-cell function and suppression of glucagon secretion.in vivo: Saxagliptin is highly effective at eliciting marked dose-dependent enhancements in glucose clearance in the dose range 0.13-1.3 mg/kg in ob/ob mice relative to controls. Saxagliptin dose-dependently elevate plasma insulin significantly at 15 min post-oGTT, with concomitant improvement in the glucose clearance curves at 60 min post-oGTT [4].

  • CAS Number: 361442-04-8
  • MF: C18H25N3O2
  • MW: 315.410
  • Catalog: Dipeptidyl Peptidase
  • Density: 1.35
  • Boiling Point: 548.7±35.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 285.6±25.9 °C

SB-435495 hydrochloride

SB-435495 hydrochloride is a potent, selective, reversible, non-covalent and orally active Lp-PLA2 inhibitor with an IC50 of 0.06 nM[1][3].

  • CAS Number: 304694-41-5
  • MF: C38H41ClF4N6O2S
  • MW: 757.28
  • Catalog: Phospholipase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3,4-Secocucurbita-4,24-diene-3,26,29-trioic acid

(24E)-3,4-Secocucurbita-4,24-diene-3,26,29-trioic acid is a potent PTP1B inhibitor, with an IC50 of 0.4 μM. (24E)-3,4-Secocucurbita-4,24-diene-3,26,29-trioic acid exhibits potent PTP1B inhibitory activity without cytotoxicity[1].

  • CAS Number: 329975-47-5
  • MF: C31H48O6
  • MW: 516.71
  • Catalog: Phosphatase
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 669.2±20.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 372.5±18.3 °C

CP-544439

CP-544439 is a potent and orally active matrix metalloproteinase-13 (MMP-13) inhibitor with an IC50 of 0.75 nM[1][2].

  • CAS Number: 230954-09-3
  • MF: C18H19FN2O6S
  • MW: 410.41700
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HFI-419

HFI-419 is an insulin-regulated aminopeptidase (IRAP) inhibitor. HFI-419 has inhibitory potency for IRAP with Ki value of 0.48 μM. HFI-419 can be used for the research of cognitive and memory impairments such as Alzheimer's disease, brain trauma, and stroke[1].

  • CAS Number: 1110650-72-0
  • MF: C19H18N2O5
  • MW: 354.36
  • Catalog: Aminopeptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

hCAIX-IN-10

hCAIX-IN-10 (Compound 6i) is a selective carbonic anhydrase IX and XII inhibitor with Ki s of 61.5 and 586.8 nM for hCA IX and hCA XII, respectively.  hCA IX and hCA XII are transmembrane isoforms which have been characterized as biomarkers for several types of tumors. The hCA XII assists in maintenance of acid-base homoeostasis in normal as well as tumor cells[1].

  • CAS Number: 2497504-72-8
  • MF: C28H21N3O3S
  • MW: 479.55
  • Catalog: Carbonic Anhydrase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Leupeptin hemisulfate salt

Leupeptin hemisulfate is a reversible, competitive serine/cysteine protease inhibitor.

  • CAS Number: 103476-89-7
  • MF: C20H38N6O4.1/2H2SO4
  • MW: 475.59
  • Catalog: Peptides
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Febuxostat sodium

Febuxostat (TEI 6720) sodium is a potent, selective and non-purine xanthine oxidase (XO) inhibitor with a Ki value of 0.6 nM. Febuxostat sodium has the potential for the research of hyperuricemia and gout[1][2][3].

  • CAS Number: 1140907-13-6
  • MF: C16H15N2NaO3S
  • MW: 338.36
  • Catalog: Xanthine Oxidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Anacetrapib

Anacetrapib is a potent CETP inhibitor, with IC50s of 7.9±2.5 nM and 11.8±1.9 nM for rhCETP and C13S CETP mutant, respectively.

  • CAS Number: 875446-37-0
  • MF: C30H25F10NO3
  • MW: 637.508
  • Catalog: CETP
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 555.3±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 289.6±30.1 °C

Sorbinil

Sorbinil, is an Aldose reductase inhibitor (ARI).Sorbinil plays therapeutic role in treating diabetes and diabetic complications, decreases AR activity and inhibits polyol pathway, it to be found comparatively safer than other ARIs for human use[1].

  • CAS Number: 68367-52-2
  • MF: C11H9FN2O3
  • MW: 236.19900
  • Catalog: Aldose Reductase
  • Density: 1.52g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CDD3506

CDD3506 is used for elevating high density lipoprotein cholesterol (HDL) by inducing hepatic cytochrome P450IIIA (CYP3A) activity.

  • CAS Number: 197913-15-8
  • MF: C22H19N3
  • MW: 325.406
  • Catalog: Cytochrome P450
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 506.4±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 260.1±28.7 °C

TMP778

TMP778 is a potent and selevtive RORγt inverse agonist, with an IC50 of 7 nM in FRET assay.

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

H-Ile-Pro-Pro-OH

H-Ile-Pro-Pro-OH, a milk-derived peptide[1], inhibits angiotensin-converting enzyme (ACE)[1] with an IC50 of 5 μM[2]. Antihypertensive tripeptides[1].

  • CAS Number: 26001-32-1
  • MF: C16H27N3O4
  • MW: 325.40
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: 1.248 g/cm3
  • Boiling Point: 572.556ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 300.071ºC

CL67

CL67 is a potent hypoxia-inducible factor (HIF) pathway inhibitor. CL67 interferes G-quadruplex structures within promoter sequences. CL67 can be used in research of renal cancer[1].

  • CAS Number: 1401242-86-1
  • MF: C38H42N10O2
  • MW: 670.81
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PTP1B-IN-3

PTP1B-IN-3 is a potent and selective PTP1B inhibitor with IC50s of 120 nM (PTP1B) and 120 nM (TCPTP), respectively.

