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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FASN-IN-1

FASN-IN-1 is a fatty acid synthase (FASN) inhibitor extracted from patent WO2015134790A1, compound 56[1].

  • CAS Number: 1808260-84-5
  • MF: C18H25N3O3S2
  • MW: 395.54
  • Catalog: Fatty Acid Synthase (FAS)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BIA 10-2474

BIA 10-2474 is an inhibitor of fatty acid amide hydrolase (FAAH) with IC50 values of 50 to 70mg/kg in various rat brain regions.

  • CAS Number: 1233855-46-3
  • MF: C16H20N4O2
  • MW: 300.356
  • Catalog: FAAH
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 568.3±52.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 297.5±30.7 °C

ALR1/2-IN-1

ALR1/2-IN-1 (Compound 6e) is an aldehyde reductase (ALR1) and aldose reductase (ALR2) inhibitor with IC50 values of 3.26 μM and 3.06 μM against ALR1 and ALR2, respectively. ALR1/2-IN-1 shows anticancer activity[1].

  • CAS Number: 2419233-57-9
  • MF: C18H18N4O5S2
  • MW: 434.49
  • Catalog: Aldose Reductase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EMD638683

Salubrinal is a cell-permeable and selective inhibitor of eIF2α dephosphorylation.

  • CAS Number: 1181770-72-8
  • MF: C18H18F2N2O4
  • MW: 364.34300
  • Catalog: SGK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Carfilzomib

Carfilzomib is an irreversible proteasome inhibitor with an IC50 of 5 nM in ANBL-6 and RPMI 8226 cells.

  • CAS Number: 868540-17-4
  • MF: C40H57N5O7
  • MW: 719.910
  • Catalog: Autophagy
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 975.6±65.0 °C at 760 mmHg
  • Melting Point: 204-208°C
  • Flash Point: 543.8±34.3 °C

Nampt-IN-3

Nampt-IN-3 (Compound 35) simultaneously inhibit nicotinamide phosphoribosyltransferase (NAMPT) and HDAC with IC50s of 31 nM and 55 nM, respectively. Nampt-IN-3 effectively induces cell apoptosis and autophagy and ultimately leads to cell death[1].

  • CAS Number: 2121591-52-2
  • MF: C29H25N7O2
  • MW: 503.55
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC PTPN2 degrader-2

PROTAC PTPN2 degrader-2 (example 187B) is a potent PTPN2 degrader with potential for studying cancer or metabolic diseases[1].

  • CAS Number: 2912307-38-9
  • MF: C49H49ClN6O11S2
  • MW: 997.53
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(±)-Taxifolin

(±)-Taxifolin ((±)-Dihydroquercetin) is the racemate of Taxifolin. Taxifolin exhibits important anti-tyrosinase activity. Taxifolin exhibits significant inhibitory activity against collagenase with an IC50 value of 193.3 μM[1].

  • CAS Number: 24198-97-8
  • MF: C15H12O7
  • MW: 304.252
  • Catalog: Autophagy
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 687.6±55.0 °C at 760 mmHg
  • Melting Point: 239-240ºC
  • Flash Point: 264.2±25.0 °C

Licofelone-d4

Licofelone-d4 (ML-3000-d4) is the deuterium labeled Licofelone. Licofelone (ML-3000) is a dual COX/5-lipoxygenase (5-LOX) inhibitor (IC50=0.21/0.18 μM, respectively) for the treatment of osteoarthritis. Licofelone exerts anti-inflammatory and anti-proliferative effects. Licofelone induces apoptosis, and decreases the production of proinflammatory leukotrienes and prostaglandins[1][2][3].

  • CAS Number: 1189427-04-0
  • MF: C23H18D4ClNO2
  • MW: 383.90
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tyrosinase-IN-17

Tyrosinase-IN-17 (Compound 5b) is a lipophilic, skin-permeable, and non-cytotoxic Tyrosinase inhibitor (pIC50=4.99). Tyrosinase-IN-17 can be used for research on melanin-related diseases, such as melanoma, melanogenesis, etc[1].

  • CAS Number: 2427043-61-4
  • MF: C20H23NO3
  • MW: 325.40
  • Catalog: Tyrosinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aliskiren

Aliskiren(CGP 60536) is a direct renin inhibitor with IC50 of 1.5 nM.IC50 value: 1.5 nM [1]Target: reninin vitro: Aliskiren hemifumarate appears to bind to both the hydrophobic S1/S3-binding pocket and to a large, distinct subpocket that extends from the S3-binding site towards the hydrophobic core of renin. Oral bioavailability of Aliskiren hemifumarate is 2.4% in rats, 16% in marmosets and about 2.5% in humans [2].in vivo: Aliskiren hemifumarate (< 10 mg/kg, oral) inhibits plasma renin activity and lowers blood pressure in sodium-depleted marmosets[3].Once-daily oral treatment with Aliskiren hemifumarate lowers blood pressure effectively, with a safety and tolerability profile, in patients with mild-to-moderate hypertension[4].

