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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15-PGDH 5 alpha Reductase 5-Lipoxygenase Acetyl-CoA Carboxylase Acyltransferase Adenosine Deaminase Adenosine Kinase Aldehyde Dehydrogenase (ALDH) Aldose Reductase Aminopeptidase Angiotensin-converting Enzyme (ACE) ATGL ATP Citrate Lyase Carbonic Anhydrase Carboxypeptidase Cathepsin CETP COMT Cytochrome P450 Dipeptidyl Peptidase Dopamine β-hydroxylase E1/E2/E3 Enzyme Elastase Enolase FAAH FABP Factor Xa Farnesyl Transferase Fatty Acid Synthase (FAS) FXR Glucokinase GSNOR Gutathione S-transferase HCV Protease Hexokinase HIF/HIF Prolyl-Hydroxylase HIV Integrase HIV Protease HMG-CoA Reductase (HMGCR) HSP Indoleamine 2,3-Dioxygenase (IDO) Isocitrate Dehydrogenase (IDH) Lactate Dehydrogenase LXR MAGL Mineralocorticoid Receptor Mitochondrial Metabolism MMP Nampt NEDD8-activating Enzyme Neprilysin PAI-1 PDHK PGC-1α Phosphatase Phosphodiesterase (PDE) Phospholipase Procollagen C Proteinase Proteasome Pyruvate Kinase RAR/RXR Renin ROR Ser/Thr Protease SGK Stearoyl-CoA Desaturase (SCD) Thrombin Tryptophan Hydroxylase Tyrosinase Xanthine Oxidase
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TPN171

TPN171 is a potent, selective and oral bioavailable inhibitor of phosphodiesterase type 5 (PDE5) with an IC50 of 0.62 nM, being developed for the treatment of pulmonary arterial hypertension (PAH)[1].

  • CAS Number: 1229018-87-4
  • MF: C24H35N5O3
  • MW: 441.57
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Retinoic acid

Retinoic acid is a metabolite of vitamin A that plays important roles in cell growth, differentiation, and organogenesis. Retinoic acid is a natural agonist of RAR nuclear receptors, with IC50s of 14 nM for RARα/β/γ. Retinoic acid bind to PPARβ/δ with Kd of 17 nM.

  • CAS Number: 302-79-4
  • MF: C20H28O2
  • MW: 300.435
  • Catalog: Caspase
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 462.8±14.0 °C at 760 mmHg
  • Melting Point: 179-184ºC
  • Flash Point: 350.6±11.0 °C

IDO-IN-3

IDO-IN-3 is a potent indoleamine 2,3-dioxygenase (IDO) inhibitor with an IC50 of 290 nM.

  • CAS Number: 2070018-30-1
  • MF: C11H12BrFN6O2
  • MW: 359.15
  • Catalog: Indoleamine 2,3-Dioxygenase (IDO)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Oxipurinol

Oxipurinol (Oxipurinol), the major active metabolite of Allopurinol, is an inhibitor of xanthine oxidase. Oxipurinol can be used to regulate blood urate levels and treat gout[1].

  • CAS Number: 2465-59-0
  • MF: C5H4N4O2
  • MW: 152.11
  • Catalog: Xanthine Oxidase
  • Density: 2.19g/cm3
  • Boiling Point: 662.9ºC at 760 mmHg
  • Melting Point: 300 °C
  • Flash Point: 354.7ºC

Mangostanol

Mangostanol ((+)-Mangostanol)) is a natural polyoxygenated xanthone mangostanol isolated from the shell of Garcinia mangostana which has inhibitory effect on cAMP phosphodiesterase (PDE)[1].

  • CAS Number: 184587-72-2
  • MF: C24H26O7
  • MW: 426.459
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 657.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 227.0±25.0 °C

KS100

KS100 is a potent ALDH inhibitor with IC50s of 230, 1542, 193 nM for ALDH1A1, ALDH2, and ALDH3A1, respectively. KS100 shows antiproliferative and anticancer effects with low low toxic. KS100 significantly increases ROS activity, lipid peroxidation and toxic aldehyde accumulation. KS10600 induces apoptosis and cell cycle arrest at the G2/M phase[1].

