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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MtTMPK-IN-4

MtTMPK-IN-4 (compound 2), a para-piperidine, is a potent mycobacterium tuberculosis thymidylate kinase (MtTMPK) inhibitor with an IC50 of 6.1 μM. MtTMPK-IN-4 is a potent tyrosinase inhibitor. MtTMPK-IN-4 is a potent antibacterial agent[1][2].

  • CAS Number: 2225889-49-4
  • MF: C23H25N3O3
  • MW: 391.46
  • Catalog: Bacterial
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1H-Purine-2,6-dione,7-[2-[[2-(3,4-dihydroxyphenyl)-2-hydroxyethyl]amino]ethyl]-3,7-dihydro-1,3-dimethyl-,hydrochloride (1:1)

Theodrenaline hydrochloride is a cardiac stimulant, also acts as an anti-hypotensive agent together with Cafedrine.

  • CAS Number: 2572-61-4
  • MF: C17H22ClN5O5
  • MW: 411.84
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: 723.6ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 391.4ºC

GSK3494245

GSK3494245 (DDD01305143) is a potent, orally active, and selective inhibitor of the chymotrypsin-like activity of the parasite proteasome binding in a site sandwiched between the β4 and β5 subunits (IC50=0.16 μM for WT L. donovani proteasomes). GSK3494245 moderately inhibits chymotrypsin-like activity of human proteasome (IC50: purified 26S=13 µM; enriched THP-1 extracts IC50=40µM). GSK3494245 exhibits attractive biological and biosafety properties[1][2].

  • CAS Number: 2080410-41-7
  • MF: C21H23FN6O2
  • MW: 410.44
  • Catalog: Proteasome
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NCGC00249987

NCGC00249987 is a highly selective and allosteric Tyr phosphatase activity of Eya2 inhibitor with IC50s of 3 μM and 6.9 μM for Eya2 ED and MBP-Eya2 FL. NCGC00249987 specifically targets migration, invadopodia formation, and invasion of lung cancer cells[1].

  • CAS Number: 1384864-80-5
  • MF: C16H11FN4O2S
  • MW: 342.35
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

8-Prenylluteone

8-Prenylluteone is a HIV-1 protease inhibitor, with an IC50 of 4 μM[1].

  • CAS Number: 125002-91-7
  • MF: C25H26O6
  • MW: 422.47
  • Catalog: HIV Protease
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 668.9±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 229.3±25.0 °C

BRD9500

BRD9500 is an orally active phosphodiesterases 3 (PDE3) inhibitor with IC50s of 10 and 27 nM for PDE3A and PDE3B, respectively. Antitumor activity[1].

  • CAS Number: 1630760-75-6
  • MF: C15H18FN3O2
  • MW: 291.32
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AG-120

IDH1 Inhibitor 8 (91) is isocitrate dehydrogenase 1 (IDH1) inhibitor. IDH1 Inhibitor 8 can be used for the research of cancer[1].

  • CAS Number: 1448346-63-1
  • MF: C28H22ClF3N6O3
  • MW: 582.96
  • Catalog: Isocitrate Dehydrogenase (IDH)
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 854.3±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 470.4±34.3 °C

Tanomastat

Tanomastat (BAY 12-9566) is an orally bioavailable, non-peptidic biphenyl matrix metalloproteinases (MMPs) inhibitor with a Zn-binding carboxyl group. The Ki values are 11, 143, 301, and 1470 nM for MMP-2, MMP-3, MMP-9, MMP-13 respectively. Tanomastat shows anti-invasive and antimetastatic activity in several experimental tumor models[1][2][3].

  • CAS Number: 179545-77-8
  • MF: C23H19ClO3S
  • MW: 410.91300
  • Catalog: MMP
  • Density: 1.33g/cm3
  • Boiling Point: 620.1ºC at 760 mmHg
  • Melting Point: 110-110.5ºC
  • Flash Point: 328.8ºC

JCP174

JCP174 is an inhibitor of palmitoyl protein thioesterase-1 (TgPPT1), a depalmitoylase in the parasite T. gondii[1]. JCP174 is also an inhibitor of porcine pancreatic elastase and human leukocyte elastase[2][3].

