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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Microcystin-LR

Microcystin-LR is a potent inhibitor of type 1 and type 2A protein phosphatases (PP1 and PP2A), with IC50s of 1.7 nM and 0.04 nM, respectively. Sequence: Ala-D-Ala-Leu-D-{Bas}-Arg-{Oaa}-D-{Ggu}.

  • CAS Number: 101043-37-2
  • MF: C49H74N10O12
  • MW: 995.172
  • Catalog: Peptides
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: 11 °C

acetazolamide

Acetazolamide is a carbonic anhydrase (CA) IX inhibitor with an IC50 of 30 nM for hCA IX[1]. Diuretic effects[4].

  • CAS Number: 59-66-5
  • MF: C4H6N4O3S2
  • MW: 222.245
  • Catalog: Bacterial
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 256-261°C
  • Flash Point: N/A

NP-313

NP-313 is a potent antithrombotic agent that inhibits platelet aggregation and activation. NP-313 has dual inhibition of thromboxane A 2 synthesis and selective inhibition of SOCC-mediated Ca2+ inward flow[1].

  • CAS Number: 5397-78-4
  • MF: C12H8ClNO3
  • MW: 249.65000
  • Catalog: Thrombin
  • Density: 1.44g/cm3
  • Boiling Point: 427.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 212.5ºC

Amastatin · HCl

Amastatin hydrochloride is a slow, tight binding, competitive aminopeptidase (AP) inhibitor with Ki values of 0.26 nM, 30 nM, 52 nM for Aeromonas aminopeptidase, cytosolic leucine aminopeptidase, microsomal aminopeptidase[1].

  • CAS Number: 100938-10-1
  • MF: C21H39ClN4O8
  • MW: 511.009
  • Catalog: Bacterial
  • Density: N/A
  • Boiling Point: 795.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 434.7ºC

Aminopeptidase N Ligand (CD13) NGR peptide

Aminopeptidase N Ligand (CD13) NGR peptide is a polypeptide targeting CD13 and can be used as a carrier to mediate intracellular transmission. Aminopeptidase N Ligand (CD13) NGR peptide is often used in cancer research[1][2].

  • CAS Number: 760947-20-4
  • MF: C20H34N10O8S2
  • MW: 606.68
  • Catalog: Aminopeptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Quinidine sulfate dihydrate

Quinidine sulfate dihydrate is a potent and selective inhibitor of cytochrome P450db and inhibits amphetamine metabolism in vivo[1]. Quinidine sulfate dihydrate enhances the cytotoxicity of vincristine (VCR) in tumor cells and especially in VCR-resistant sublines of P388 leukemia (P388/VCR) and human myelogenous leukemia[2].

  • CAS Number: 6591-63-5
  • MF: C20H24N2O2.1/2H2O4S.H2O
  • MW: 782.943
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: 992.5ºC at 760 mmHg
  • Melting Point: 212-214 °C (dec.)(lit.)
  • Flash Point: 554ºC

Hydroxyevodiamine

Hydroxyevodiamine (Rhetsinine) inhibits aldose reductase with an IC50 value of 24.1 μM[1].

  • CAS Number: 1238-43-3
  • MF: C19H17N3O2
  • MW: 319.357
  • Catalog: Aldose Reductase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 633.4±55.0 °C at 760 mmHg
  • Melting Point: 190 °C
  • Flash Point: 336.9±31.5 °C

ER 50891

ER-50891 is a potent antagonist of retinoic acid receptor α(RARα). ER-50891 significantly attenuates ATRA's inhibitive effects on BMP 2-induced osteoblastogenesis[1].

  • CAS Number: 187400-85-7
  • MF: C29H24N2O2
  • MW: 432.51300
  • Catalog: RAR/RXR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Plantainoside D

Plantainoside D shows ACE inhibitory activity with IC50 2.17 mM[1]. And plantainoside D is a promising IKK-β inhibitor[2].

