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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HaloPROTAC-E

HaloPROTAC-E is a novel HaloPROTAC potent degrader, inducing reversible degradation of two endosomally localized proteins, SGK3 and VPS34, with a DC50 of 3-10 nM, remarkably selective inducing only degradation of the Halo tagged endogenous VPS34 complex (VPS34, VPS15, Beclin1, and ATG14).

  • CAS Number: 2365478-58-4
  • MF: C39H56ClN5O8S
  • MW: 790.41
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LONAFARNIB

(Rac)-Lonafarnib (Sch66336 racemate) is the racemate of Lonafarnib. Lonafarnib is a potent and orally active farnesyl transferase (FTase) inhibitor. Lonafarnib inhibits the activities of H-ras, K-ras and N-ras with IC50 values of 1.9 nM, 5.2 nM and 2.8 nM, respectively. Lonafarnib also has anti-hepatitis delta virus (HDV) activities[1].

  • CAS Number: 193275-86-4
  • MF: C27H31Br2ClN4O2
  • MW: 638.822
  • Catalog: Farnesyl Transferase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 710.4±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 383.5±35.7 °C

NDI-091143

NDI-091143 is a novel ATP-citrate lyase inhibitor.

  • CAS Number: 2375840-87-0
  • MF: C20H14ClF2NO5S
  • MW: 453.84
  • Catalog: ATP Citrate Lyase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Desirudin

Desirudin (CGP 39393) is a thrombin inhibitor. Desirudin can inhibit the formation of blood clots and venous stasis thrombosis, which is used for the research of thrombocytopenia or platelet dysfunction[1][2].

  • CAS Number: 120993-53-5
  • MF: C287H440N80O110S6
  • MW:
  • Catalog: Thrombin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ciluprevir

Ciluprevir(BILN 2061) is a specific and potent peptidomimetic inhibitor of the HCV NS3 protease with an IC50 of 3.0 nM.

  • CAS Number: 300832-84-2
  • MF: C40H50N6O8S
  • MW: 774.93
  • Catalog: HCV
  • Density: 1.4±0.0 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N[2-(4-Oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)ethyl]quinoline-3-carboxamide Hydrochloride

BML-280 (VU0285655-1) is a potent and selective phospholipase D2 (PLD2) inhibitor. BML-280 has the ability to prevent caspase-3 cleavage and reduction in cell viability induced by high glucose. BML-280 can be used for rheumatoid arthritis research[1][2].

  • CAS Number: 1158347-73-9
  • MF: C25H27N5O2
  • MW: 429.51400
  • Catalog: Interleukin Related
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Kushenol B

Kushenol B is an isoprenoid flavonoid isolated from S. flavescens, has antimicrobial, anti-inflammatory and antioxidant activities[1]. Kushenol B has inhibitory activity against cAMP phosphodiesterase (PDE), with an IC50 of 31 µM[1].

  • CAS Number: 99217-64-8
  • MF: C30H36O6
  • MW: 492.603
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 702.3±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 228.2±26.4 °C

ER-000444793

ER-000444793 is a potent inhibitor of mitochondrial permeability transition pore (mPTP) opening. ER-000444793 inhibits mPTP with an IC50 of 2.8 μM.

  • CAS Number: 792957-74-5
  • MF: C23H18N2O2
  • MW: 354.4
  • Catalog: Mitochondrial Metabolism
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ganoderic Acid C6

Ganoderic acid C6 has aldose reductase inhibitory activity[1].

  • CAS Number: 105742-76-5
  • MF: C30H42O8
  • MW: 530.65
  • Catalog: Aldose Reductase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 708.3±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 396.1±29.4 °C

Gemlapodect

Gemlapodect (RO554965) is an inhibitor of phosphodiesterase 10A (PDE10A). Gemlapodect can be used for researching schizophrenia[1].

  • CAS Number: 1380329-87-2
  • MF: C22H21N7O3
  • MW: 431.45
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK-356278

GSK356278 is a potent, selective, orally bioavailable and brain-penetrant inhibitor of phosphodiesterase 4 (PDE4), with pIC50s of 8.6, 8.8, and 8.7 for human PDE4A, PDE4B, and PDE4D, respectively. GSK356278 has anti-inflammatory activity, and exhibits anxiolytic and cognition-enhancing effects[1].

