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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FTI-2148

FTI-2148 is a RAS C-terminal mimetic dual farnesyl transferase (FT-1) and geranylgeranyl transferase-1 (GGT-1) inhibitor with IC50s of 1.4 nM and 1.7 μM for FT-1 and GGT-1, respectively[1].

  • CAS Number: 251577-09-0
  • MF: C24H28N4O3S
  • MW: 452.569
  • Catalog: Farnesyl Transferase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 730.1±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 395.4±32.9 °C

Mutant IDH1-IN-6

Mutant IDH1-IN-6 is a potent, selective and orally active mutant isocitrate dehydrogenase (IDH) inhibitor with IC50s of 6.27 nM, 3.71 nM, 36.9 nM and 11.5 nM for IDH1 R132H, IDH1 R132C, IDH2 R140Q and IDH2 R172K mutant enzymes, respectively. Mutant IDH1-IN-6 is less active at inhibiting the IDH wild-type enzymes[1].

  • CAS Number: 2230263-60-0
  • MF: C28H36N6O3
  • MW: 504.62
  • Catalog: Isocitrate Dehydrogenase (IDH)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Flovagatran

Flovagatran (TGN 255) is a potent and reversible thrombin inhibitor (Ki: 9 nM). Flovagatran can be used in the research of arterial and venous thrombosis[1].

  • CAS Number: 871576-03-3
  • MF: C27H36BN3O7
  • MW: 525.40200
  • Catalog: Thrombin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cabotegravir-d5

Cabotegravir-d5 is deuterium labeled Cabotegravir.

  • CAS Number: 2750534-77-9
  • MF: C19H12D5F2N3O5
  • MW: 410.38
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EHNA.HCl

EHNA hydrochloride is a specific inhibitor of adenosine deaminase, prevents dAdo degradation and increases mitochondrial dATP levels in fibroblasts[1].

  • CAS Number: 58337-38-5
  • MF: C14H24ClN5O
  • MW: 313.826
  • Catalog: Adenosine Deaminase
  • Density: 1.27g/cm3
  • Boiling Point: 478.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 243ºC

2-TEDC

2-TEDC is a potent inhibitor of 5-, 12-, and 15-lipoxygenase with IC50 values of 0.09 μM, 0.013 μM and 0.5 μM, respectively. 2-TEDC can be used for the research of atheroscrelosi[1].

  • CAS Number: 132465-10-2
  • MF: C16H13NO4S
  • MW: 315.34400
  • Catalog: 5-Lipoxygenase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

α-Lipoic Acid

α-Lipoic Acid is an antioxidant, which is an essential cofactor of mitochondrial enzyme complexes. α-Lipoic Acid inhibits NF-κB-dependent HIV-1 LTR activation.

  • CAS Number: 1077-28-7
  • MF: C8H14O2S2
  • MW: 206.326
  • Catalog: HIV
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 362.5±11.0 °C at 760 mmHg
  • Melting Point: 60-62ºC
  • Flash Point: 173.0±19.3 °C

KT182

KT182 is a potent and selective inhibitor of α/β-hydrolase domain containing 6 (ABHD6), with an IC50 of 0.24 nM in Neuro2A cells[1].

  • CAS Number: 1402612-62-7
  • MF: C27H26N4O2
  • MW: 438.52
  • Catalog: MAGL
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Eplerenone

Eplerenone is an aldosterone antagonist with an IC50 of 0.36 μM.Target: Mineralocorticoid ReceptorEplerenone is a selective mineralocorticoid receptor antagonist, which has been shown to produce sustained increases in plasma renin and serum aldosterone, consistent with inhibition of the negative regulatory feedback of aldosterone on renin secretion. The resulting increased plasma renin activity and aldosterone circulating levels do not overcome the effects of eplerenone. Eplerenone selectively binds to recombinant human mineralocorticoid receptors relative to its binding to recombinant human glucocorticoid, progesterone and androgen receptors [1]. Benefits of eplerenone therapy over placebo were also observed in several secondary outcomes, including: death from any cause or hospitalization for HF; death from any cause; hospitalization for any reason; or hospitalization for HF [2].

  • CAS Number: 107724-20-9
  • MF: C24H30O6
  • MW: 414.491
  • Catalog: Mineralocorticoid Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 597.9±50.0 °C at 760 mmHg
  • Melting Point: 241-243ºC
  • Flash Point: 259.5±30.2 °C

TAPI-0

TAPI-0 is a TACE (TNF-α converting enzyme; ADAM17) inhibitor with an IC50 of 100 nM. TAPI-0 is a MMP inhibitor and also attenuates TNF-α processing[1][2].