  • CAS Number: 147331-98-4
  • MF: C29H36O16
  • MW: 640.59
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-[(1S,2R,4S)-4-carbamoyl-2-[(7-methyl-4,5,6,8-tetrahydropyrido[4,3-e][1,3]thiazine-2-carbonyl)amino]cyclohexyl]-N'-(5-chloropyridin-2-yl)oxamide,hydrochloride

Edoxaban (DU-176b) hydrochloride is an orally active, highly potent, selective, and direct Factor Xa (FXa) inhibitor with Ki values of 0.561 and 2.98 nM for free human FXa and prothrombinase. Edoxaban hydrochloride exhibits more than 10,000-fold selectivity over other coagulation proteases. Edoxaban hydrochloride can be used for preventing thromboembolic disease research[1].

  • CAS Number: 480448-29-1
  • MF: C23H29Cl2N7O4S
  • MW: 570.49200
  • Catalog: Factor Xa
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

7-Hydroxy-4-(trifluoromethyl)coumarin

4-(Trifluoromethyl)umbelliferone is fluorescent probe substrate for rat hepatic cytochrome P450 enzymes[1].

  • CAS Number: 575-03-1
  • MF: C10H5F3O3
  • MW: 230.140
  • Catalog: Cytochrome P450
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 311.4±42.0 °C at 760 mmHg
  • Melting Point: 178-180 °C(lit.)
  • Flash Point: 142.2±27.9 °C

hCAIX/XII-IN-2

hCAIX/XII-IN-2 (compound 6a) is a potent and selective hCAIX and hCAXIIinhibitor with Ki values of >10000, >10000, 30.0, 3.6 nM for hCAI, hCAII, hCAIX and hCAXII, respectively[1].

  • CAS Number: 2414629-82-4
  • MF: C19H14N2O4
  • MW: 334.33
  • Catalog: Carbonic Anhydrase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Trandolaprilat Monohydrate

Trandolaprilate hydrate is a potent angiotensin-converting enzyme (ACE) inhibitor. Trandolaprilate hydrate partially inhibits angiotensin-I-mediated c-fos induction. Trandolaprilate is main bioactive metabolite of Trandolapril. Trandolaprilate shows high lipophilicity[1][2].

  • CAS Number: 951393-55-8
  • MF: C22H32N2O6
  • MW: 420.49900
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Balicatib

Balicatib(AAE-581) is a potent and selective inhibitor of cathepsin K; 10-100 fold more potent in cell-based enzyme occupancy assays than against cathepsin B, L, and S.IC50 value:Target: cathepsin KThe cathepsin K inhibitor AAE-581 (balicatib) as the most advanced of them passed Phase II clinical trials in 2005. Eighty adult female Macaca fascicularis underwent bilateral ovariectomies and were dosed twice daily by oral gavage with balicatib at 0, 3, 10, and 50 mg/kg for 18 months (groups O, L, M, H, respectively). Approximately 1 month after treatment initiation, the 50 mg/kg dose was decreased to 30 mg/kg. Twenty animals underwent sham-ovariectomies (group S). Bone mass was measured at 3-6 month intervals. At 18 months, vertebra and femur were collected for histomorphometry.

  • CAS Number: 354813-19-7
  • MF: C23H33N5O2
  • MW: 411.540
  • Catalog: Cathepsin
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 687.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 369.5±31.5 °C

K 579

K579 is a potent and orally active dipeptidyl peptidase IV inhibitor. K579 inhibits the blood glucose elevation. K579 increases the plasma insulin and active forms of glucagon-like peptide-1 (GLP-1). K579 has the potential for the research of diabetic[1].

  • CAS Number: 440100-64-1
  • MF: C17H24N6O
  • MW: 328.41
  • Catalog: Dipeptidyl Peptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FXR/TGR5 agonist 1

FXR/TGR5 agonist 1 has agonist action on FXR and TGR5, and can be used for the treatment of fatty liver disease.