  • CAS Number: 720704-34-7
  • MF: C21H25N7O2S
  • MW: 439.53400
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SM 7368

SM-7368 is a potent NF-kB inhibitor that targets downstream of MAPK p38 activation[1]. SM-7368 inhibits TNF-α-induced MMP-9 upregulation. SM-7368 can be used for the research of chemotherapies targeting TNF-α-mediated tumor invasion and metastasis [2].

  • CAS Number: 380623-76-7
  • MF: C10H5ClN4O5S
  • MW: 328.68900
  • Catalog: p38 MAPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SF1670

SF1670 is a potent and specific phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibitor.

  • CAS Number: 345630-40-2
  • MF: C19H17NO3
  • MW: 307.343
  • Catalog: Phosphatase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 554.1±29.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 208.0±24.4 °C

IDH1 Inhibitor 2

IDH1 Inhibitor 2 is a potent IDH1 inhibitor via a direct covalent modification of His315, with an IC50 of 110 nM[1].

  • CAS Number: 2244895-42-7
  • MF: C26H22N4O
  • MW: 406.48
  • Catalog: Isocitrate Dehydrogenase (IDH)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SEW84

SEW84 (SEW04784) is a first-in-class, specific inhibitor of the Aha1-stimulated Hsp90 (ASH) ATPase activity (IC50=0.3 uM) without inhibiting basal Hsp90 ATPase;SEW84 binds to the C-terminal domain of Aha1 (Kd=1.7 uM) to weaken its asymmetric binding to Hsp90.SEW84 inhibited the GR- and AR-dependent luciferase expression with IC50 of 1.3 uM and 0.7 uM respectively.SEW84 blocks Aha1-dependent Hsp90 chaperoning activities, including the in vitro and in vivo refolding of firefly luciferase, and the transcriptional activity of the androgen receptor in cell-based models of prostate cancer.SEW84 promotes the clearance of phosphorylated tau in cellular and tissue models of neurodegenerative tauopathy.

  • CAS Number: 259089-67-3
  • MF: C19H14F4N4Os
  • MW: 422.402
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-Phenyl-1,2,5-thiadiazolidin-3-one 1,1-dioxide

PTP1B-IN-1 is a potent protein tyrosine phosphatase-1B (PTP1B) inhibitor with IC50 of 1.6 mM; 1,2,5-thiadiazolidin-3-one-1,1-dioxide scaffold for derivatives synthesis.

  • CAS Number: 612530-44-6
  • MF: C8H8N2O3S
  • MW: 212.22600
  • Catalog: Phosphatase
  • Density: 1.483
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Andrastin A

Andrastin A meroterpenoid compound, is a farnesyltransferase inhibitor. Andrastin A inhibits the efflux of anticancer compounds from multidrug-resistant cancer cells. Andrastin A can be isolated from Penicillium species[1][2].

  • CAS Number: 174232-42-9
  • MF: C28H38O7
  • MW: 486.59700
  • Catalog: Farnesyl Transferase
  • Density: 1.19g/cm3
  • Boiling Point: 560.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 236.1ºC

TAS4464

TAS4464 is a highly potent and selective inhibitor of NEDD8 activating enzyme (NAE), with an IC50 of 0.955 nM[1].

  • CAS Number: 1848959-10-3
  • MF: C21H23FN6O6S
  • MW: 506.51
  • Catalog: NEDD8-activating Enzyme
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CP671305

CP671305 is a potent, orally active, selective inhibitor of phosphodiesterase-4-D, and possesses high activities.

  • CAS Number: 445295-04-5
  • MF: C23H19FN2O7
  • MW: 454.405
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 664.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 355.4±31.5 °C

Vardenafil-d5

Vardenafil-d5 is deuterium labeled Vardenafil. Vardenafil is a selective, orally active, potent inhibitor of phosphodiesterase-5 (PDE5), with an IC50 of 0.7 nM. Vardenafil shows selectivity over PDE1 (180 nM), PDE6 (11 nM), PDE2, PDE3, and PDE4 (>1000 nM). Vardenafil competitively inhibits cyclic guanosine monophosphate (cGMP) hydrolysis and thus increases cGMP levels. Vardenafil can be used for the research of erectile dysfunction[1][2].

