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.


Anti-infection >
Arenavirus Bacterial CMV Enterovirus Filovirus Fungal HBV HCV HIV HSV Influenza Virus Parasite Reverse Transcriptase RSV SARS-CoV
Antibody-drug Conjugate >
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Apoptosis >
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Antifolate APC ATM/ATR Aurora Kinase Casein Kinase CDK Checkpoint Kinase (Chk) CRISPR/Cas9 Deubiquitinase DNA Alkylator/Crosslinker DNA-PK DNA/RNA Synthesis Eukaryotic Initiation Factor (eIF) G-quadruplex Haspin Kinase HDAC HSP IRE1 Kinesin LIM Kinase (LIMK) Microtubule/Tubulin Mps1 Nucleoside Antimetabolite/Analog p97 PAK PARP PERK Polo-like Kinase (PLK) PPAR RAD51 ROCK Sirtuin SRPK Telomerase TOPK Topoisomerase Wee1
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Metabolic Enzyme/Protease >
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
Neuronal Signaling >
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Protein Tyrosine Kinase/RTK >
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KW-2478

KW-2478 is an inhibitor of Hsp90α, with an IC50 of 3.8 nM, and has antitumor activity against various human hematological tumor cells.

  • CAS Number: 819812-04-9
  • MF: C30H42N2O9
  • MW: 574.662
  • Catalog: HSP
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 746.9±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 405.5±32.9 °C

Methysticin

Methysticin is a major kavalactone in kava extract to induce CYP1A1.

  • CAS Number: 20697-20-5
  • MF: C15H14O5
  • MW: 274.269
  • Catalog: Cytochrome P450
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 496.5±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 223.9±28.8 °C

(S,S)-GSK321

(S,S)-GSK321 is a (S,S)-enantiomer of GSK321[1].

  • CAS Number: 1816272-20-4
  • MF: C28H28FN5O3
  • MW: 501.55
  • Catalog: Isocitrate Dehydrogenase (IDH)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CDD3505

CDD3505 is used for elevating high density lipoprotein cholesterol (HDL) by inducing hepatic cytochrome P450IIIA (CYP3A) activity.

  • CAS Number: 173865-33-3
  • MF: C22H17N3O2
  • MW: 355.389
  • Catalog: Cytochrome P450
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 515.7±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 265.7±28.7 °C

PF 356231

PF-00356231 hydrochloride is a specific, non-peptidic, non-zinc chelating ligand and inhibitor of matrix metalloproteinase MMP-12 (IC50=1.4 μM). PF-00356231 hydrochloride binds to MMP-12 and forms PF-00356231/MMP-12 complex. PF-00356231 hydrochloride shows potency against MMP-13, MMP-8, MMP-9, MMP-3 with IC50s of 0.00065, 1.7, 0.98, 0.39 μM, respectively[1].

  • CAS Number: 766536-21-4
  • MF: C25H20N2O3S
  • MW: 428.50
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Calpain-1 (pig)

Calpain-1 (pig) (μ-Calpain) is an intracellular Ca2+-regulated cysteine protease. Calpain-1 (pig) exhibits neuroprotective effect[1][2].

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

Nifurtimox

Nifurtimox, an antiprotozoal agent, which is generally used for the treatment of infections with Trypanosoma cruzi, has been used in the therapy of neuroblastoma. Nifurtimox affects enzyme activity of lactate dehydrogenase (LDH).

  • CAS Number: 23256-30-6
  • MF: C10H13N3O5S
  • MW: 287.29200
  • Catalog: Parasite
  • Density: 1.56g/cm3
  • Boiling Point: 550.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 286.6ºC

COX-2/15-LOX-IN-1

COX-2/15-LOX-IN-1 (Compound 14) is a COX-2 and 15-lipoxygenase enzyme (15-LOX) inhibitor with IC50 values of 10.65, 0.075 and 2.98 μM against COX-1, COX-2 and 15-LOX, respectively. COX-2/15-LOX-IN-1 shows anti-inflammatory activity[1].