  • CAS Number: 2677689-72-2
  • MF: C31H32ClN3O3
  • MW: 530.06
  • Catalog: GPCR19
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Momordicoside A

Momordicoside A is isolated from Momordica charantia L. Momordicoside A has the inhibitory effect on protein tyrosine phosphatase (PTP1B)[1].

  • CAS Number: 75801-95-5
  • MF: C42H72O15
  • MW: 817.012
  • Catalog: Phosphatase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 969.3±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 540.0±34.3 °C

Ganoderic acid Df

Ganoderic acid Df is a lanostane-type triterpenoid, that can be isolated from the fruiting body of Ganoderma lucidum. Ganoderic acid Df potently inhibits aldose reductase, with an IC50 of 22.8 ± 0.6 μM[1].

  • CAS Number: 1352033-73-8
  • MF: C30H44O7
  • MW: 516.67
  • Catalog: Aldose Reductase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Elasnin

Elasnin is a selective granulocyte elastase inhibitor. Elasnin is almost ineffective for pancreatic elastase, trypsin, chymotrypsin, thermolysin and papain[1].

  • CAS Number: 68112-21-0
  • MF: C24H40O4
  • MW: 392.57
  • Catalog: Elastase
  • Density: 1.001g/cm3
  • Boiling Point: 521ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 166.6ºC

metyrapone

Metyrapone is an inhibitor of cytochrome P450-mediated ω/ω-1 hydroxylase activity and CYP11B1.Target: CYP11B1Metyrapone is a drug used in the diagnosis of adrenal insufficiency and occasionally in the treatment of Cushing's syndrome (hypercortisolism). Metyrapone blocks cortisol synthesis by reversibly inhibiting steroid 11β-hydroxylase. This stimulates ACTH secretion, which in turn increases plasma 11-Deoxycortisol levels.

  • CAS Number: 54-36-4
  • MF: C14H14N2O
  • MW: 226.274
  • Catalog: Autophagy
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 384.4±22.0 °C at 760 mmHg
  • Melting Point: 53-56ºC
  • Flash Point: 189.3±28.8 °C

Ethoxzolamide

Ethoxzolamide is a carbonic anhydrase inhibitor with Ki of 1 nM.

  • CAS Number: 452-35-7
  • MF: C9H10N2O3S2
  • MW: 258.31700
  • Catalog: Carbonic Anhydrase
  • Density: 1.47g/cm3
  • Boiling Point: 464.9ºC at 760mmHg
  • Melting Point: 190-193ºC(lit.)
  • Flash Point: 235ºC

Ledipasvir

Ledipasvir is an inhibitor of the hepatitis C virus NS5A, with EC50s of 34 pM and 4 pM against genotype 1a and 1b replicon, respectively.

  • CAS Number: 1256388-51-8
  • MF: C49H54F2N8O6
  • MW: 889.000
  • Catalog: HCV
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BIIB021

BIIB021 is an orally available, fully synthetic inhibitor of HSP90 with Ki and EC50 of 1.7 nM and 38 nM, respectively.

  • CAS Number: 848695-25-0
  • MF: C14H15ClN6O
  • MW: 318.762
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 588.5±60.0 °C at 760 mmHg
  • Melting Point: 192-193℃
  • Flash Point: 309.7±32.9 °C

Glycerol trimyristate

Trimyristin, an active molluscicidal component of Myristica fragrans Houtt, significantly inhibits acetylcholinesterase (AChE), acid and alkaline phosphatase (ACP/ALP) activities in the nervous tissue of Lymnaea acuminata. IC50s of Trimyristin against AChE, ACP, and ALP are 0.11, 0.16 and 0.18 mM, respectively[1].

  • CAS Number: 555-45-3
  • MF: C45H86O6
  • MW: 723.161
  • Catalog: Phosphatase
  • Density: 0.9±0.1 g/cm3
  • Boiling Point: 703.5±27.0 °C at 760 mmHg
  • Melting Point: 56-57 °C(lit.)
  • Flash Point: 270.9±23.8 °C

Anticancer agent 143

Anticancer agent 143 (compound 369) is a dual PTPN2/PTP1B inhibitor with IC50 values <2.5 nM. Anticancer agent 143 can be used in cancer research[1].