  • CAS Number: 2408477-54-1
  • MF: C17H14Br3N3O2S
  • MW: 564.09
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HIV Protease Substrate IV

HIV Protease Substrate IV is a substrate of HIV protease. HIV Protease Substrate IV can be used to measure the activity of HIV (human immunodeficiency virus) -1 protease[1].

  • CAS Number: 128340-47-6
  • MF: C49H83N15O13
  • MW: 1090.28000
  • Catalog: HIV Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CC-885

CC-885 is a cereblon (CRBN) modulator with potent anti-tumour activity.

  • CAS Number: 1010100-07-8
  • MF: C22H21ClN4O4
  • MW: 440.88
  • Catalog: E1/E2/E3 Enzyme
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Febuxostat acyl glucuronide

Febuxostat acyl glucuronide (Febuxostat acyl-β-D-glucuronide) is a metabolite of Febuxostat (HY-14268). Febuxostat is a potent, selective and non-purine xanthine oxidase (XO) inhibitor[1].

  • CAS Number: 1351692-92-6
  • MF: C22H24N2O9S
  • MW: 492.50
  • Catalog: Xanthine Oxidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bergapten

Bergapten is a natural anti-inflammatory and anti-tumor agent isolated from bergamot essential oil, other citrus essential oils and grapefruit juice. Bergapten is inhibitory towards mouse and human CYP isoforms.

  • CAS Number: 484-20-8
  • MF: C12H8O4
  • MW: 216.189
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 412.4±45.0 °C at 760 mmHg
  • Melting Point: 190-193 °C(lit.)
  • Flash Point: 203.2±28.7 °C

HIF-2α-IN-9

HIF-2α-IN-9 (compound 35r) is an inhibitor ofHIF-2α. HIF-2α-IN-9 inhibits VEGF-A (IC50=305 nM), and regulates growth-promoting genes in tumor cells, reactivates macrophage-mediated tumor immunity[1].

  • CAS Number: 2648334-36-3
  • MF: C12H13F5O4S2
  • MW: 380.35
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(4R)-4-[(7-Phenylheptanoyl)amino]octanoic acid

CAY10590 (GK115) is an inhibitor of secreted phospholipase A2 (sPLA2) and can be used for the research of chronic inflammatory kidney diseases[1].

  • CAS Number: 1101136-50-8
  • MF: C21H33NO3
  • MW: 347.492
  • Catalog: Prostaglandin Receptor
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 567.8±43.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 297.2±28.2 °C

Finasteride

Finasteride is an orally active testosterone 5-alpha-reductase inhibitor (Ki= 10 nM). Target: 5-alpha ReductaseApproved: 1992Finasteride, a synthetic 4-azasteroid antiandrogen compound, is a specific inhibitor of steroid Type II 5α-reductase, an intracellular enzyme that converts the androgen testosterone into 5α-dihydrotestosterone (DHT). Finasteride is used in the treatment of prostate cancer, benign prostatic hyperplasia, and androgenetic alopecia (male pattern baldness). In benign prostatic hyperplasia, finasteride inhibits 5alpha-reductase activity in epithelium for Ki of 10 nM, significantly lower than in stroma (Ki = 33nM) [1].

  • CAS Number: 98319-26-7
  • MF: C23H36N2O2
  • MW: 372.544
  • Catalog: 5 alpha Reductase
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 576.6±50.0 °C at 760 mmHg
  • Melting Point: 253 °C
  • Flash Point: 177.4±30.3 °C

Tec Kinase-IN-21

A selective small molecule toward Tec kinase-mediated tyrosine phosphorylation of FGF2 with IC50 of 11.7 uM; inhibits Tec-FGF2 complex and blocks tyrosine phosphorylation of FGF2 in cells, also inhibit FGF2 secretion from cells.

