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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FR221647

FR221647 is an orally active non-nucleoside inhibitor of adenosine deaminase. FR221647 is not cytotoxic at a concentration of 100 μM[1].

  • CAS Number: 256461-28-6
  • MF: C14H17N3O2
  • MW: 259.30
  • Catalog: Adenosine Deaminase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

hCAIX-IN-18

hCAIX-IN-18 (compound 30) is an inhibitor of carbonic anhydrase (CA), with Kis of 3.5 nM, 9.4 nM, 43.0 nM and 8.2 nM for hCAI, hCAII, hCAIX, hCAXII, respectively. hCAIX-IN-18 can be used for cancer research[1].

  • CAS Number: 2925261-76-1
  • MF: C17H19ClN4O3S
  • MW: 394.88
  • Catalog: Carbonic Anhydrase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Suc-Arg-Pro-Phe-His-Leu-Leu-Val-Tyr-AMC trifluoroacetate salt

Suc-Arg-Pro-Phe-His-Leu-Leu-Val-Tyr-AMC (Renin Substrate I) is a renin substrate[1]

  • CAS Number: 76524-84-0
  • MF: C66H88N14O14
  • MW: 1301.49000
  • Catalog: Renin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RA190

RA190, a bis-benzylidine piperidon, inhibits proteasome function by covalently binding to cysteine 88 of ubiquitin receptor RPN13.

  • CAS Number: 1617495-03-0
  • MF: C28H23Cl5N2O2
  • MW: 596.76
  • Catalog: Proteasome
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

hDHODH-IN-9

hDHODH-IN-9 (Compound 3k) is a potent inhibitor of hDHODH with an IC50 of 0.34 μM. hDHODH-IN-9 demonstrates high cytotoxic activity against MCF-7 and A375 cells and good selectivity. hDHODH-IN-9 has the potential for the research of cancer diseases[1].

  • CAS Number: 133676-47-8
  • MF: C21H21NO4
  • MW: 351.40
  • Catalog: Lactate Dehydrogenase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

rac-Sitagliptin

(Rac)-Sitagliptin is an isoform of Sitagliptin (HY-13749), which is a potent and orally active inhibitor of DPP4 with an IC50 of 19 nM in Caco-2 cell extracts[1].

  • CAS Number: 823817-56-7
  • MF: C16H15F6N5O
  • MW: 407.31
  • Catalog: Autophagy
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 529.9±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 274.3±32.9 °C

IDD388

IDD388 is a potent aldose reductase (ALR2 or AKR1B1) inhibitor with IC50 of 0.4 uM, shows weak inhibition for AKR1B10 (IC50=4.4 uM).

  • CAS Number: 314297-26-2
  • MF: C16H12BrClFNO4
  • MW: 416.627
  • Catalog: Aldose Reductase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Moexipril

Moexipril is an orally active and potent angiotensin-converting enzyme (ACE) inhibitor. Moexipril can readily penetrate lipid membranes and thus target plasma and tissue ACE. Moexipril may improve endothelial dysfunction and exert neuroprotective effects. Moexipril can used for cardiovascular disease research[1][2].

  • CAS Number: 103775-10-6
  • MF: C27H34N2O7
  • MW: 498.57
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 709.3±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 382.8±32.9 °C

PF 04937319

PF-04937319 is a glucokinase activator (GKA) with EC50 value of 154.4  μM, one of the most promising strategies for the treatment of type 2 diabetes mellitus[1].PF-04937319 is designed to maintain glucose-lowering efficacy while mitigating the risk of hypoglycaemia observed with many other GKAs[2].