  • CAS Number: 126062-19-9
  • MF: C12H12ClNO3
  • MW: 253.682
  • Catalog: Elastase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 463.4±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 234.1±28.7 °C

R 80123

R 80123 is the Z-isomer of R 79595, is also a highly selective phosphodiesterase inhibitor. The fuction is similar to R 80122 (HY-100615, Revizinone).In vivo: The administration of Revizinone improved the haemodynamic profile with an increase in cardiac output, a decrease in systemic vascular resistance and a stable heart rate and mean arterial blood pressure. [1] With regard to reconstitution of contractility and cardiac function Revizinone (E-isomer) is 10 fold more potent than R 79595 and nearly 100 fold more potent than R 80123 (Z-isomer). [2] Revizinone significantly increases global LV function and systolic wall thickening in ischemic areas at doses greater than or equal to 0.16 mg/kg i.v. [3]

  • CAS Number: 133718-30-6
  • MF: C26H29N5O3
  • MW: 459.540
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aureusidin

Aureusidin is an aurone with high antioxidant and lipoxygenase inhibitory activity. Aureusidin also shows anti-inflammatory effects[1].

  • CAS Number: 38216-54-5
  • MF: C15H10O6
  • MW: 286.23600
  • Catalog: 5-Lipoxygenase
  • Density: 1.708g/cm3
  • Boiling Point: 628.6ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 244.3ºC

YM17E

YM17E is an inhibitor of acyl CoA:cholesterol acyltransferase (ACAT), with IC50 of 44 nM in rabbit liver microsomes in vitro.

  • CAS Number: 124900-72-7
  • MF: C40H56N6O2
  • MW: 652.912
  • Catalog: Acyltransferase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 862.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 475.5±34.3 °C

2-(3,4-dihydroxyphenyl)-5,6,7-trihydroxychromen-4-one

6-Hydroxyluteolin (Compound 17) is a flavonoid compound. 6-Hydroxyluteolin has an inhibitory effect on aldose reductase (AR) [1].

  • CAS Number: 18003-33-3
  • MF: C15H10O7
  • MW: 302.23600
  • Catalog: Aldose Reductase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CB2R/FAAH modulator-1

CB2R/FAAH modulator-1 is a cannabinoid type 2 receptor (CB2R) full agonist with Kis of 14.8 nM and 241.3 nM for CB2R and CB1R, respectively. CB2R/FAAH modulator-1 is a fatty acid amide hydrolase (FAAH) inhibitor with an IC50 of 4 μM. CB2R/FAAH modulator-1 decreases pro-inflammatory and increases anti-inflammatory cytokines production[1].

  • CAS Number: 928892-60-8
  • MF: C24H27NO2
  • MW: 361.48
  • Catalog: Cannabinoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Opevesostat

Opevesostat is a cholesterol side-chain cleavage enzyme (CYP11A1) inhibitor[1].

  • CAS Number: 2231294-96-3
  • MF: C21H26N2O5S
  • MW: 418.51
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Skp2 inhibitor 1

Skp2 inhibitor 1 (compound 14i) is a potent and selective Skp2 inhibitor against the Skp2-Cks1 interaction with an IC50 of 2.8 μM. Skp inhibitor 1 exhibits anticancer activity[1].

  • CAS Number: 2760612-63-1
  • MF: C23H23ClN4O
  • MW: 406.91
  • Catalog: E1/E2/E3 Enzyme
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

mvt 101

Mvt-101 is a hexapeptide-based inhibitor of HIV-1 protease. Mvt-101 is also reduced-peptide-bond inhibitor. Mvt-101 inhibits reproduction of the HIV virus by blocking protease action[1].

  • CAS Number: 125552-93-4
  • MF: C35H67N11O8
  • MW: 769.97500
  • Catalog: HIV Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fosinopril

Fosinopril (SQ28555) is the ester prodrug of an angiotensin-converting enzyme (ACE) inhibitor with the IC50 value of 0.18 μM[1]. Fosinopril demonstrates a non-competitive inhibition effect on ACE activity with a Ki value of 1.675 μM[2].

  • CAS Number: 98048-97-6
  • MF: C30H46NO7P
  • MW: 563.66300
  • Catalog: Apoptosis
  • Density: 1.173 g/cm3
  • Boiling Point: 705.7ºC at 760 mmHg
  • Melting Point: 149-153ºC
  • Flash Point: 380.6ºC

SKF107457

SKF107457 is an HIV-1 protease inhibitor that can be used in AIDS research[1][2].

  • CAS Number: 126333-28-6
  • MF: C29H47N5O7
  • MW: 577.71300
  • Catalog: HIV Protease
  • Density: 1.154g/cm3
  • Boiling Point: 897.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 496.8ºC

MGAT2-IN-2

MGAT2-IN-2 is a potent and selective acyl CoA:monoacylglycerol acyltransferase 2 (MGAT2) inhibitor with an IC50 of 3.4 nM.

  • CAS Number: 1710630-11-7
  • MF: C26H21F5N4O4S
  • MW: 580.53
  • Catalog: Acyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lovastatin hydroxy acid sodium

Lovastatin hydroxy acid sodium (Mevinolinic acid sodium) is a highly potent inhibitor of HMG-CoA reductase with a Ki of 0.6 nM[1].