  • CAS Number: 931664-41-4
  • MF: C16H15ClN4O2S
  • MW: 362.832
  • Catalog: Tyrosinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

S-2474

S-2474 is an inhibitor of COX-2 and 5-lipoxygenase, with IC50s of 11 nM and 27 μM for COX-2 and COX-1 in human intact cells, and used as a nonsteroidal anti-inflammatory drug.

  • CAS Number: 158089-95-3
  • MF: C20H31NO3S
  • MW: 365.53000
  • Catalog: 5-Lipoxygenase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bergamotine

Bergamottin is a potent and competitive CYP1A1 inhibitor with a Ki of 10.703 nM.

  • CAS Number: 7380-40-7
  • MF: C21H22O4
  • MW: 338.397
  • Catalog: Cytochrome P450
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 503.7±50.0 °C at 760 mmHg
  • Melting Point: 75-80ºC
  • Flash Point: 258.4±30.1 °C

PROTAC SHP2 degrader-1

PROTAC SHP2 degrader-1 is a potent and effective SHP2 degrader. PROTAC SHP2 degrader-1 induces SHP2 degradation requires binding to VHL-1 and SHP2 proteins and is also neddylation- and proteasome-dependent[1].

  • CAS Number: 2458219-65-1
  • MF: C56H79ClN12O6S2
  • MW: 1115.89
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ganetespib(STA-9090)

Ganetespib is a heat shock protein 90 (HSP90) inhibitor which exhibits potent cytotoxicity in a wide variety of hematological and solid tumor cell lines.

  • CAS Number: 888216-25-9
  • MF: C20H20N4O3
  • MW: 364.398
  • Catalog: HSP
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 685.8±57.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 368.5±32.1 °C

AFP464

AFP464, is an active HIF-1α inhibitor with an IC50 of 0.25 μM, also is a potent aryl hydrocarbon receptor (AhR) activator.

  • CAS Number: 468719-52-0
  • MF: C22H23F3N4O3
  • MW: 448.44
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Patulitrin

Patulitrin has scavenging effect in the DPPH radical. Patulitrin inhibits soybean lipoxygenase. Patulitrin also has antihypertensive effect. Patulitrin is an antioxidant flavonoid that can be isolated from Anthemis tinctoria[1][2].

  • CAS Number: 19833-25-1
  • MF: C22H22O13
  • MW: 494.40
  • Catalog: 5-Lipoxygenase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-Isobutyl-1-methylxanthine

IBMX is a broad-spectrum phosphodiesterase (PDE) inhibitor, with IC50s of 6.5, 26.3 and 31.7 μM for PDE3, PDE4 and PDE5, respectively.

  • CAS Number: 28822-58-4
  • MF: C10H14N4O2
  • MW: 222.244
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 445.6±37.0 °C at 760 mmHg
  • Melting Point: 200-201 °C(lit.)
  • Flash Point: 223.3±26.5 °C

CP 80633

Atizoram (CP-80,633), a cyclic nucleotide phosphodiesterase (PDE4) inhibitor, elevates plasma cyclic AMP levels and decreases tumor necrosis factor-α (TNFα) production in mice[1].

  • CAS Number: 135637-46-6
  • MF: C18H24N2O3
  • MW: 316.395
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 543.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 282.2±30.1 °C

Thymolphthalein monophosphate disodium hydrate

Thymolphthalein monophosphate disodium hydrate is a chromogenic substrate for the determination of acid phosphatase and alkaline phosphatase. Thymolphthalein is released during the reaction, increases the pH of the medium for easy detection, produces color and stops hydrolysis. Thymolphthalein monophosphate disodium hydrate can be used for the specific detection of prostatic phosphatase in serum[1][2].