  • CAS Number: 173334-57-1
  • MF: C30H53N3O6
  • MW: 551.758
  • Catalog: Autophagy
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 748.4±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 406.4±32.9 °C

Raphin 1

Raphin1 is an orally bioavailable, selective inhibitor of the regulatory phosphatase PPP1R15B (R15B). Raphin1 binds strongly to the R15B-PP1c holophosphatase (Kd=33 nM), and shows ~30-fold selective in binding R15B-PP1c over R15A-PP1c. Raphin1 crosses the blood-brain barrier, and reduces organismal and molecular deficits in a mouse model of a protein misfolding disease[1].

  • CAS Number: 2022961-17-5
  • MF: C8H8Cl2N4
  • MW: 231.08
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HIV protease-IN-1

HIV protease-IN-1 (compound 1·succinate) is a potent HIV protease non-peptidic inhibitor, can be used to research AIDS[1].

  • CAS Number: 2511547-82-1
  • MF: C39H40ClF7N10O7
  • MW: 929.24
  • Catalog: HIV Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BI-1230

BI-1230 is potent and orally active digit nanomolar inhibitor of HCV NS3 protease and of viral replication. BI-1230 is also highly selective against other serine/cysteine proteases. BI-1230 shows good Pharmacokinetic(PK) activity[1].

  • CAS Number: 849022-32-8
  • MF: C42H52N6O9S
  • MW: 816.96
  • Catalog: HCV Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PT2399

PT2399 is an inhibitor of HIF2α[1].

  • CAS Number: 1672662-14-4
  • MF: C17H10F5NO4S
  • MW: 419.32
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Antitumor agent-81

Antitumor agent-81 (compound 5a) is a low cytotoxic P62-RNF168 agonist that promotes the interaction of P62 with RNF168. Antitumor agent-81 induces a decrease in RNF168-mediated H2A ubiquitination and impairs homologous recombination-mediated DNA repair. Antitumor agent-81 also inhibits mice xenograft tumor growth in a dose-dependent manner[1].

  • CAS Number: 2765180-17-2
  • MF: C19H19N7O3
  • MW: 393.40
  • Catalog: E1/E2/E3 Enzyme
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TAK-981

TAK-981 is a first in class and selective inhibitor of the SUMOylation enzymatic cascade, with potential immune-activating and antineoplastic activities[1][2].

  • CAS Number: 1858276-04-6
  • MF: C25H28ClN5O5S2
  • MW: 578.10
  • Catalog: E1/E2/E3 Enzyme
  • Density: 1.474±0.06 g/cm3(Predicted)
  • Boiling Point: 836.1±75.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

Flanvotumab

Flanvotumab (IMC-20D7S) is a human monoclonal antibody targeting to tyrosinase-related protein (TYRP1), specifically expressed in melanocytes and melanoma cells. Flanvotumab acts function via natural killing-mediated antibody-dependent cell-mediated cytotoxicity (ADCC). Flanvotumab has potent anti-tumor activity and good tolerance[1].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Macbecin I

Macbecin is a stable HSP90 inhibitor by binding to the ATP-binding site with an IC50 of 2 μM and a Kd of 0.24 μM. Macbecin exhibits antitumor and cytocidal activities[1].

  • CAS Number: 73341-72-7
  • MF: C30H42N2O8
  • MW: 558.66300
  • Catalog: HSP
  • Density: 1.17g/cm3
  • Boiling Point: 736.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 399ºC

Nevanimibe hydrochloride

Nevanimibe hydrochloride (PD-132301 hydrochloride; ATR101 hydrochloride) is a selective and potent acyl-coenzyme A:cholesterol O-acyltransferase 1 (ACAT1) inhibitor with an EC50 of 9 nM. Nevanimibe hydrochloride (PD-132301 hydrochloride; ATR101 hydrochloride) inhibits ACAT2 with an EC50 of 368 nM[1].

  • CAS Number: 133825-81-7
  • MF: C27H40ClN3O
  • MW: 458.07900
  • Catalog: Acyltransferase
  • Density: N/A
  • Boiling Point: 528.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 273.2ºC

Vicenin -3

Vicenin 3 is an angiotensin-converting enzyme (ACE) inhibitor (IC50=46.91 μM) from the aerial parts of Desmodium styracifolium[1].

  • CAS Number: 59914-91-9
  • MF: C26H28O14
  • MW: 564.492
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: 935.0±65.0 °C at 760 mmHg
  • Melting Point: >250℃
  • Flash Point: 314.3±27.8 °C

W-7 hydrochloride

W-7 hydrochloride is a selective calmodulin antagonist. W-7 hydrochloride inhibits the Ca2+-calmodulin-dependent phosphodiesterase and myosin light chain kinase with IC50 values of 28 μM and 51 µM, respectively[1][2]. W-7 hydrochloride induces apoptosis and has antitumor activity[3].

