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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N-Acetyl-3-acetoxy-5-phenylpyrrole

APPA is an aldose reductase inhibitor. APPA can effectively prevent apoptosis and the symptoms of Streptozotocin (HY-13753)-induced diabetes by inhibiting the polyol pathway in rats. APPA has the potential for diabetic nephropathy (DN) research[1].

  • CAS Number: 100750-39-8
  • MF: C14H13NO3
  • MW: 243.25800
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-(4-Chlorophenyl)acrylic acid

4-Chlorocinnamic acid has inhibitory effects on tyrosinase. 4-Chlorocinnamic acid has antibacterial activity. 4-Chlorocinnamic acid also inhibits Colletotrichum gloeosporioides growth[1][2][3].

  • CAS Number: 1615-02-7
  • MF: C9H7ClO2
  • MW: 182.60
  • Catalog: Bacterial
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 325.3±17.0 °C at 760 mmHg
  • Melting Point: 248-250 °C(lit.)
  • Flash Point: 150.5±20.9 °C

Kallikrein-IN-2

Kallikrein-IN-2 (compound 1) is a Kallikrein inhibitor[1].

  • CAS Number: 2702983-84-2
  • MF: C28H25F3N4O4
  • MW: 538.52
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-(Pyridin-3-yl)-N-(thiophen-2-ylmethyl)quinazolin-4-amine

PDE5-IN-9 (Compound 59) is a PDE5 inhibitor (IC50: 11.2 μM). PDE5-IN-9 shows interaction with Gln 817, Tyr 612, and Ala 767 amino acid residues. PDE5-IN-9 can be used for research of cardiovascular disease[1].

  • CAS Number: 157862-84-5
  • MF: C18H14N4S
  • MW: 318.40
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Varespladib

LY315920 (Varespladib) is a potent and selective human non-pancreatic secretory phospholipase A2 (sPLA) inhibitor with IC50 of 7 nM.IC50 value: 7 nMTarget: sPLA2in vitro: LY315920 exhibits the significant inhibitory effect on sPLA2 activity in serum from various species including rat, rabbit, guinea pig and human with IC50 of 8.1 nM, 5.0 nM, 3.2 nM and 6.2 nM, respectively. [2] In BAL cells challenged with human sPLA2, LY315920 at doses ranging from 0.1 μM–3 μM reduces the formation of thromboxane mediated by human sPLA2 in a concentration-dependent manner with an IC50 of approximately 0.8 μM. [2] In human conjunctival epithelial cell line (HCjE), LY315920 (10 μM) significantly inhibits all-trans-retinoic acid (RA) -induced membrane-associated mucin MUC16 expression by 100% at 24 hours and 99% at 48 hours. [3]in vivo: Ex vivo, LY315920 at doses ranging from 3 mg/kg to 30 mg/kg via i.v. inhibits human sPLA2-induced release of thromboxane from guinea pig BAL cells with ED50 of 16.1 mg/kg. [2] In Transgenic Mice Expressing Human sPLA2, both oral and i.v. administration of LY315920 (0.3 mg/kg–3 mg/kg) abolishes serum sPLA2 activity in a dose and time dependent manner. [2]

  • CAS Number: 172732-68-2
  • MF: C21H20N2O5
  • MW: 380.394
  • Catalog: Phospholipase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 667.9±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 357.7±34.3 °C

4,4'-[1,5-pentanediylbis(oxy)]bisbenzenecarboxamidine dimethylsulphonate

Pentamidine (MP-601205) dimesylate is an antimicrobial agent and interferes with DNA biosynthetics. Pentamidine dimesylate inhibits parasite Leishmania infantum with an IC50 of 2.5 μM. Pentamidine dimesylate is a potent and selective protein tyrosine phosphatases (PTPases) and phosphatase of regenerating liver (PRL) inhibitor. Pentamidine dimesylate has the potential for Gambian trypanosomiasis, antimony-resistant leishmaniasis, and Pneumocystis carinii pneumonia treatment. Antitumor and antibacterial activities[1][2][3][4].

  • CAS Number: 6823-79-6
  • MF: C20H28N4O5S
  • MW: 436.52500
  • Catalog: Bacterial
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SPK-601

SPK-601(LMV-601) is a potent phosphatidylcholine-specific phospholipase C (PC-PLC) inhibitor; SPK-601 is useful antimicrobial agent.IC50 value:Target: PC-PLC

  • CAS Number: 1096687-52-3
  • MF: C11H15KOS2
  • MW: 266.46500
  • Catalog: Phospholipase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mutant IDH1-IN-2

Mutant IDH1-IN-2 is a inhibitor of mutant Isocitrate dehydrogenase (IDH) proteins, with IC50 of in LS-MS biochemical assay, IC50 of 16.6 nM in Fluorescence biochemical assay.Target: Mutant IDH1Mutant IDH1-IN-2 has a neomorphic activity and in the treatment of diseases or disorders associated with such mutant IDH proteins including, but not limited to, cell-proliferation disorders, such as cancer. More bioactivity information in Patent WO 2013046136A1 (Example 224).

