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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Tanshinone I

Tanshinone I is an inhibitor of type IIA human recombinant sPLA2 (IC50=11 μM) and rabbit recombinant cPLA2 (IC50=82 μM).

  • CAS Number: 568-73-0
  • MF: C18H12O3
  • MW: 276.286
  • Catalog: Phospholipase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 498.0±24.0 °C at 760 mmHg
  • Melting Point: 233-234ºC
  • Flash Point: 245.9±15.6 °C

IDO1-IN-18

IDO1-IN-18 (Compound 14) is a potent inhibitor of IDO1. IDO1-IN-18 has the potential for the research of cancer diseases[1].

  • CAS Number: 2328099-08-5
  • MF: C23H18F4N2O3
  • MW: 446.39
  • Catalog: Indoleamine 2,3-Dioxygenase (IDO)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK864

GSK864 is an isocitrate dehydrogenase 1 (IDH1) mutant inhibitor; inhibits IDH1 mutants R132C, R132H, and R132G with IC50 values of 8.8, 15.2 and 16.6 nM.

  • CAS Number: 1816331-66-4
  • MF: C30H31FN6O4
  • MW: 558.603
  • Catalog: Isocitrate Dehydrogenase (IDH)
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 782.9±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 427.3±32.9 °C

AM 2394

AM-2394 is a structurally distinct glucokinase activator (GKA). AM-2394 activates glucokinase (GK) with an EC50 of 60 nM.

  • CAS Number: 1442684-77-6
  • MF: C22H25N5O4
  • MW: 423.47
  • Catalog: Glucokinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ONO-5334

A potent, selective, orally active inhibitor of cathepsin K with Ki of 0.1 nM, 0.049 nM and 0.85 nM for human, rabbit and rat cathepsin K, respectively; shows less or no potentcy for human cathepsin S/L/B/C (Ki=0.83/1.7/32/2500 nM); inhibits human osteoclasts bone resorption in vitro at a concentration more than 100 fold lower than that of alendronate; reduces plasma calcium level increased by PTHrP in thyroparathyroidectomized rats, decreases serum and urine C-telopeptide of type I collagen level. Osteoporosis Phase 2 Discontinued

  • CAS Number: 868273-90-9
  • MF: C21H34N4O4S
  • MW: 438.584
  • Catalog: Cathepsin
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nidufexor

Nidufexor is a farnesoid X receptor (FXR) agonist[1].

  • CAS Number: 1773489-72-7
  • MF: C27H22ClN3O4
  • MW: 487.93
  • Catalog: FXR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 781.1±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 426.2±32.9 °C

Carbonic anhydrase inhibitor 14

Carbonic anhydrase inhibitor 14 (Compound 8b) is a carbonic anhydrase (CA) inhibitor with Ki values of 1203, 99.7, 9.4 and 27.7 nM against hCA I, hCA II, hCA IX and hCA XII, respectively. Carbonic anhydrase inhibitor 14 can also inhibit CDK2 with an IC50 of 20.3 μM. Carbonic anhydrase inhibitor 14 shows antitumor activity[1].

  • CAS Number: 2410402-75-2
  • MF: C18H17N7O2S
  • MW: 395.44
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3",8"-Binaringenin

Tetrahydroamentoflavone (Amentoflavanone) is a potent xanthine oxidase (XO) inhibitor. Tetrahydroamentoflavone has inhibitory activity for XO with IC50 and Ki values of 92 nM and 0.982 μM, respectively. Tetrahydroamentoflavone can be used for the research of inflammatory disorders and gout[1].

  • CAS Number: 48236-96-0
  • MF: C30H22O10
  • MW: 542.490
  • Catalog: Xanthine Oxidase
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 932.8±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 314.3±27.8 °C

BMS-309403

BMS-309403 is a potent, selective and cell-permeable inhibitor of fatty acid binding protein 4 (FABP4) with a Ki of less than 2 nM.

  • CAS Number: 300657-03-8
  • MF: C31H26N2O3
  • MW: 474.550
  • Catalog: FABP
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 657.5±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 351.4±31.5 °C

Ramipril

Ramipril is an angiotensin-converting enzyme (ACE) inhibitor with IC50 of 5 nM.Target: ACERamipril is an angiotensin-converting enzyme (ACE) inhibitor with IC50 of 5 nM [1]. Ramipril enhances the activity of ACE-associated CK2 and the phosphorylation of ACE Ser1270 in cultured endothelial cells, but is unable to activate JNK or stimulate the nuclear accumulation of c-Jun in endothelial cells expressing a S1270A ACE mutant or in ACE-deficient cells. Prolonged Ramipril treatment increases ACE expression in primary cultures of human endothelial cells and in vivo (mouse lung), which can be prevented by pretreatment with the JNK inhibitor SP600125 [2].Chronic in vivo administration of Ramipril to rats at a dosage that has similar hypotensive effects in vitro HUVECs significantly reduces the rate of LPS-induced apoptosis compared to the other ACE inhibitors, which contrasts with the apoptosis effect in vitro [3]. Ramipril inhibits systolic blood pressure (SBP) with IC50 of 1.97 mg/kg in spontaneously hypertensive rats (SHR). When in combination with AT1-receptor blockade by candesartan-cilexetil increases SBP reduction synergistically rather than additively [4].

