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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FK-448 Free base

FK-448 Free base is an effective and specific inhibitor of chymotrypsin, with an IC50 of 720 nM.

  • CAS Number: 85858-76-0
  • MF: C25H30N2O3
  • MW: 406.52
  • Catalog: Proteasome
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

K134

K134 is a phosphodiesterase 3 (PDE3) inhibitor. The IC50s of K134 toward PDE3A, PDE3B, PDE5, PDE2 and PDE4 are 0.1, 0.28, 12.1, >300 and >300 µM, respectively.

  • CAS Number: 189362-06-9
  • MF: C22H29N3O4
  • MW: 399.48300
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PD125754

PD125754 is an oligopeptide renin inhibitor (IC50: 22 nM)[1].

  • CAS Number: 124339-32-8
  • MF: C42H65N5O7
  • MW: 751.99500
  • Catalog: Renin
  • Density: 1.14g/cm3
  • Boiling Point: 993.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 554.5ºC

danshenol A

Danshenol A, an abietane-type diterpenoid, is an aldose reductase (AR) inhibitor with an IC50 of 0.1 μM. Danshenol A can protect endothelial cells from oxidative stress by directly scavenging ROS. Danshenol A has anti-inflammatory and antitumor properties. Danshenol A can be used for atherosclerosis research[1][2][3][4].

  • CAS Number: 189308-08-5
  • MF: C21H20O4
  • MW: 336.38100
  • Catalog: Aldose Reductase
  • Density: 1.31±0.1 g/cm3
  • Boiling Point: 571.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 206.6ºC

Sitagliptin fenilalanil

Sitagliptin fenilalanil is a dipeptidyl aminopeptidase 4 (DPP-4) inhibitor[1].

  • CAS Number: 1339955-03-1
  • MF: C25H24F6N6O2
  • MW: 554.49
  • Catalog: Dipeptidyl Peptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mca-PLGL-Dpa-AR-NH2

Mca-PLGL-Dpa-AR-NH2 is a fluorescent peptide MMP substrate[1].

  • CAS Number: 1135689-33-6
  • MF: C43H66N12O11
  • MW: 927.06
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nortadalafil

Nortadalafil is demethyl Tadalafil, which is a PDE5 inhibitor, currently marketed in pill form for treating erectile dysfunction (ED) under the name Cialis; and under the name Adcirca for the treatment of pulmonary arterial hypertension.IC50 value:Target:

  • CAS Number: 171596-36-4
  • MF: C21H17N3O4
  • MW: 375.377
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 718.6±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 388.4±32.9 °C

Phenidone

Phenidone, an orally active dual inhibitor of cyclooxygenase (COX) and lipoxygenase (LOX), ameliorates rat paralysis in experimental autoimmune encephalomyelitis. Phenidone is a potent hypotensive agent in the spontaneously hypertensive rat[1][2]. Phenidone is used as a photographic developer[3].

  • CAS Number: 92-43-3
  • MF: C9H10N2O
  • MW: 162.189
  • Catalog: COX
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 304.1±25.0 °C at 760 mmHg
  • Melting Point: 119-121 °C(lit.)
  • Flash Point: 137.7±23.2 °C

KLK7/ELA2-IN-1

KLK7/ELA2-IN-1 is a potent kallikrein-related peptidase 7 (KLK7) and epidermal elastase 2 (ELA2) inhibitor with IC50s of 6 nM and 55 nM, respectively (WO2009024527A1, Example 4)[1].

  • CAS Number: 1122484-55-2
  • MF: C46H72N8O12
  • MW: 929.11
  • Catalog: Elastase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CYP3A4-IN-1

CYP3A4-IN-1 (compound 5a) is a potent cytochrome P450 3A4 (CYP3A4) inhibitor with an IC50 value of 0.085 µM[1].

  • CAS Number: 2771297-34-6
  • MF: C31H37N5O3S
  • MW: 559.72
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VBY-825

VBY-825 is a novel, reversible cathepsin inhibitor with high potency against cathepsins B, L, S and V.IC50 value: Target: 130/250/250/330/2.3/4.7 nM(Ki for cathepsin S/L/ZV/Bhumanized-rabbit cathepsin K/cathepsin F) [1]VBY-825 is a potent inhibitor of the assayed cathepsins and its potency against at least one cathepsin, cathepsin S, extends across species relevant for pharmacology studies, specifically mouse. 10 mg/kg/day dose of VBY-825 achieves a trough plasma concentration >200nM, which is well above that required for full inhibition of the intracellular activity of cathepsins B, F, K, L, S and V in both mouse and human cell lines.