  • CAS Number: 1429176-69-1
  • MF: C24H31F2N5O2
  • MW: 459.532
  • Catalog: Isocitrate Dehydrogenase (IDH)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 578.1±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 303.4±32.9 °C

GCN2-IN-1

GCN2-IN-1 is a potent general control nonderepressible 2 kinase (GCN2) inhibitor with IC50s of <0.3 μM in the enzyme and cell assay.

  • CAS Number: 1448693-69-3
  • MF: C19H18N10O
  • MW: 402.413
  • Catalog: Ser/Thr Protease
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 760.0±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 413.4±35.7 °C

Methanone, 6-quinolinyl[(7S)-2,4,5,7-tetrahydro-2,7-dimethyl-3-(3,4,5-trifluorophenyl)-6H-pyrazolo[3,4-c]pyridin-6-yl]-

MAGL-IN-6 is a potent MAGL inhibitor with an IC50 of 4.71 nM. MAGL-IN-6 can be used for neurological disorders research (WO2020065613A1; example 234)[1].

  • CAS Number: 2414320-29-7
  • MF: C24H19F3N4O
  • MW: 436.43
  • Catalog: MAGL
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Topiramate D12

Topiramate D12 (McN 4853 D12) is a deuterium labeled Topiramate. Topiramate is a broad-spectrum antiepileptic agent. Topiramate is a GluR5 receptor antagonist. Topiramate produces its antiepileptic effects through enhancement of GABAergic activity, inhibition of kainate/AMPA receptors, inhibition of voltage-sensitive sodium and calcium channels, increases in potassium conductance, and inhibition of carbonic anhydrase[1][2][3].

  • CAS Number: 1279037-95-4
  • MF: C12H9D12NO8S
  • MW: 351.436
  • Catalog: Calcium Channel
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 438.7±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 219.1±31.5 °C

SCD1 inhibitor-1

SCD1 inhibitor-1 is a potent and liver-selective stearoyl-CoA desaturase-1 (SCD1) inhibitor[1].

  • CAS Number: 1069094-65-0
  • MF: C21H22N3NaO3S2
  • MW: 451.54
  • Catalog: Stearoyl-CoA Desaturase (SCD)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cyclosporin A-d3

Cyclosporin A-d3 is the d3-labeled Cyclosporin A (HY-B0579)[1].

  • CAS Number: 222295-76-3
  • MF: C62H108D3N11O12
  • MW: 1205.63
  • Catalog: Complement System
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Filibuvir

Filibuvir is a potent, selective non-nucleoside inhibitor (NNI) of the HCV nonstructural 5B protein (NS5B) RNA-dependent RNA polymerase, and it binds noncovalently in the “Thumb 2” pocket of NS5B. In vitro, filibuvir is equipotent against genotype 1a and 1b replicons, with an EC50 of 59 nM[1].

  • CAS Number: 877130-28-4
  • MF: C29H37N5O3
  • MW: 503.63600
  • Catalog: HCV Protease
  • Density: 1.29g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Z-LLF-CHO

Z-LLF-CHO (Z-Leu-Leu-Phe-CHO) is a potent inhibitor of the chymotrypsin-like activity of the pituitary multicatalytic proteinase complex (Ki = 460 nM). Z-LLF-CHO is also a NF-κB nuclear translocation inhibitor[1][2].

  • CAS Number: 133429-58-0
  • MF: C29H39N3O5
  • MW: 509.64
  • Catalog: Proteasome
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MK-0822

L-873724 is a potent, orally bioavailable, selective and reversible[2] non-basic cathepsin K inhibitor, with IC50s of 0.2, 178, 264, and 5239 nM for cathepsin K, cathepsin S, cathepsin L, cathepsin B, respectively[1]. L-873724 also exhibits an IC50 of 0.5 nM for rabbit cathepsin K. L-873724 inhibits bone resorption[2].

  • CAS Number: 603139-12-4
  • MF: C23H26F3N3O3S
  • MW: 481.53100
  • Catalog: Cathepsin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RORγt modulator 2

RORγt modulator 2 (Compound 21) is a modulator of retinoid-related orphan receptor γt (RORγt) with the IC50 of <50 nM. RORγt modulator 2 can be used for the research of RORyt mediated diseases such as, e.g., pain, inflammation, COPD, asthma, rheumatoid arthritis, colitis, multiple sclerosis, psoriasis, neurodegenerative diseases and cancer[1].

  • CAS Number: 2247083-47-0
  • MF: C28H29ClN2O4S
  • MW: 525.06
  • Catalog: ROR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

phosphoramidon

Phosphoramidon, a microbial metabolite, is a specific metalloprotease thermolysin inhibitor with an IC50 of 0.4 μg/mL. Phosphoramidon also inhibits endothelin-converting enzyme (ECE), neutral endopeptidase (NEP), and angiotensin-converting enzyme (ACE) with IC50 values of 3.5, 0.034, and 78 μM, respectively[1][2][3].