  • CAS Number: 2948339-38-4
  • MF: C19H15BrF2N3O6PS2
  • MW: 594.34
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Olprinone

Olprinone(Loprinone) is a selective phosphodiesterase 3 (PDE3) inhibitor. IC50 value:Target: PDE3Olprinone is used as cardiotonic agent with positive inotropic and vasodilating effects. Olprinone has been reported to improve microcirculation and attenuate inflammation. Olprinone is often used to increase cardiac output after cardiopulmonary bypass (CPB). Olprinone was infused at a rate of 0.2 μg/kg/min when weaning from CPB was started. Olprinone has also shown potent antioxidative and anti-inflammatory effects in the meconium-induced oxidative lung injury.

  • CAS Number: 106730-54-5
  • MF: C14H10N4O
  • MW: 250.255
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: >300ºC
  • Flash Point: N/A

SDZ-MKS 492

SDZ-MKS 492 (MKS 492) is a selective type III isozyme inhibitor of cyclic nucleotide phosphodiesterase, effective in allergic bronchoconstriction and platelet activating factor (PAF) or LTB4-induced inflammatory reactions in animals[1].

  • CAS Number: 114606-56-3
  • MF: C20H27N5O6
  • MW: 433.46
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DHODH-IN-3

DHODH-IN-3 (compound 3) is a potent inhibitor of Human Dihydroorotate Dehydrogenases (HsDHODH) with an IC50 value of 261 nM. DHODH-IN-3 binds to the the ubiquinone binding cavities in DHODH with a Kiapp of 32 nM. DHODH-IN-3 has the potential for malaria treatment[1].

  • CAS Number: 1148126-04-8
  • MF: C17H13ClN2O2
  • MW: 312.75
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Isoglycycoumarin

Isoglycycoumarin is a flavonoid isolated from the roots of Glycyrrhiza uralensis. Isoglycycoumarin is a highly selective probe for human cytochrome P450 2A6 (CYP2A6)[1][2].

  • CAS Number: 117038-82-1
  • MF: C21H20O6
  • MW: 368.38000
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

edoxaban

Edoxaban(DU-176) is an oral factor Xa (FXa) inhibitor in clinical development for stroke preventionIC50 Value:Target: factor XaEdoxaban is an oral factor Xa (FXa) inhibitor in clinical development for stroke prevention in patients with atrial fibrillation, an elderly population that frequently receives aspirin (ASA) and/or nonsteroidal anti-inflammatory drugs for concurrent illnesses[1].in vitro: Edoxaban PK was not affected by concomitant low-dose ASA or naproxen, but high-dose ASA increased systemic exposure of edoxaban by approximately 30%. The effects of edoxaban on prothrombin time, activated partial thromboplastin time, international normalized ratio, anti-FXa, and intrinsic FXa activity were not influenced by administration with ASA or naproxen. Inhibition of platelet aggregation by high-dose ASA, low-dose ASA, or naproxen was not affected by edoxaban[1].in vivo: Forty-eight subjects, aged 18 to 45 years, received either edoxaban 60 mg once daily × 7 days (n = 24) or digoxin 0.25 mg twice daily × 2 days and once daily × 5 days (n = 24) and then concomitantly for 7 days. Serial blood and urine samples were collected for digoxin and edoxaban concentrations on days 7 and 14. Serial coagulation assays were measured for edoxaban on days 7 and 14. Edoxaban PK parameters demonstrated mild increases in area under the curve and peak concentrations of 9.5% and 15.6%, respectively[2],Clinical trial: Pharmacokinetics, biotransformation, and mass balance of edoxaban, a selective, direct factor Xa inhibitor, in humans was reported[3].

  • CAS Number: 480449-70-5
  • MF: C24H30ClN7O4S
  • MW: 548.057
  • Catalog: Factor Xa
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A