  • CAS Number: 163958-73-4
  • MF: C24H32N4O5
  • MW: 456.53
  • Catalog: Bacterial
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(1β,3β)-Spirosta-5,25(27)-dien-1,3-diol

Neoruscogenin, a member of the steroidal sapogenin family, is a bioavailable, potent, and high-affinity agonist of the nuclear receptor RORα (NR1F1)[1].

  • CAS Number: 17676-33-4
  • MF: C27H40O4
  • MW: 428.604
  • Catalog: ROR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 566.6±50.0 °C at 760 mmHg
  • Melting Point: 196-198℃
  • Flash Point: 296.4±30.1 °C

Carprofen

Carprofen is a nonsteroid anti-inflammatory agent, acts as a multi-target FAAH/COX inhibitor, with IC50s of 3.9 μM, 22.3 μM and 78.6 μM for COX-2, COX-1 and FAAH, respectively.

  • CAS Number: 53716-49-7
  • MF: C15H12ClNO2
  • MW: 273.714
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 509.1±35.0 °C at 760 mmHg
  • Melting Point: 186-188ºC
  • Flash Point: 261.7±25.9 °C

H-Arg-Val-Leu-psi(CH2NH)Phe-Glu-Ala-Nle-NH2

HIV-IN petide is a competitive inhibitor of HIV-1 protease (Ki=50 nM)[1].

  • CAS Number: 167875-35-6
  • MF: C40H69N11O8
  • MW: 832.04
  • Catalog: HIV
  • Density: 1.30g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CAY10434

CAY 10434 is a potent CYP4A hydroxylase inhibitor. CAY 10434 improves contractile response to angiotensin II with the maximal contractile response (Emax) 6764 mg[1].

  • CAS Number: 769917-29-5
  • MF: C17H26N3O+
  • MW: 287.400
  • Catalog: Cytochrome P450
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 435.0±30.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 216.9±24.6 °C

Coblopasvir dihydrochloride

Coblopasvir (KW-136) dihydrochloride is a pangenotypic non-structural protein 5A (NS5A) inhibitor. Coblopasvir dihydrochloride can be used for research of chronic hepatitis C virus infection[1].

  • CAS Number: 1966138-53-3
  • MF: C41H52Cl2N8O8
  • MW: 855.81
  • Catalog: HCV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-Phenyltoxoflavin

3-Phenyltoxoflavin, a derivative of Toxoflavin, is an Hsp90 inhibitor, with a Kd of 585 nM for the interaction of Hsp90-TPR2A. 3-Phenyltoxoflavin has anti-cancer activity[1][2].

  • CAS Number: 32502-63-9
  • MF: C13H11N5O2
  • MW: 269.25900
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CI-1044

CI-1044 is an orally active PDE4 inhibitor with IC50s of 0.29, 0.08, 0.56, 0.09 μM for PDE4A5, PDE4B2, PDE4C2 and PDE4D3, respectively.

  • CAS Number: 197894-84-1
  • MF: C23H19N5O2
  • MW: 397.429
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 773.2±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 421.4±32.9 °C

PF-06815345

PF-06815345 (PF 6815345) is a potent prodrug PCSK9 modulator that inhibits PCSK9 secretion in vitro translation assay; PF-06815345is identified after optimization of the prodrug moiety to maximize intestinal stability achieving liver targeting of the active compound after prodrug turnover by carboxylesterase (CES1). Hypercholesterolemia Phase 1 Discontinued

  • CAS Number: 1900686-46-5
  • MF: C27H29ClFN9O4
  • MW: 598.029
  • Catalog: Ser/Thr Protease
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 775.4±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 422.7±35.7 °C

AA38-3

AA38-3 is a serine hydrolase (SH) inhibitor. AA38-3 can inhibit three SHs, ABHD6, ABHD11, and FAAH[1].

  • CAS Number: 65815-76-1
  • MF: C12H14N2O4
  • MW: 250.25
  • Catalog: FAAH
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 397.5±34.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 194.2±25.7 °C

MLS000545091

MLS000545091 is a potent and selective lipoxygenase-2 (LOX-2) inhibitor with an IC50 value of 2.6 μM for h15-LOX-2[1].

  • CAS Number: 322666-76-2
  • MF: C14H15ClN2O
  • MW: 262.73
  • Catalog: 5-Lipoxygenase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ombitasvir

Ombitasvir is a potent inhibitor of the hepatitis C virus protein NS5A, with EC50s of 0.82 to 19.3 pM against HCV genotypes 1 to 5, and 366 pM against genotype 6a.

