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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LEI-401

LEI-401 is a first-in-class, selective, and CNS-active NAPE-PLD (N-acylphosphatidylethanolamine phospholipase D) inhibitor, with an IC50 of 27 nM. LEI-401 modulates emotional behavior in mice[1].

  • CAS Number: 2393840-15-6
  • MF: C24H31N5O2
  • MW: 421.54
  • Catalog: Phospholipase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Abiraterone N-oxide

Abiraterone N-oxide is a metabolite of Abiraterone (HY-148377). Abiraterone is a potent and irreversible CYP17A1 inhibitor with antiandrogen activity[1].

  • CAS Number: 2378463-76-2
  • MF: C24H31NO2
  • MW: 365.51
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CKI-7

CKI-7 is a potent and ATP-competitive casein kinase 1 (CK1) inhibitor with an IC50 of 6 μM and a Ki of 8.5 μM. CKI-7 is a selective Cdc7 kinase inhibitor. CKI-7 also inhibits SGK, ribosomal S6 kinase-1 (S6K1) and mitogen- and stress-activated protein kinase-1 (MSK1). CKI-7 has a much weaker effect on casein kinase II and other protein kinases[1][2][3][4].

  • CAS Number: 120615-25-0
  • MF: C11H12ClN3O2S
  • MW: 285.75000
  • Catalog: Casein Kinase
  • Density: 1.432g/cm3
  • Boiling Point: 499.7ºC at 760mmHg
  • Melting Point: 188-190ºC
  • Flash Point: 256ºC

Dagrocorat hydrochloride

Dagrocorat (PF-00251802) hydrochloride is an orally active and selective high-affinity partial agonist of the glucocorticoid receptor. Dagrocorat hydrochloride is also a time-dependent reversible inhibitor of CYP3A (IC50=1.3 μM in human liver microsomes) and CYP2D6 (Ki=0.57 μM in human liver microsomes). Dagrocorat hydrochloride can be used for the research of rheumatoid arthritis[1].

  • CAS Number: 1044535-61-6
  • MF: C29H30ClF3N2O2
  • MW: 531.01
  • Catalog: Glucocorticoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Carbonic anhydrase inhibitor 13

Carbonic anhydrase inhibitor 13 (compound 7) is a potent carbonic anhydrase (CA) inhibitor, which features 3-methylthiazolo[3,2-a]benzimidazole moiety (as a tail) connected to the zinc anchoring benzenesulfonamide moiety via ureido linker[1].

  • CAS Number: 2488872-31-5
  • MF: C17H15N5O3S2
  • MW: 401.46
  • Catalog: Carbonic Anhydrase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Amprenavir

Amprenavir (Agenerase) is a HIV protease inhibitor(Ki=0.6 nM) used to treat HIV infection.IC50 Value: 0.6 nM (Ki); Against wild-type clinical HIV isolates:14.6 +/- 12.5 ng/mL (mean +/- SD) [1].Target: HIV proteasein vitro: Amprenavir has an enzyme inhibition constant (Ki = 0.6 nM) that falls within the Ki range of the other protease inhibitors. Amprenavir's in vitro 50% inhibitory concentration (IC50) against wild-type clinical HIV isolates is 14.6 +/- 12.5 ng/mL (mean +/- SD) [1]. Amprenavir had direct inhibitory effects on invasion of Huh-7 hepatocarcinoma cell lines, inhibiting MMP proteolytic activation [2].in vivo: Amprenavir was able to promote regression of hepatocarcinoma growth in vivo by anti-angiogenetic and overall anti-tumor activities, independently by PI3K/AKT related pathways that at today is one of the more suggestive hypothesis to explain the anti-tumor effects of the different protease inhibitors [2]. Amprenavir efficiently activated PXR and induced PXR target gene expression in vitro and in vivo. Short-term exposure to amprenavirsignificantly increased plasma total cholesterol and atherogenic low-density lipoprotein cholesterol levels in wild-type mice, but not in PXR-deficient mice [3]. Amprenavir has been approved for adults and children; the recommended capsule doses are 1200 mg twice daily for adults and 20 mg/kg twice daily or 15 mg/kg 3 times daily for children < 13 years of age or adolescents < 50 kg [1].Clinical trial: A Study to Compare Three Doses of T-20 When Given in Combination With Abacavir, Amprenavir, Ritonavir, and Efavirenz to HIV-Infected Adults. Phase 2

  • CAS Number: 161814-49-9
  • MF: C25H35N3O6S
  • MW: 505.627
  • Catalog: HIV
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 722.5±70.0 °C at 760 mmHg
  • Melting Point: 72-74ºC
  • Flash Point: 390.8±35.7 °C

FG-2216

FG-2216 is a potent HIF-prolyl hydroxylase inhibitor with IC50 of 3.9 uM for PDH2 enzyme; orally bioavailable and induced significant and reversible Epo induction in vivo.IC50 value: 3.9 uM [1]Target: PDH inhibitorFG-2216 was orally bioavailable and induced significant and reversible Epo induction in vivo (82- to 309-fold at 60 mg/kg). Chronic oral dosing in male rhesus macaques was well tolerated, significantly increased erythropoiesis, and prevented anemia induced by weekly phlebotomy. Furthermore, modest increases in HbF-containing red cells and reticulocytes were demonstrated by flow cytometry, though significant increases in HbF were not demonstrated by high-pressure liquid chromatography (HPLC) [2].