  • CAS Number: 809272-64-8
  • MF: C12H7BrF2NO3P
  • MW: 362.06300
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ZD-0892

ZD-0892 is a selective and potent inhibitor of a neutrophil elastase with Kis of 6.7 and 200 nM for human neutrophil elastase and porcine pancreatic elastase, respectively.

  • CAS Number: 171964-73-1
  • MF: C24H32F3N3O5
  • MW: 499.52
  • Catalog: Elastase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

cm-10-18

CM-10-18 is a potent inhibitor of ER α-glucosidase. CM-10-18 demonstrated superior in vitro antiviral activity against representative viruses from four viral families causing hemorrhagic fever. CM-10-18 efficiently protected the lethality of dengue virus infection of mice.

  • CAS Number: 1159614-57-9
  • MF: C17H35NO5
  • MW: 333.46
  • Catalog: Glucokinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-Desmethyl Apalutamide

N-Desmethyl Apalutamide is an active metabolite of Apalutamide. N-Desmethyl Apalutamide is a less potent antagonist of the androgen receptor and is responsible for one-third of the activity of Apalutamide. The formation of N-Desmethyl Apalutamide mediated predominantly by CYP2C8 and CYP3A4. N-Desmethyl Apalutamide is moderate to strong CYP3A4 and CYP2B6 inducer and has an excellent plasma-proteins bound concentration[1][2][3].

  • CAS Number: 1332391-11-3
  • MF: C20H13F4N5O2S
  • MW: 463.41
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sildenafil citrate-d8

Sildenafil (citrate)-d8 is the deuterium labeled Sildenafil citrate[1]. Sildenafil citrate is a potent phosphodiesterase type 5 (PDE5) inhibitor with IC50 of 5.22 nM.

  • CAS Number: 1215071-03-6
  • MF: C28H30D8N6O11S
  • MW: 674.75
  • Catalog: Bacterial
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HEC96719

HEC96719 is a selective and orally active tricyclic farnesoid X receptor (FXR) agonist with EC50 values of 1.37 and 1.55 nM by time-resolved fluorescence energy transfer (TR-FRET) and luciferase reporter assays, respectively. HEC96719 significantly improves non-alcoholic steatohepatitis (NASH) and liver fibrosis with favorable tissue distribution in liver and intestine. HEC96719 can be used for the research of non-alcoholic steatohepatitis[1].

  • CAS Number: 2181834-03-5
  • MF: C29H22Cl2N2O5
  • MW: 549.40
  • Catalog: FXR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AR453588

AR453588 is a potent and orally bioavailable anti-diabetic glucokinase activator, with an EC50 of 42 nM. AR453588 shows anti-hyperglycemic activity[1].

  • CAS Number: 1065609-00-8
  • MF: C25H25N7O2S2
  • MW: 519.64
  • Catalog: Glucokinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PKM2-IN-1

PKM2-IN-1 is a pyruvate kinase M2 (PKM2) inhibitor with an IC50 of 2.95 μM.

  • CAS Number: 94164-88-2
  • MF: C18H19NO2S2
  • MW: 345.48
  • Catalog: Pyruvate Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hippuryl-Phe-OH

Hippuryl-L-phenylalanine is a substrate of carboxypeptidase. Carboxypeptidase is a protease enzyme that related with obesity, epilepsy and neurodegeneration. Hippuryl-L-phenylalanine can be used for the determination of carboxypeptidase activity[1][2].

  • CAS Number: 744-59-2
  • MF: C18H18N2O4
  • MW: 326.346
  • Catalog: Carboxypeptidase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 673.3±55.0 °C at 760 mmHg
  • Melting Point: 140-144ºC
  • Flash Point: 361.0±31.5 °C

HB007

HB007 is a small ubiquitin-related modifier 1 (SUMO1) degrader. HB007 induces ubiquitination and degradation of SUMO1, resulting in reduced tumor growth in vivo. HB007 can be used for the research of brain, breast, colon, and lung cancers[1][2].

  • CAS Number: 2387821-46-5
  • MF: C15H9ClN4Os
  • MW: 328.78
  • Catalog: E1/E2/E3 Enzyme
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4-isopropoxybenzaldehyde

ALDH1A3-IN-3 (compound 16) is a potent inhibitor of ALDH1A3, with an IC50 of 0.26 μM. ALDH1A3-IN-3 is also a good ALDH3A1 substrate. ALDH1A3-IN-3 can be used for the research of prostate cancer[1].

  • CAS Number: 18962-05-5
  • MF: C10H12O2
  • MW: 164.20100
  • Catalog: Aldehyde Dehydrogenase (ALDH)
  • Density: 1.036
  • Boiling Point: 108-110 °C (5 mmHg)
  • Melting Point: N/A
  • Flash Point: 108-110°C/5mm

IDO1/2-IN-1

IDO1/2-IN-1 (compound 4t) is the first potent IDO1/IDO2 dual inhibitor with IC50s of 28 nM and 144 nM for IDO1 and IDO2, respectively. IDO1/2-IN-1 exhibits antitumor activies. Orally active[1].

  • CAS Number: 2310286-45-2
  • MF: C16H18BrFN8O4
  • MW: 485.27
  • Catalog: Indoleamine 2,3-Dioxygenase (IDO)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ecallantide

Ecallantide (DX-88) is a specific recombinant plasma kallikrein inhibitor. Ecallantide inhibits the production of bradykinin. Ecallantide can be used to prevent acute attacks of angioedema[1].

  • CAS Number: 460738-38-9
  • MF: C305H441N88O91S8
  • MW:
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A