  • CAS Number: 1258226-87-7
  • MF: C50H67N7O8
  • MW: 894.109
  • Catalog: HCV
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 1065.6±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 598.2±34.3 °C

RS-25344 hydrochloride

RS-25344 hydrochloride is a selective cAMP-phosphodiesterase 4 (PDE 4; PDE IV) inhibitor with an IC50 of 0.28 nM in human lymphocytes. RS-25344 hydrochloride has only weak inhibitory effects on PDE I, II, III (IC50 of >100 μM, 160 μM, 330 μM, respectively). RS-25344 hydrochloride has anti-inflammatory, memory- and cognition enhancing, and antineoplastic effects[1][2].

  • CAS Number: 152815-28-6
  • MF: C19H14ClN5O4
  • MW: 411.799
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

16 alpha-Hydroxytrametenolic acid

16α-Hydroxytrametenolic acid, a natural triterpene, is a potential retinoid X receptor (RXR) selective agonist[1].

  • CAS Number: 176390-68-4
  • MF: C30H48O4
  • MW: 472.71
  • Catalog: RAR/RXR
  • Density: 1.11±0.1 g/cm3(Predicted)
  • Boiling Point: 598.3±50.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

Isotanshinone IIA

Isotanshinone IIA, an abietane-type diterpene metabolite, could non-competitively inhibit Protein Tyrosine Phosphatase 1B (PTP1B) activity with an IC50 0f 11.4 μM.

  • CAS Number: 20958-15-0
  • MF: C19H18O3
  • MW: 294.34400
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: 471.1±45.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

Cyanidin 3-sambubioside chloride

Cyanidin 3-sambubioside chloride (Cyanidin-3-O-sambubioside chloride), a major anthocyanin, a natural colorant, and is a potent NO inhibitor. Cyanidin 3-sambubioside chloride is a H274Y mutation inhibitor, and inhibits influenza neuraminidase activity with an IC50 of 72 μM. Cyanidin 3-sambubioside chloride inhibits angiotensin-converting enzyme (ACE) activity and has antioxidant, anti-angiogenic and antiviral properties[1][2][3].

  • CAS Number: 33012-73-6
  • MF: C26H29ClO15
  • MW: 616.95200
  • Catalog: Influenza Virus
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MAL3-101

MAL3-101 is a Hsc70 modulator that inhibits Hsp70 ATPase activity, exhibits antiproliferative activity in breast cancer cells SK-BR-3 with IC50 of 27 uM; also exhibits antimyeloma effects on MM cell lines in vitro and in vivo in a xenograft plasmacytoma model, as well as on primary tumor cells and bone marrow endothelial cells from myeloma patients.

  • CAS Number: 912361-26-3
  • MF: C54H66N4O10
  • MW: 931.14
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Esaxerenone

Esaxerenone is a novel, highly potent and selective non-steroidal mineralocorticoid receptor antagonist.

  • CAS Number: 1632006-28-0
  • MF: C22H21F3N2O4S
  • MW: 466.473
  • Catalog: Mineralocorticoid Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 581.3±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 305.4±30.1 °C

Anagliptin

Anagliptin is a highly selective, potent inhibitor of dipeptidyl peptidase 4 (DPP-4), with an IC50 of 3.8 nM, and less selective at DPP-8/9 (IC50, 68, 60 nM, respectively).

  • CAS Number: 739366-20-2
  • MF: C19H25N7O2
  • MW: 383.448
  • Catalog: Dipeptidyl Peptidase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ND-322 HCl

ND-322 HCl is a selective inhibitor of MT1-MMP and MMP2 and reduces in vitro melanoma cell growth, migration and invasion.

  • CAS Number: 1333379-23-9
  • MF: C15H16ClNO3S2
  • MW: 357.88
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mevastatin

Mevastatin (Compactin; ML236B) inhibits HMGCR (HMG-CoA reductase) (Ki for acid form is 1 nM) which in turn inhibits isoprenoid biosynthesis and therefore blocks protein isoprenylation and reduces plasma cholesterol levels in humans. IC50 value: 1 nM (Ki)Target: HMGCRMevastatin induces apoptosis, arrests cancer cells in G1 phase and downregulates cdk 2, 4, and 6, cyclin D1 and E1, p21 and p27. Mevastatin suppresses TNF-induced NF-κB activation (IC50 = ~17 uM), which potentiates apoptosis in human myeloid leukemia cells and thus, may be useful in treating cancer.

  • CAS Number: 73573-88-3
  • MF: C23H34O5
  • MW: 390.513
  • Catalog: Autophagy
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 555.0±50.0 °C at 760 mmHg
  • Melting Point: 151-153 °C
  • Flash Point: 186.5±23.6 °C