  • CAS Number: 223387-75-5
  • MF: C12H9ClN2O4
  • MW: 280.66400
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cecropin B

Cecropin B has high level of antimicrobial activity and is considered as a valuable peptide antibiotic. Sequence: Lys-Trp-Lys-Val-Phe-Lys-Lys-Ile-Glu-Lys-Met-Gly-Arg-Asn-Ile-Arg-Asn-Gly-Ile-Val-Lys-Ala-Gly-Pro-Ala-Ile-Ala-Val-Leu-Gly-Glu-Ala-Lys-Ala-Leu-NH2.

  • CAS Number: 80451-05-4
  • MF: C176H302N52O41S
  • MW: 3834.67
  • Catalog: Peptides
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DT-061

DT-061 is an orally bioavailable activator of protein phosphatase 2A (PP2A) and could be applied in the therapy of KRAS-mutant and MYC-driven tumorigenesis[1].

  • CAS Number: 1809427-19-7
  • MF: C25H23F3N2O5S
  • MW: 520.52
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MY10

MY10 is a small-molecule inhibitor of RPTPβ/ζ (PTPRZ1) with IC50 of 0.1 uM, significantly increases the phosphorylation of key tyrosine residues of RPTPβ/ζ substrates involved in neuronal survival and differentiation; blocks ethanol conditioned place preference, shows limited effects on ethanol-induced ataxia, and potentiates the sedative effects of ethanol in mice; increases levels of phosphorylated ALK and TrkA in neuroblastoma cells, modulates signaling pathways activated by alcohol.

  • CAS Number: 2204270-73-3
  • MF: C15H10F6OS2
  • MW: 384.354
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Palmitic acid-d2-1

Palmitic acid-d2-1 is the deuterium 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: 62690-28-2
  • MF: C16H30D2O2
  • MW: 258.43600
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AZD-7295

AZD-7295 is a HCV NS5A protein inhibitor, with an EC50 of 7 nM for GT-1b replicon[1][2].

  • CAS Number: 929890-64-2
  • MF: C32H35F3N4O5S
  • MW: 644.70
  • Catalog: HCV Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NAcM-OPT

NAcM-OPT is an orally bioavailable cullin neddylation 1 (DCN1) inhibitor, which potently inhibits the DCN1-UBE2M interaction[1].

  • CAS Number: 2089293-61-6
  • MF: C23H29Cl2N3O
  • MW: 434.40
  • Catalog: NEDD8-activating Enzyme
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BMS-764459

BMS-764459 is a CRF1 antagonist. BMS-764459 can be used for the research of neurological disorders such as depression and anxiety. BMS-764459 is also an atypical CYP1A1 inducer[1][2].

  • CAS Number: 1188407-45-5
  • MF: C19H21F2N5O3
  • MW: 405.39900
  • Catalog: CRFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PDE5-IN-2

PDE5-IN-2 is a potent, highly selective, and orally active PDE5 inhibitor, with an IC50 of 0.31 nM, less potently inhibits PDE2A, PDE10A, PDE4D2, and PDE6C, with IC50s of 106, 46, 43, 1.2 nM, respectively. Anti-pulmonary arterial hypertension activity[1].

  • CAS Number: 2244517-61-9
  • MF: C25H21N3O6S
  • MW: 491.52
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TP0463518

TP0463518 is a potent hypoxia-inducible factor prolyl hydroxylases (PHDs) inhibitor with a Ki value of 5.3 nM for human PHD2. TP0463518 also inhibits human PHD1/PHD3 with IC50s of 18 and 63 nM as well as monkey PHD2 with an IC50 value of 22 nM[1].

  • CAS Number: 1558021-37-6
  • MF: C20H18ClN3O6
  • MW: 431.83
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mca-Arg-Pro-Lys-Pro-Tyr-Ala-Nva-Trp-Met-Lys(Dnp)-NH2 trifluoroacetate salt

Mca-Arg-Pro-Lys-Pro-Tyr-Ala-Nva-Trp-Met-Lys(Dnp)-NH2 is a biological active peptide. (MMP substrate)

  • CAS Number: 158584-08-8
  • MF: C79H105N19O19S
  • MW: 1656.86
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Carfilzomib-d8

Carfilzomib-d8 is deuterium labeled Carfilzomib. Carfilzomib (PR-171) is an irreversible proteasome inhibitor with an IC50 of 5 nM in ANBL-6 and RPMI 8226 cells.

  • CAS Number: 1537187-53-3
  • MF: C40H49D8N5O7
  • MW: 727.96
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 975.6±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 543.8±34.3 °C

Apixaban

Apixaban is a highly selective, reversible inhibitor of Factor Xa with Ki of 0.08 nM and 0.17 nM in human and rabbit, respectively.