  • CAS Number: 1310340-58-9
  • MF: C23H29F4N3O5S
  • MW: 535.55200
  • Catalog: Cathepsin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SHP836

SHP836 is a distinct, allosteric site 2 SHP2 inhibitor with IC50 of 12 uM (SHP2 1-525), and selective over the phosphatase domain (SHP2 PTP IC50>100 uM).downregulates DUSP6 mRNA, a downstream MAPK pathway marker, in KYSE-520 cancer cells; enhances pharmacological pathway inhibition in cells combined with SHP099.

  • CAS Number: 1957276-35-5
  • MF: C16H19Cl2N5
  • MW: 352.263
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EMODICACID

Emodic acid (NSC624610) is an anthraquinone compound isolated from A. microcarpus, which can inhibit the proliferation of cancer cells by inhibiting the activity of NF-κB. Emodic acid can also inhibit the phosphorylation of p38, ERK and JNK, the secretion of tumor-promoting cytokines IL-1β and IL-6, and the expression of VEGF and MMP, thereby inhibiting the invasion and migration potential of cancer cells[1].

  • CAS Number: 478-45-5
  • MF: C15H8O7
  • MW: 300.22000
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GYKI 47261 dihydrochloride

GYKI-47261 dihydrochloride is a competitive, orally active, and selective AMPA receptor antagonist with an IC50 of 2.5 μM. GYKI-47261 has broad spectrum anticonvulsive activity and neuroprotective effects. GYKI-47261 dihydrochloride is also a potent inducer of CYP2E1[1][2].

  • CAS Number: 1217049-32-5
  • MF: C18H17Cl3N4
  • MW: 395.713
  • Catalog: iGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Calcineurin autoinhibitory peptide

Calcineurin autoinhibitory peptide is a selective inhibitor of Ca2+/calmodulin-dependent protein phosphatase (calcineurin), with an IC50 of ~10 μM. Calcineurin autoinhibitory peptide could protect neurons from excitatory neuronal death[1][2].

  • CAS Number: 148067-21-4
  • MF: C124H205N39O39S2
  • MW: 2930.32000
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mephenytoin-d3

(Rac)-Mephenytoin-d3 is a labelled racemic Mephenytoin. Mephenytoin, an anticonvulsant, is the CYP2C19 and CYP2B6 substrate[1].

  • CAS Number: 1185101-86-3
  • MF: C12H11D3N2O2
  • MW: 221.27000
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VT-464 (racemate)

Seviteronel (VT-464) racemate is the racemate form of Seviteronel (VT-464), which is a potent CYP17 lyase inhibitor(h-Lyase IC50=nM)inhibition.

  • CAS Number: 1375603-36-3
  • MF: C18H17F4N3O3
  • MW: 399.33900
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RP-64477

RP-64477 is a potent inhibitor of the cholesterol esterifying enzyme Acyl-coenzyme A:cholesterol O-acyltransferase (ACAT).

  • CAS Number: 135239-65-5
  • MF: C29H42N2O3S
  • MW: 498.720
  • Catalog: Acyltransferase
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 580.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 304.8±30.1 °C

Cilazapril Monohydrate

Cilazapril Monohydrate is a angiotensin-converting enzyme (ACE) inhibitor used for the treatment of hypertension and congestive heart failure.Target: ACECilazapril is a new nonthiol group containing angiotensin converting enzyme (ACE) inhibitor. Cilazapril has been investigated in more than 4000 patients with all degrees of hypertension, as well as in the special patient groups such as the elderly, renally impaired, and patients with concomitant diseases, such as congestive cardiac failure or chronic obstructive pulmonary disease [1]. Cilazapril is a very potent and highly effective converting enzyme inhibitor. Doses well below 5 mg/day will probably suffice for therapeutic efficacy [2].

  • CAS Number: 92077-78-6
  • MF: C22H33N3O6
  • MW: 435.51400
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: N/A
  • Boiling Point: 598.1ºC at 760mmHg
  • Melting Point: 98° (dec)
  • Flash Point: 315.5ºC

Hexadecanoate-13C16 potassium

Hexadecanoate-13C16 potassium is the 13C-labeled Hexadecanoate sodium. Hexadecanoate-13C16 potassium 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: 1458714-74-3
  • MF: 13C16H31KO2
  • MW: 310.40
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Teglarinad chloride

Teglarinad chloride (GMX1777) is a prodrug of GMX1778 (a nicotinamide phosphoribosyl transferase inhibitor). Teglarinad chloride exhibits antitumor activity in mice can be attributed to inhibition of NAMPT. Teglarinad chloride also enhances radiation efficacy, mediated by interference with DNA repair and antiangiogenesis[1][2].