  • CAS Number: 1189685-70-8
  • MF: C23H27D5N6O4S
  • MW: 493.63
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 692.3±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 372.5±34.3 °C

Kongensin A

Kongensin A is a natural product isolated from Croton kongensis. Kongensin A is an effective, covalent HSP90 inhibitor that blocks RIP3-dependent necroptosishas. Kongensin A is a potent necroptosis inhibitor and an apoptosis inducer. Kongensin A has potential anti-necroptosis and anti-inflammation applications[1].

  • CAS Number: 885315-96-8
  • MF: C22H30O5
  • MW: 374.471
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 525.7±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 178.4±23.6 °C

Linagliptin-13C,d3

Linagliptin-13C,d3 is the 13C- and deuterium labeled. Linagliptin is a highly potent, selective DPP-4 inhibitor with IC50 of 1 nM.

  • CAS Number: 1398044-43-3
  • MF: C2413CH25D3N8O2
  • MW: 476.55
  • Catalog: Ferroptosis
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LE 135

LE135 is a potent RAR antagonist that binds selectively to RARα (Ki of 1.4 μM) and RARβ (Ki of 220 nM), and has a higher affinity to RARβ. LE135 is highly selective over RARγ, RXRα, RXRβ and RXRγ. LE135 is also a potent TRPV1 and TRPA1 receptors activator with EC50s of 2.5 μM and 20 μM, respectively[1][2].

  • CAS Number: 155877-83-1
  • MF: C29H30N2O2
  • MW: 438.561
  • Catalog: TRP Channel
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 601.3±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 317.5±31.5 °C

COX-2/5-LOX-IN-3

COX-2/5-LOX-IN-3 (compound 5b) is a potent and dual COX-2/5-LOX inhibitor with IC50 values of 45.73, 5.45 and 4.33 μM for COX-1, COX-2, and 5-LOX, respectively. COX-2/5-LOX-IN-3 has the potential for the research of inflammation diseases[1].

  • CAS Number: 2481484-51-7
  • MF: C17H16ClN3O2S
  • MW: 361.85
  • Catalog: COX
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VU0359595

VU0359595 (CID-53361951; ML-270) is a potent and selective pharmacological phospholipase D1 (PLD1) inhibitor with an IC50 of 3.7 nM. VU0359595 is >1700-fold selective for PLD1 over PLD2 (IC50 of 6.4 μM). VU0359595 can be used for the research of cancer, diabetes, neurodegenerative and inflammatory diseases[1][2][3][4].

  • CAS Number: 1246303-14-9
  • MF: C25H29BrN4O2
  • MW: 497.427
  • Catalog: Phospholipase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UAMC 00039 dihydrochloride

UAMC00039 dihydrochloride is a potent, reversible and competitive dipeptidyl peptidase II inhibitor with an IC50 of 0.48 nM.

  • CAS Number: 697797-51-6
  • MF: C16H26Cl3N3O
  • MW: 382.756
  • Catalog: Dipeptidyl Peptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 trifluoroacetate salt

Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 (FS-6) is a fluorescent peptide that is a quenched MMP peptide substrate. Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 can be used for real-time quantification of MMP enzymatic activity. Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 is an elongated peptide of MMP substrate (FS-1) and is active against collagenases (MMP-1, MMP-8, MMP-13 ) and MT1-MMP with higher specificity constants than FS-1[1]. (Ex/Em=325 nm/400 nm)

  • CAS Number: 720710-69-0
  • MF: C55H80N16O16
  • MW: 1221.32
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

voxilaprevir

Voxilaprevir (GS-9857) is a fluorinated macrocyclic hepatitis C virus (HCV) nonstructural protein (NS) 3/4A protease inhibitor with potent in vitro antiviral activity against genotypes 1-6 HCV and broad coverage of NS3/4A protease polymorphisms. GS-9857 improves coverage against commonly encountered NS3 resistance-associated variants (RAVs)[1][2].

  • CAS Number: 1535212-07-7
  • MF: C40H52F4N6O9S
  • MW: 868.93400
  • Catalog: HCV Protease
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Z-Val-Gly-Arg-pNA

Z-Val-Gly-Arg-pNA is a chromogenic substrate for urokinase. Z-Val-Gly-Arg-pNA can be used for determination of urokinase activity[1].

  • CAS Number: 78333-16-1
  • MF: C27H36N8O7
  • MW: 584.624
  • Catalog: Ser/Thr Protease
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MMP-9-IN-6

MMP-9-IN-6 (Compound 3g) is a MMP-9 inhibitor with IC50 value of 50 μM, which has good anti-ulcer effect[1].

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