  • CAS Number: 503612-47-3
  • MF: C25H25N5O4
  • MW: 459.497
  • Catalog: Factor Xa
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 770.5±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 419.8±32.9 °C

AT13387

Onalespib (AT13387) is a potent inhibitor of Hsp90, with a Kd of 0.71 nM.

  • CAS Number: 912999-49-6
  • MF: C24H31N3O3
  • MW: 409.521
  • Catalog: HSP
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 605.7±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 320.1±31.5 °C

FABP-IN-2

FABP-IN-2 is a novel FABP3 ligand. FABP-IN-2 inhibits FABP3/FABP4 with an IC50 of 1.16 μM and 4.27 μM respectively[1].

  • CAS Number: 1426533-99-4
  • MF: C25H21ClN2O3
  • MW: 432.90
  • Catalog: FABP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IOX2 sodium

IOX2 sodium is a specific prolyl hydroxylase-2 (PHD2) inhibitor with IC50 of 22 nM. IOX2 sodium regulates platelet function and arterial thrombosis by upregulating HIF-1α expression and inhibiting ROS production. IOX2 sodium can be used in the study of thrombotic diseases[1][2].

  • CAS Number: 2377239-85-3
  • MF: C19H15N2NaO5
  • MW: 374.32
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IDH1 Inhibitor 7

IDH1 Inhibitor 7 (Compound 88) is an IDH1 inhibitor with an IC50 of less than 100 nM[1].

  • CAS Number: 2135309-56-5
  • MF: C22H24F3N7O
  • MW: 459.47
  • Catalog: Isocitrate Dehydrogenase (IDH)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MMP-8/MMP-26 Fluorogenic Substrate

Dnp-PLAYWAR is a fluorogenic substrate for matrix metalloproteinase-8 (MMP-8) and MMP-26.The activity of MMP-8 and MMP-26 can be quantified by measuring tryptophan fluorescence that is unquenched upon peptide hydrolysis that removes the N-terminal dinitro

  • CAS Number: 135662-05-4
  • MF: C49H63N13O13
  • MW: 1042.1
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dim16

Dim16 is a dual PCSK9/HMG-CoAR inhibitor, with an IC50 value of 19 nM for PCSK9. Dim16 inhibits PCSK9-LDLR binding with an IC50 value of 0.8 nM. Dim16 increases LDL uptake in HepG2 cells[1].

  • CAS Number: 2743448-32-8
  • MF: C29H38IN5
  • MW: 583.55
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tetrahydrocurcumin D6

Tetrahydrocurcumin D6 (HZIV 81-2 D6) is a deuterium labeled Tetrahydrocurcumin. Tetrahydrocurcumin is a Curcuminoid which displays inhibitory activity for CYP2C9 and CYP3A4[1].

  • CAS Number: 1794898-13-7
  • MF: C21H18D6O6
  • MW: 378.45
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

WH-15

WH-15 is a fluorogenic PLC reporter with Km value of 49; 30, 86.1 µM for PLC-γ1, PLC-δ1, PLC-β2, respectively. WH-15 can be cleaved in a cascade reaction to generate fluorescent 6-aminoquinoline. WH-15 can be used to respond to imaging PLC activity in live cells[1].

  • CAS Number: 1264748-47-1
  • MF: C31H43N2O18P3
  • MW: 824.60
  • Catalog: Phospholipase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Isocitrate dehydrogenase

Isocitrate dehydrogenase (ICDH) is a citric acid or tricarboxylic acid cycle enzyme, is often used in biochemical studies. Isocitrate dehydrogenase catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate and reduces NAD(P)+ to NAD(P)H, it plays important roles in cellular metabolism[1].

  • CAS Number: 9028-48-2
  • MF:
  • MW:
  • Catalog: Isocitrate Dehydrogenase (IDH)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

hydrocotarnine

Hydrocotarnine is a Cbl inhibitor, and results in inflammasome-mediated IL-18 secretion in colitis. Hydrocotarnine increases expression of GLUT1 and cellular glucose uptake in glycolytic metabolism. Hydrocotarnine acts as an agent that provides analgesic effect in cancer research[1][2][3].

  • CAS Number: 550-10-7
  • MF: C12H15NO3
  • MW: 221.25200
  • Catalog: E1/E2/E3 Enzyme
  • Density: N/A
  • Boiling Point: 342.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 106.7ºC

Tipranavir

Tipranavir inhibits the enzymatic activity and dimerization of HIV-1 protease, exerts potent activity against multi-protease inhibitor (PI)-resistant HIV-1 isolates with IC50s of 66-410 nM.

  • CAS Number: 174484-41-4
  • MF: C31H33F3N2O5S
  • MW: 602.66400
  • Catalog: HIV
  • Density: 1.313g/cm3
  • Boiling Point: 680ºC at 760mmHg
  • Melting Point: 86-89ºC
  • Flash Point: 365.1ºC