  • CAS Number: 432037-57-5
  • MF: C30H43Cl2N5O8
  • MW: 672.59700
  • Catalog: Nampt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 158-159ºC
  • Flash Point: N/A

Dihydroxythiobinupharidine

6,6′-Dihydroxythiobinupharidine is a cysteine proteases inhibitor. 6,6′-Dihydroxythiobinupharidine can enhance DNA cleavage mediated by human topoisomerase IIα and IIβ ~8-fold and ~3-fold, respectively[1][2].

  • CAS Number: 30343-70-5
  • MF: C30H42N2O4S
  • MW: 526.73
  • Catalog: Cathepsin
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 667.3±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 357.4±31.5 °C

2'-Ethyl Simvastatin

2'-Ethyl Simvastatin (compound 6) is a Mevinolin analog, with HMG-CoA reductase inhibition[1].

  • CAS Number: 79902-42-4
  • MF: C23H34O5
  • MW: 390.51300
  • Catalog: HMG-CoA Reductase (HMGCR)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ASB 14780

ASB 14780 (ASB14780, ASB-14780) is a potent, selective and orally active cytosolic phospholipase A2α (cPLA2α) inhibitor with IC50 of 20 nM; displays excellen selectivity over other known secreted phospholipase A2s (sPLA2s), such as sPLA2-IA, sPLA2-IIA, sPLA2-III, and sPLA2-IB; markedly ameliorates liver injury and hepatic fibrosis, attenuates the CCl4-induced expression of α-SMA protein and the mRNA expression of collagen 1a2, α-SMA, and TGF-β1 in the liver, and inhibits the expression of monocyte/macrophage markers, CD11b and MCP-1 in vivo, while preventing the recruitment of monocytes/macrophages to the liver.

  • CAS Number: 1069046-00-9
  • MF: C31H27NO3·C4H11NO3
  • MW: 582.686
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ROR gamma-t-IN-1

GSK805 is a potent, orally bioavailable RORγγ Inhibitor with pIC50 of 8.4 and >8.2 for RORγ FRET assay and Th17 assay.

  • CAS Number: 1426802-50-7
  • MF: C23H18Cl2F3NO4S
  • MW: 532.359
  • Catalog: ROR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 617.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 327.0±31.5 °C

RORγt Inverse agonist 2

RORγt Inverse agonist 2 is a selective, orally active RORγt inverse agonist with an EC50 of 119 nM[1].

  • CAS Number: 1801197-92-1
  • MF: C27H25F8NO5S
  • MW: 627.54
  • Catalog: ROR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SRI 62320

(3R,5S)-Fluvastatin ((3R,5S)-XU 62-320) sodium is the 3R,5S-isomer Fluvastatin. Fluvastatin (XU 62-320 free acid) is a first fully synthetic, competitive HMG-CoA reductase inhibitor with an IC50 of 8 nM. Fluvastatin protects vascular smooth muscle cells against oxidative stress through the Nrf2-dependent antioxidant pathway[1][2][3].

  • CAS Number: 94061-80-0
  • MF: C24H25FNNaO4
  • MW: 433.45
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PTPN22-IN-1

PTPN22-IN-1 is a potent PTPN22 inhibitor (IC50=1.4 µM; Ki=0.50 µM). PTPN22-IN-1 exhibits >7-10 fold selectivity for PTPN22 over similar phosphatases. PTPN22-IN-1 augments antitumor immune responses[1]. From WO2021007491A1 compound L-1.

  • CAS Number: 2580935-57-3
  • MF: C26H21N3O5
  • MW: 455.46
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BRL-50481

BRL-50481 is a novel and selective inhibitor of PDE7 with IC50s of 0.15, 12.1, 62 and 490 μM for PDE7A, PDE7B, PDE4 and PDE3, respectively.

  • CAS Number: 433695-36-4
  • MF: C9H12N2O4S
  • MW: 244.26800
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.334g/cm3
  • Boiling Point: 391.1ºC at 760 mmHg
  • Melting Point: 73 °C
  • Flash Point: 190.4ºC

4-Biphenylac-Cys(Me)-D-Arg-Phe-(2-phenylethyl)amide

Cathepsin L-IN-3 is a tripeptide-sized cathepsin L inhibitor.

  • CAS Number: 478164-48-6
  • MF: C41H49N7O4S
  • MW: 735.93700
  • Catalog: Cathepsin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A