  • CAS Number: 1245603-92-2
  • MF: C22H20N6O4
  • MW: 432.432
  • Catalog: Glucokinase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PYZD 4409

PYZD-4409 is a novel small molecule inhibitor of Ubiquitin-activating enzyme UBA1/E1 enzyme with an IC50 of 20 uM (cell-free enzymatic assay).IC50 Value: 20 uM (cell-free enzymatic assay) [1]Target: E1 enzyme (Ubiquitin-activating enzyme)in vitro: PYZD-4409 inhibited the ATP-dependent activation of ubiquitin and subsequent transfer of the activated ubiquitin from the E1 to the common human E2 enzyme UBE2E2 in a gel-based assay. The IC50 of inhibition was estimated to be 20μM in a cell-free enzymatic assay. Suggesting specificity of PYZD-4409 for the E1 enzyme, the compound had no effect on unrelated enzymes such as α-Mannosidase II glycosylation enzyme or Luciferase at concentrations up to 100μM (data not shown). It also did not inhibit the summo E1, Uba2, at concentrations up to 100μM. In 5 of 8 leukemia and myeloma cell lines, PYZD-4409 induced cell death with a LD50 less than 10μM. Myeloma cell lines were particularly sensitive to E1 inhibition because PYZD-4409 induced cell death with 3 of 4 myeloma cell lines (ie, LP1, KMS11, and U226) having an LD50 of 3μM or less. In contrast, solid tumor cell lines were less sensitive with an LD50 of approximately 15 to 20μM [1]. in vivo: SCID mice were injected subcutaneously with MDAY-D2 murine leukemia cells and then treated with PYZD-4409 (10 mg/kg) or buffer control intraperitoneally daily on alternate days over 8 days. Sixteen days after tumor implantation, the mice were killed, and the tumors excised and weighed. Compared with control-treated mice, treatment with PYZD-4409 delayed tumor growth and decreased tumor weight without untoward toxicity. Inhibition of the E1 can achieve an antitumor effect in vivo [1].

  • CAS Number: 423148-78-1
  • MF: C14H7ClFN3O5
  • MW: 351.67400
  • Catalog: E1/E2/E3 Enzyme
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

WWL 123

WWL123, a carbamate-based compound, is a potent and selective ABHD6 inhibitor. WWL123 can be used for research of inflammation, metabolic disorders (obesity and type II diabetes mellitus) and epilepsy[1].

  • CAS Number: 1338574-83-6
  • MF: C28H24N2O3
  • MW: 436.50
  • Catalog: MAGL
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 646.2±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 344.6±31.5 °C

fluazifop-P-butyl

Fluazifop-P-butyl, a graminicide from arylophenoxypropionate group, is a acetyl-CoA carboxylase (ACCase) inhibitor[1].

  • CAS Number: 79241-46-6
  • MF: C19H20F3NO4
  • MW: 383.362
  • Catalog: Acetyl-CoA Carboxylase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 436.0±45.0 °C at 760 mmHg
  • Melting Point: 5ºC
  • Flash Point: 217.5±28.7 °C

ML355

ML355 is a potent and selective inhibitors of 12-Lipoxygenase(12-LOX) with IC50 of 0.34 μM, excellent selectivity over related lipoxygenases and cyclooxygenases, and possess favorable ADME properties.IC50 value: 0.34 μM [1]Target: 12-LOXML355 inhibits PAR-4 induced aggregation and calcium mobilization in human platelets and reduce 12-HETE in β-cells.

  • CAS Number: 1532593-30-8
  • MF: C21H19N3O4S2
  • MW: 441.523
  • Catalog: 5-Lipoxygenase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 654.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 349.6±34.3 °C

Gac0001e5

GAC0001E5 is a novel LXR inverse agonist, functioning as LXR a degrader"

  • CAS Number: 929492-71-7
  • MF: C20H24N2O3
  • MW: 340.423
  • Catalog: LXR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-04929113(SNX-5422)

SNX-5422 (PF-04929113), a prodrug of SNX-2112, is an orally active Hsp90 inhibitor, with a Kd of 41 nM, and also induces Her-2 degradation, with an IC50 of 37 nM.