  • CAS Number: 36357-77-4
  • MF: C23H34N3O10P
  • MW: 543.50400
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: 1.48 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ML252

ML252 is a selective inhibitor of potassium channel, targeting to KCNQ2 channel (Kv7.2) (IC50=69 nM). ML252 also inhibits Cytochrome P450 with IC50s of 6.1 nM (CYP1A2), 18.9 nM (CYP2C9), 3.9 nM (CYP3A4), 19.9 nM (CYP2D6), respectively[1][2].

  • CAS Number: 1392494-64-2
  • MF: C20H24N2O
  • MW: 308.41700
  • Catalog: Potassium Channel
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

h-NTPDase-IN-2

h-NTPDase-IN-2 (compound 3l) is a pan-inhibitor of h-NTPDase, with IC50s of 0.35 μM (h-NTPDase1), 4.81 μM (h-NTPDase2), 37.73 μM (h-NTPDase3), 10.32 μM (h-NTPDase8), respectively[1].

  • CAS Number: 2939933-03-4
  • MF: C19H16N4S
  • MW: 332.42
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4-nitrocatechol

4-Nitrocatechol is a potent lipoxygenase inhibitor[1].

  • CAS Number: 3316-09-4
  • MF: C6H5NO4
  • MW: 155.108
  • Catalog: 5-Lipoxygenase
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 358.2±32.0 °C at 760 mmHg
  • Melting Point: 173-177 °C(lit.)
  • Flash Point: 168.8±13.6 °C

Ro 41-5253

Ro 41-5253 is an orally active selective retinoic acid receptor alpha (RARα) antagonist. Ro 41-5253 can bind RARα without inducing transcription or affecting RAR/RXR heterodimerization and DNA binding. Ro 41-5253 can inhibit cancer cell proliferation and induce apoptosis, has antitumor activity[1][2].

  • CAS Number: 144092-31-9
  • MF: C28H36O5S
  • MW: 484.64700
  • Catalog: Apoptosis
  • Density: 1.154g/cm3
  • Boiling Point: 661.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 353.8ºC

MK-0952

MK-0952 is a selective and orally active PDE4 inhibitor, with an IC50 of 0.53 nM. MK-0952 has the potential for Alzheimer’s disease study[1][2].

  • CAS Number: 934995-87-6
  • MF: C28H22FN3O4
  • MW: 483.49000
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ML298

ML298 is a potent, selective phospholipase PLD2 inhibitor with IC50 of 355 nM, displays >53-fold selectivity over PLD1 (IC50>20 uM); decreases invasive migration in U87-MG glioblastoma cells; has an attractive DMPK profile, making it an attractive tool compound to further dissect PLD2 function in multiple cellular and in vivo environments.

  • CAS Number: 1426916-02-0
  • MF: C22H23F3N4O2
  • MW: 432.439
  • Catalog: Phospholipase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 650.5±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 347.2±31.5 °C

JG-258

JG-258 is an inactive negative control for Hsp70 inhibitors[1].

  • CAS Number: 2241517-83-7
  • MF: C20H22ClN3OS3
  • MW: 452.06
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CPDA

CPDA is a novel potent SH2 domain-containing inositol phosphatase 2 (SHIP2) inhibitor that can effectively ameliorate insulin resistance in 3T3-L1 adipocytes.Target: SHIP2in vitro: CPDA was found to enhance insulin signaling.in vivo: CPDA greatly improves abnormal glucose metabolism in diabetic animals. CPDA was also found to improve the abnormal glucose metabolism in db/db mice.

  • CAS Number: 1415834-63-7
  • MF: C20H15ClF2N2O2
  • MW: 388.79500
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PR-924

A potent, specific immunoproteasome LMP7 subunit inhibitor with IC50 of 25 nM, >100-fold selectivity over β5c, β1i, β1c, β2i and β2c subunits (IC50>3 uM); shows weak activity toward LMP2 and no detectable activity toward β1, β2, or MECL1.

  • CAS Number: 1416709-79-9
  • MF: C37H38N4O5
  • MW: 618.721
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 969.0±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 539.8±34.3 °C

Anticancer agent 121

Anticancer agent 121, an inhibitor of human lactate dehydrogenase A enzyme (hLDHA), has good anticancer activities and can be used for anticancer research[1].

  • CAS Number: 2924532-47-6
  • MF: C19H18N2O3S
  • MW: 354.42
  • Catalog: Lactate Dehydrogenase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FR-229934

FR-229934 is a PDE V inhibitor extracted from patent WO2019130052A1. FR-229934 can be used for the research of pulmonary arterial hypertension and erectile dysfunction[1].

  • CAS Number: 799841-02-4
  • MF: C21H23Cl2N3O3S
  • MW: 468.39700
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Norbraylin

Norbraylin, a natural prenylated coumarin, is a PDE4D2 inhibitor with an IC50 value of 7.15 μM[1].

  • CAS Number: 60796-64-7
  • MF: C14H12O4
  • MW: 244.243
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 471.1±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 185.2±22.2 °C