  • CAS Number: 75225-50-2
  • MF: C24H37NaO6
  • MW: 444.537
  • Catalog: HMG-CoA Reductase (HMGCR)
  • Density: N/A
  • Boiling Point: 602.3ºC at 760 mmHg
  • Melting Point: 154-160ºC
  • Flash Point: 199.1ºC

8α-(2-Methylacryloyloxy)hirsutinolide 13-O-acetate

8α-(2-Methylacryloyloxy)-hirsutinolide-13-O-acetate is an irreversible CYP2A6 inhibitor with IC50s of 8.64 μM and 22.3 μM with pre-incubation and co-incubaition, respectively. 8α-(2-Methylacryloyloxy)-hirsutinolide-13-O-acetate also inhibits MAO-A and MAO-B with IC50s of 60.2 and 38.6 μM, respectively[1].

  • CAS Number: 67667-71-4
  • MF: C21H26O8
  • MW: 406.42600
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KZR-504

KZR-504 is a highly selective and orally active inhibitor of immunoproteasome low molecular mass polypeptide 2 (LMP2), with IC50s of 51 nM, 4.274 μM for LMP2 and LMP7, respectively.

  • CAS Number: 1629052-78-3
  • MF: C21H23N3O6
  • MW: 413.42
  • Catalog: Proteasome
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Quercetin-3-gentiobioside

Quercetin 3-gentiobioside is isolated from A. iwayomogi, AR and AGE formation inhibitor, demonstrates biological activities against Aldose reductase (AR) and the formation of advanced glycation endproducts (AGEs)[1].

  • CAS Number: 7431-83-6
  • MF: C27H30O17
  • MW: 626.517
  • Catalog: Aldose Reductase
  • Density: 1.9±0.1 g/cm3
  • Boiling Point: 1033.2±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 340.6±27.8 °C

Berotralstat dihydrochloride

Berotralstat dihydrochloride is a low toxicity, effective, highly specific, second-generation, synthetic and orally active plasma kallikrein inhibitor used for the research of hereditary angioedema (HAE) attacks. Berotralstat dihydrochloride works by blocking the enzymatic activity of plasma kallikrein in releasing bradykinin, the major biologic peptide that promotes swelling and pain associated with attacks of HAE[1][2].

  • CAS Number: 1809010-52-3
  • MF: C30H28Cl2F4N6O
  • MW: 635.48
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Samatasvir

Samatasvir (IDX719) is a highly potent, selective inhibitor of HCV NS5A that effectively inhibits HCV genotype 1-5 replicons with EC50 of 2-24 pM; also retains full activity in the presence of HIV and hepatitis B virus (HBV) antivirals; demonstrates an overall additive effect when combined with IFN-α, ribavirin, representative HCV protease, and nonnucleoside polymerase inhibitors or the nucleotide prodrug IDX184. HCV Infection Phase 2 Clinical

  • CAS Number: 1312547-19-5
  • MF: C47H48N8O6S2
  • MW: 885.064
  • Catalog: HCV
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FM26

FM26 (compound 25) is a potent and allosteric retinoic acid receptor-related orphan receptor γt (RORγt) inverse agonists with an IC50 of 264 nM. FM26 has a distinct isoxazole chemotype and effectively reduces IL-17a mRNA production in EL4 cells[1].

  • CAS Number: 2407981-35-3
  • MF: C22H15ClF3N3O3
  • MW: 461.82
  • Catalog: ROR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Diaplasinin

Diaplasinin (PAI-749) is a plasminogen activator inhibitor-1 (PAI-1) inhibitor with IC50 of 295 nm. Antithrombotic efficacy[1].

  • CAS Number: 481631-45-2
  • MF: C32H31N5O
  • MW: 501.62100
  • Catalog: PAI-1
  • Density: 1.21g/cm3
  • Boiling Point: 759.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 413ºC

Lys-Ala-pNA

Lys-Ala-pNA is hydrolytic substrate the of dipeptidyl peptidase (DPP) II with Km of 0.42 mM[1].

  • CAS Number: 115846-24-7
  • MF: C15H23N5O4
  • MW: 337.37
  • Catalog: Dipeptidyl Peptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Alirocumab

Alirocumab (REGN 727) is a human monoclonal antibody inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9). Alirocumab specifically binds PCSK9, a down regulator of liver low-density lipoprotein (LDL)-receptors, thereby increasing the ability of the liver to bind LDL-cholesterol (LDL-C) and reducing levels of LDL-C in blood. Alirocumab can be used for the research of hypercholesterolemia[1].

  • CAS Number: 1245916-14-6
  • MF: C6472H9996N1736O2032S42
  • MW:
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A