  • CAS Number: 61714-27-0
  • MF: C16H22Cl2N2O2S
  • MW: 377.329
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: 518.8ºC at 760 mmHg
  • Melting Point: 220-222 °C
  • Flash Point: 267.6ºC

PAT-347

PAT-347 is an Autotaxin (ATX) inhibitor. ATX is a secretory enzyme that hydrolyzes lysophosphatidylcholine (LPC) and regulates lysophosphatidic acid (LPA) production in the blood[1][2].

  • CAS Number: 1689554-51-5
  • MF: C28H21ClF2N2O3S
  • MW: 538.99
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC6/HSP90-IN-1

HDAC6/HSP90-IN-1 (compound 17) is a potent and selective dual inhibitor of HDAC6 and HSP90, with IC50 values of 4.3 and 46.8 nM, respectively. HDAC6/HSP90-IN-1 down-regulates PD-L1 expression in INF-γ treated H1975 lung cancer cells. HDAC6/HSP90-IN-1 inhibits tumor growth in human H1975 xenograft mice[1].

  • CAS Number: 2411955-43-4
  • MF: C28H37N3O6
  • MW: 511.61
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Anticancer agent 144

Anticancer agent 144 (compound 444) is a dual PTPN2/PTP1B inhibitor with IC50 values <2.5 nM. Anticancer agent 144 can be used in cancer research[1].

  • CAS Number: 2948340-59-6
  • MF: C19H15BrF2N3O6PS2
  • MW: 594.34
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cathepsin L inhibitor

Z-FY-CHO (Z-Phe-Tyr-CHO) is a potent and specific cathepsin L (CTSL) inhibitor[1][2].

  • CAS Number: 167498-29-5
  • MF: C26H26N2O5
  • MW: 446.49500
  • Catalog: Cathepsin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SGK1-IN-2

SGK1-IN-2 (14h) is a selective SGK1 (serum and glucocorticoid regulated kinase 1) inhibitor, with an IC50 of 5 nM at 10 μM ATP concentration[1].

  • CAS Number: 1426214-64-3
  • MF: C17H12Cl2N6O2S
  • MW: 435.29
  • Catalog: SGK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ZLN005

ZLN005 is a novel transcriptional regulator of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α).IC50 value:Target: PGC-1αin vitro: ZLN005 increases expression of the PGC-1α gene in L6 myotubes. ZLN005 increased PGC-1α mRNA levels in a dose-dependent manner; 20 μmol/L ZLN005 caused a threefold increase over the control after 24 h. At 10 μmol/L, the PGC-1α mRNA levels were increased to almost the same extent at 16 to 48 h [1]. ZLN005 did not increase the expression of the PGC-1α gene in rat primary hepatocytes. AMP-activated protein kinase is involved in the mechanism inducing PGC-1α in L6 myotubes [1]in vivo: An insulin tolerance test revealed that treatment with ZLN005 significantly decreased insulin resistance in db/db mice, as evidenced by the approximately 18% decrease in the AUC. A PTT also was performed in db/db mice, and ZLN005 improved pyruvate tolerance, as evidenced by the 16% decrease in the AUC. In db/db mice, plasma NEFA and triglyceride levels were decreased by 20% and 37%, respectively, and cholesterol was decreased by 10% with ZLN005 treatment. Plasma insulin and β-hydroxybutyrate content, liver/bodyweight index and adipose composition, and muscle and liver triglyceride levels, however, were not ameliorated by treatment with ZLN005 or metformin [1].

  • CAS Number: 49671-76-3
  • MF: C17H18N2
  • MW: 250.338
  • Catalog: PGC-1α
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 415.3±38.0 °C at 760 mmHg
  • Melting Point: 257-258℃
  • Flash Point: 205.4±13.2 °C

Tyrosinase-IN-11

Tyrosinase-IN-11 is a potent tyrosinase inhibitor with IC50s of 50 nM and 64 nM for L-tyrosinase and L-dopa, respectively. Tyrosinase-IN-11 has significant antioxidant activity and low cytotoxicity. Tyrosinase-IN-11 has the potential for skin hyperpigmentation research[1].

  • CAS Number: 240797-64-2
  • MF: C15H14O5
  • MW: 274.27
  • Catalog: Tyrosinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ACT-678689

ACT-678689 (Compound Example 1.53.4) is a tryptophan hydroxylase (TPH) inhibitor with an IC50 of 8 nM[1].

  • CAS Number: 1783256-96-1
  • MF: C23H22ClFN6O4S2
  • MW: 565.040
  • Catalog: Tryptophan Hydroxylase
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A