  • CAS Number: 87333-19-5
  • MF: C23H32N2O5
  • MW: 416.511
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 616.2±55.0 °C at 760 mmHg
  • Melting Point: 106-108°C
  • Flash Point: 326.4±31.5 °C

Sofigatran

Sofigatran (MCC-977) is an orally active factor IIa (thrombin) inhibitor, acts as an anticoagulant. Sofigatran is used for the research of cardiovascular disease[1].

  • CAS Number: 187602-11-5
  • MF: C24H44N4O4S
  • MW: 484.69600
  • Catalog: Thrombin
  • Density: 1.118
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ACT001

ACT001 is an orally active PAI-1 inhibitor by inhibiting the phosphorylation of PI3K and AKT. ACT001 inhibits the phosphorylation of STAT3 and PD-L1 expression by directly binding to STAT3. ACT001, a fumarate salt form of DMAMCL (a prodrug of Micheliolide), can cross the blood-brain barrier. ACT001 has potent anti-glioblastoma (GBM) activity and immunomodulatory effects[1][2].

  • CAS Number: 1582289-91-5
  • MF: C21H31NO7
  • MW: 409.47
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Daclatasvir (BMS-790052)

Daclatasvir is a potent HCV NS5A protein inhibitor, with mean EC50 values of 50 and 9 pM against genotype 1a and 1b replicons, respectively.

  • CAS Number: 1009119-64-5
  • MF: C40H50N8O6
  • MW: 738.875
  • Catalog: HCV
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 1071.2±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 601.7±34.3 °C

Retinoic acid-d6

Retinoic acid-d6 is the deuterium labeled Retinoic acid[1]. 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. Retinoic acid acts as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha[2][3][4][5][6][7].

  • CAS Number: 2483831-72-5
  • MF: C20H22D6O2
  • MW: 306.47
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ALDH3A1-IN-2

ALDH3A1-IN-2 (Compound 19) is a potent inhibitor of ALDH3A1 with an IC50 of 1.29 μM. Aldehyde dehydrogenases (ALDHs) are overexpressed in various tumor types including prostate cancer. ALDH3A1-IN-2 has the potential for the research of cancer diseases[1].

  • CAS Number: 374635-48-0
  • MF: C11H14N2O3
  • MW: 222.24
  • Catalog: Aldehyde Dehydrogenase (ALDH)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

biochanin A

Biochanin A is a naturally occurring fatty acid amide hydrolase (FAAH) inhibitor, which inhibits FAAH with IC50s of 1.8, 1.4 and 2.4 μM for mouse, rat, and human FAAH, respectively.

  • CAS Number: 491-80-5
  • MF: C16H12O5
  • MW: 284.263
  • Catalog: FAAH
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 518.6±50.0 °C at 760 mmHg
  • Melting Point: 210-213 °C(lit.)
  • Flash Point: 198.3±23.6 °C

fenvalerate

Fenvalerate is a potent protein phosphatase 2B (calcineurin) inhibitor with an IC50 of 2-4 nM for PP2B-Aα. Fenvalerate is a pyrethroid ester insecticide and acaricide[1].

  • CAS Number: 51630-58-1
  • MF: C25H22ClNO3
  • MW: 419.900
  • Catalog: Bacterial
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 538.9±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 279.7±30.1 °C

β-Tocopherol

β-Tocopherol is an analogue of vitamin E, exhibits antioxidant properties. β-Tocopherol can inhibit tyrosinase activity and melanin synthesis. β-Tocopherol also can prevent the inhibition of cell growth and of PKC activity caused by d-alpha-tocopherol[1][2][3].

  • CAS Number: 16698-35-4
  • MF: C28H48O2
  • MW: 416.68000
  • Catalog: Tyrosinase
  • Density: 0.933g/cm3
  • Boiling Point: 516.267°C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 204.683°C

ML-030

ML-030 is a potent PDE4 inhibitor, with IC50 of 6.7 nM, 12.9 nM, 48.2 nM, 37.2 nM, 452 nM and 49.2 nM for PDE4A, PDE4A1, PDE4B1, PDE4B2, PDE4C1,and PDE4D2, respectively.

  • CAS Number: 1013750-77-0
  • MF: C20H20N4O4S
  • MW: 412.462
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 633.2±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 336.7±34.3 °C

Homo Sildenafil-d5

Homo Sildenafil-d5 is the deuterium labeled Homo Sildenafil. Homo Sildenafil, an analog of Sildenafil, acts as a phosphodiesterase inhibitor[1][2].