  • CAS Number: 123359-43-3
  • MF: C28H31Na2O8P
  • MW: 572.49400
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: 683.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 367.1ºC

N-Nornuciferine

N-Nornuciferine is an aporphine alkaloid in lotus leaf that significantly inhibits CYP2D6 with IC50 and Ki of 3.76 and 2.34 μM, respectively.

  • CAS Number: 4846-19-9
  • MF: C18H19NO2
  • MW: 281.349
  • Catalog: Cytochrome P450
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 446.4±45.0 °C at 760 mmHg
  • Melting Point: 128-129 ºC
  • Flash Point: 182.8±18.2 °C

PROTAC CYP1B1 degrader-1

PROTAC CYP1B1 degrader-1 (Compound 6C), a α-naphthoflavone chimera derivative, is able to eliminate cytochrome P450 (CYP)1B1-mediated drug resistance via targeted CYP1B1 degradation, with IC50s of 95.1 and 9838.6 nM for CYP1B1 and CYP1A2, respectively. PROTAC CYP1B1 degrader-1 can be used for the research of CYP1B1-overexpressing prostate cancer[1].

  • CAS Number: 2411389-67-6
  • MF: C43H39N5O10
  • MW: 785.80
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tolcapone

Tolcapone(Ro 40-7592) is an orally active selective, potent catechol-O-methyltransferase (COMT) inhibitor. IC50 value:Target: COMTTolcapone inhibits both central and peripheral COMT. Tolcapone caused a rapid and reversible inhibition of COMT activity in erythrocytes in parallel with a dose-dependent decrease in the formation of 3-OMD. Tolcapone increased the area under the concentration-time curve and elimination half-life of levodopa. Tolcapone crosses the blood-brain barrier, and has been used for L-DOPA adjunct therapy in the treatment of Parkinson's disease.

  • CAS Number: 134308-13-7
  • MF: C14H11NO5
  • MW: 273.241
  • Catalog: COMT
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 485.6±45.0 °C at 760 mmHg
  • Melting Point: 126-128ºC
  • Flash Point: 205.7±17.2 °C

ND-336

A selective inhibitor of the gelatinases MMP2 and MMP9 and MMP13 with Ki of 85, 150 and 120 nM, respectively; has minimal effect on other MMPs; accelerates diabetic wound healing by lowering inflammation and by enhancing angiogenesis and re-epithelialization of the wound, thereby reversing the pathological condition.

  • CAS Number: 1807453-83-3
  • MF: C16H17NO3S2•HCl
  • MW: 371.902
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AC-SER-GLN-ASN-TYR-PRO-VAL-VAL-NH2

Ac-Ser-Gln-Asn-Tyr-Pro-Val-Val-NH2 is a substrato peptídico of HIV-1 protease.Ac-Ser-Gln-Asn-Tyr-Pro-Val-Val-NH2 acts as the variable substrate in a peptidolytic assay to quantify the inhibition of the protease[1][2].

  • CAS Number: 121822-32-0
  • MF: C38H58N10O12
  • MW: 846.92700
  • Catalog: HIV Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SNX-2112(PF-04928473)

SNX-2112 is an orally active Hsp90 inhibitor, with a Kd of 16 nM for Hsp90 and IC50s of 30 nM, 30 nM for Hsp90 α and Hsp90 β, also induces Her-2 degradation, and inhibits Grp94 and Trap-1, with IC50s of 10 nM, 4.275 μM and 0.862 μM, respectively.

  • CAS Number: 908112-43-6
  • MF: C23H27F3N4O3
  • MW: 464.481
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 619.8±55.0 °C at 760 mmHg
  • Melting Point: 265-266℃
  • Flash Point: 328.6±31.5 °C

MMP-2 Inhibitor I

MMP-2 Inhibitor I (OA-Hy) is a potent MMP-2 inhibitor with a Ki of 1.7 μM[1][2].

  • CAS Number: 10335-69-0
  • MF: C18H35NO2
  • MW: 297.47600
  • Catalog: MMP
  • Density: 0.921g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A