  • CAS Number: 908115-27-5
  • MF: C25H30F3N5O4
  • MW: 521.532
  • Catalog: HSP
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 646.5±55.0 °C at 760 mmHg
  • Melting Point: 298-299℃
  • Flash Point: 344.8±31.5 °C

Acetyl Podocarpic Acid Anhydride

Acetyl podocarpic acid anhydride is a potent, semisynthetic liver X receptor(LXR) agonist derived from extracts of the mayapple. Acetyl podocarpic acid anhydride has the potential to be useful for the prevention and treatment of atherosclerosis, especially in the context of low HDL levels[1].

  • CAS Number: 344327-48-6
  • MF: C38H46O7
  • MW: 614.768
  • Catalog: LXR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 695.5±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 284.6±31.5 °C

NF 1819

MGL-IN-1 is a potent and selective irreversible MGL (β-lactam-based monoacylglycerol lipase) inhibitor. MGL-IN-1 alleviates symptoms in a MS model in vivo and exhibits analgesic effects in an acute inflammatory pain model in vivo. MGL-IN-1 displays high membrane permeability and brain penetrant[1].

  • CAS Number: 1881244-28-5
  • MF: C24H22FN5O4
  • MW: 463.46
  • Catalog: MAGL
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 660.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 353.2±34.3 °C

RWJ 63556

RWJ 63556 is an orally active COX-2 selective/5-lipoxygenase inhibitor, with anti-inflammatory activities.

  • CAS Number: 190967-35-2
  • MF: C11H10FNO3S2
  • MW: 287.330
  • Catalog: 5-Lipoxygenase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 403.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 197.8±31.5 °C

Sivelestat sodium salt hydrate

Sivelestat(ONO5046; LY544349; EI546) is a competitive inhibitor of human neutrophil elastase(IC50 = 44 nM; Ki=200 nM); also inhibited leukocyte elastase obtained from rabbit, rat, hamster and mouse.IC50 value: 44 nM [1]Target: neutrophil elastaseONO-5046 did not inhibit trypsin, thrombin, plasmin, plasma kallikrein, pancreas kallikrein, chymotrypsin and cathepsin G even at 100 microM. In in vivo studies, ONO-5046 suppressed lung hemorrhage in hamster (ID50 = 82 micrograms/kg) by intratracheal administration and increase of skin capillary permeability in guinea pig (ID50 = 9.6 mg/kg) by intravenous administration, both of which were induced by human neutrophil elastase [1]. Sivelestat sodium hydrate is an anti-neutrophil elastase inhibitor and may be one of the treatment options for acute respiratory failure due to pneumocystis pneumonia in AIDS patients [2].

  • CAS Number: 127373-66-4
  • MF: C20H22N2O7S
  • MW: 434.463
  • Catalog: Elastase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BMT-297376

BMT-297376, the optimized Linrodostat, is a potent IDO1 inhibitor[1].

  • CAS Number: 2251031-81-7
  • MF: C23H29F2N3O3
  • MW: 433.49
  • Catalog: Indoleamine 2,3-Dioxygenase (IDO)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Glutaryl-Gly-Arg-AMC hydrochloride salt

Glutaryl-Gly-Arg-AMC is a peptide substrate of urokinase plasminogen activator (uPA)[1].

  • CAS Number: 65147-16-2
  • MF: C10H14ClN
  • MW: 183.67800
  • Catalog: PAI-1
  • Density: 1.45g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MMP-2/9-IN-1

MMP-2/9-IN-1 (Compound 4a) is a potent dual MMP-2 and MMP-9 inhibitor with IC50 values of 56 nM and 38 nM, respectively. MMP-2/9-IN-1 inhibits tumor growth, strongly induces cancer cell apoptosis, inhibits cell migration, and suppresses cell cycle progression leading to DNA fragmentation[1].