  • CAS Number: 1216711-61-3
  • MF: C23H27D5N6O4S
  • MW: 493.63
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Stigmasterol glucoside

Stigmasterol glucoside is a sterol isolated from P. urinaria with high antioxidant and anti-inflammatory activities[1], act as an inhibitor of 5α-reductase with an IC50 of 27.2 µM[2].

  • CAS Number: 19716-26-8
  • MF: C35H58O6
  • MW: 574.831
  • Catalog: 5 alpha Reductase
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 673.6±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 361.2±31.5 °C

C12 NBD-SPHINGOMYELIN

C12 NBD sphingomyelin is an active derivative of sphingomyelin (HY-113498) that is tagged with fluorescent C12 nitrobenzoxadiazole (C12 NBD). C12 NBD sphingomyelin can be used as a sphingomyelinase substrate for studying the metabolism and transport of sphingomyelins (Ex=470 nm, Em=525 nm)[1].

  • CAS Number: 254117-01-6
  • MF: C41H73N6O9P
  • MW: 825.027
  • Catalog: Phospholipase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tectol

Tectol, isolated from Lippia sidoides, exhibits significant activity against human leukemia cell lines HL60 and CEM[1]. Tectol is a farnesyltransferase (FTase) inhibitor with IC50s of 2.09 and 1.73 μM for human and T. brucei FTase. Tectol inhibits drug-resistant strain of P. falciparum (FcB1) with an IC50 of 3.44 μM[1][2].

  • CAS Number: 24449-39-6
  • MF: C30H26O4
  • MW: 450.52500
  • Catalog: Farnesyl Transferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

chymostatin

Chymostatin is a potent cathepsin G inhibitor. Chymostatin inhibits fungal growth when combined with other pepsin inhibitors. Chymostatin can be used for acute lung injury and pancreatitis research[1].

  • CAS Number: 9076-44-2
  • MF: C31H41N7O6
  • MW: 607.701
  • Catalog: Cathepsin
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 276-278℃
  • Flash Point: N/A

licopyranocoumarin

Licopyranocoumarin is an isoflavonoid that shows CYP3A4 inhibitory activity with an IC50 of 32 μM. Licopyranocoumarin has potent neuroprotective activities[1].

  • CAS Number: 117038-80-9
  • MF: C21H20O7
  • MW: 384.37900
  • Catalog: Cytochrome P450
  • Density: 1.397g/cm3
  • Boiling Point: 675.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 242.9ºC

CAY10581

CAY10581, a pyranonaphthoquinone derivative, is a highly specific and reversible uncompetitive IDO Inhibitor with an IC50 of 55 nM[1][2].

  • CAS Number: 1018340-07-2
  • MF: C22H21NO4
  • MW: 363.406
  • Catalog: Indoleamine 2,3-Dioxygenase (IDO)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 548.8±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 285.7±30.1 °C

Indirubin-3'-monoxime

Indirubin-3'-monoxime is a potent GSK-3β inhibitor, and weakly inhibits 5-Lipoxygenase, with IC50s of 22 nM and 7.8-10 µM, respectively; Indirubin-3'-monoxime also shows inhibitory activities against CDK5/p25 and CDK1/cyclin B, with IC50s of 100 and 180 nM.

  • CAS Number: 160807-49-8
  • MF: C16H11N3O2
  • MW: 277.277
  • Catalog: 5-Lipoxygenase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 532.2±50.0 °C at 760 mmHg
  • Melting Point: 241 °C
  • Flash Point: 275.7±30.1 °C

Manumycin A

Manumycin A is an antibiotic. Manumycin A acts as a selective, competitive inhibitor of protein farnesyltransferase (FTase) with respect to farnesylpyrophosphate (Ki =1.2 μM), and as a noncompetitive inhibitor with respect to the Ras protein. Manumycin A induces apoptosis and exerts antitumor activity[1] [2][3].

  • CAS Number: 52665-74-4
  • MF: C31H38N2O7
  • MW: 550.643
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 863.6±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 476.1±34.3 °C

3-O-Acetyl-11-hydroxy-beta-boswellic acid

3-O-Acetyl-11-hydroxy-beta-boswellic acid is a potent 5-lipoxygenase (5-LO) inhibitor[1].

  • CAS Number: 146019-25-2
  • MF: C32H50O5
  • MW: 514.746
  • Catalog: 5-Lipoxygenase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 160-162 °C
  • Flash Point: N/A

CORT 118335

CORT 118335 (Miricorilant, C118335) is a novel potent, selective, non-steroidal glucocorticoid receptor (GR) antagonist with Ki of 8 nM, shows modest affinity for MR.

  • CAS Number: 1400902-13-7
  • MF: C24H23F3N2O2
  • MW: 428.447
  • Catalog: Glucocorticoid Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A