  • CAS Number: 2415311-84-9
  • MF: C14H16IN7S
  • MW: 441.29
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Simvastatin acid calcium hydrate

Simvastatin acid (Tenivastatin) calcium hydrate is a potent HMG-CoA reductase (HMGCR) inhibitor. Simvastatin acid calcium hydrate reduces Indoxyl sulfate-mediated reactive oxygen species (ROS) production in human cardiomyocytes. Simvastatin acid calcium hydrate can also modulates OATP3A1 expression in cardiomyocytes and HEK293 cells transfected with the OATP3A1 gene[1][2].

  • CAS Number: 530112-57-3
  • MF: C50H84CaO15
  • MW: 965.27100
  • Catalog: HMG-CoA Reductase (HMGCR)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dorzagliatin

Dorzagliatin (HMS5552), a dual-acting glucokinase (GK) activator, improves glycaemic control and pancreatic β-cell function in type 2 diabetes[1].

  • CAS Number: 1191995-00-2
  • MF: C22H27ClN4O5
  • MW: 462.927
  • Catalog: Glucokinase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 761.7±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 414.5±32.9 °C

Roxadustat-d5

Roxadustat-d5 is deuterium labeled Roxadustat. Roxadustat is an oral hypoxia-inducible factor prolyl-hydroxylase inhibitor (HIF-PHI) that promotes erythropoiesis through increasing endogenous erythropoietin, improving iron regulation, and reducing hepcidin[1].

  • CAS Number: 2043026-13-5
  • MF: C19H11D5N2O5
  • MW: 357.37
  • Catalog: Ferroptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-Ketoglutaric acid-d6

2-Ketoglutaric acid-d6 is the deuterium labeled 2-Ketoglutaric acid[1]. 2-Ketoglutaric acid (Alpha-Ketoglutaric acid) is an intermediate in the production of ATP or GTP in the Krebs cycle. 2-Ketoglutaric acid also acts as the major carbon skeleton for nitrogen-assimilatory reactions. 2-Ketoglutaric acid is a reversible inhibitor of tyrosinase (IC50=15 mM)[2].

  • CAS Number: 1173021-86-7
  • MF: C5D6O5
  • MW: 152.13500
  • Catalog: Tyrosinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FASN-IN-2

FASN-IN-2 is a Fatty Acid Synthase (FASN) inhibitor extracted from patent WO2012122391A1, compound 152, has an IC50 of 0.052 μM and an EC50 of 0.072 μM[1].

  • CAS Number: 1399177-37-7
  • MF: C27H29N5O
  • MW: 439.55
  • Catalog: Fatty Acid Synthase (FAS)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BVT 948

BVT948 is a protein tyrosine phosphatase (PTP) inhibitor which can also inhibit several cytochrome P450 (P450) isoforms and lysine methyltransferase SETD8.

  • CAS Number: 39674-97-0
  • MF: C14H11NO3
  • MW: 241.24200
  • Catalog: Histone Methyltransferase
  • Density: 1.39g/cm3
  • Boiling Point: 400.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 196.2ºC

Nampt activator-3

NAMPT activator-3, a NAT derivative, is a NAMPT activator with an EC50 of 2.6 μM and a KD of 132 nM. NAMPT activator-3 effectively protects cultured cells from FK866 (HY-50876)-mediated toxicity. NAMPT activator-3 exhibits strong neuroprotective efficacy in a chemotherapy-induced peripheral neuropathy (CIPN) mouse model without any overt toxicity[1].

  • CAS Number: 2790481-63-7
  • MF: C19H20N2O3
  • MW: 324.37
  • Catalog: Nampt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cathepsin K inhibitor 2

Cathepsin K inhibitor 2 is a potent inhibitor of cathepsin K. Cathepsin K, Cat K is a cysteine protease expressed under the control of CTSK gene and closely related to osteoporosis, whose main function is to hydrolyze collagen. Cathepsin K inhibitor 2 has the potential for the research of osteoarthfitis (extracted from patent WO2021147882A1, compound 78)[1].

  • CAS Number: 2672478-52-1
  • MF: C30H33F4N5O3
  • MW: 587.61
  • Catalog: Cathepsin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A