  • CAS Number: 2413565-15-6
  • MF: C21H21N7S3
  • MW: 467.63
  • Catalog: COX
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TZ9

TZ9 is a novel inhibitor of Rad6 ubiquitin conjugating enzyme(E2 enzyme); inhibits MDA-MB-231 cell proliferation with IC50 of ~6 uM.IC50 value: 6 uM [1]Target: Rad6 inhibitorThe bulk of MDA-MB-231 cells treated with 10 μmol/L or more SMI #9 displayed a round morphology compared with controls and less than 5 μmol/L doses of SMI #9. Simultaneous comparison of SMIs #8 and 9 confirmed SMI #9 inhibits Matrigel-induced migration of MDA-MB-231 cells in a dose-dependent manner compared with SMI #8. 5 μmol/L SMI #9 treatment triggered morphologic changes consistent with apoptosis in a time-dependent manner. 5 μmol/L SMI #9 treatment of MDA-MB-231 cells for 24 hours increased the proportion of G2–M-arrested cells by 2-fold and was accompanied by a proportional decrease in S-phase cells. SMIs #8 or 9 treatments dramatically reduced β-catenin staining as visualized by reduced merged Rad6/β-catenin yellow fluorescence.

  • CAS Number: 1002789-86-7
  • MF: C17H14N6O4
  • MW: 366.331
  • Catalog: E1/E2/E3 Enzyme
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 675.9±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 362.6±34.3 °C

Isavuconazole D4

Isavuconazole D4 (BAL-4815 D4) is a deuterium labeled Isavuconazole (BAL-4815). Isavuconazole is a triazole prodrug with antifungal activity against yeasts, molds, and dimorphic fungi[1].

  • CAS Number: 1346598-58-0
  • MF: C22H13D4F2N5OS
  • MW: 441.490
  • Catalog: Fungal
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 678.0±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 363.8±34.3 °C

rilpivirine hydrochloride

Rilpivirine (R278474) hydrochloride is a potent and specific diarylpyrimidine (DAPY) non-nucleoside reverse transcriptase inhibitor (NNRTI). Rilpivirine hydrochloride has high antiviral activity against wild-type HIV (EC50=0.4 nM) and mutant viruses (EC50=0.1-2.0 nM). Rilpivirine hydrochloride has a high genetic barrier to resistance development of HIV[1][2].

  • CAS Number: 700361-47-3
  • MF: C22H19ClN6
  • MW: 402.88
  • Catalog: SARS-CoV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lonidamine

Lonidamine is an orally administered small molecule hexokinase inactivator.Target: OthersLonidamine is a derivative of indazole-3-carboxylic acid, which for a long time, has been known to inhibit aerobic glycolysis in cancer cells. It seems to enhance aerobic glycolysis in normal cells, but suppress glycolysis in cancer cells. This is most likely through the inhibition of the mitochondrially bound hexokinase. Later studies in Ehrlich ascites tumor cells showed that lonidamine inhibits both respiration and glycolysis leading to a decrease in cellular ATP. Clinical trials of lonidamine in combination with other anticancer agents for a variety of cancers has begun. Lonidamine has been used in the treatment of brain tumours in combination with radiotherapy and temozolomide. Results showed that a combination of temozolomide and lonidamine at clinically achievable, low plasma concentrations, could inhibit tumour growth, and lonidamine could reduce the dose of temozolomide required for radiosensitization of brain tumours. From Wikipedia.

  • CAS Number: 50264-69-2
  • MF: C15H10Cl2N2O2
  • MW: 321.158
  • Catalog: Hexokinase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 537.9±45.0 °C at 760 mmHg
  • Melting Point: 207-209°C
  • Flash Point: 279.1±28.7 °C

ITMN 4077

ITMN 4077 is a macrocyclic inhibitor against Hepatitis C Virus (HCV) NS3 protease (EC50: 2131 nM)[1][2].

  • CAS Number: 790305-05-4
  • MF: C26H40N4O8S
  • MW: 568.6828
  • Catalog: HCV Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BR351

BR351 is a brain penetrant MMP inhibitor with IC50s of 4, 2, 11, 50 nM for MMP2, MMP8, MMP9 and MMP13, respectively[1]. Potential tools for the molecular imaging of activated MMPs with PET[2].

  • CAS Number: 960113-85-3
  • MF: C20H25FN2O5S
  • MW: 424.49
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

nelumol a

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

  • CAS Number: 77836-86-3
  • MF: C21H30O4
  • MW: 346.46
  • Catalog: FXR
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 500.5±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 256.5±30.1 °C

6-Geranylnaringenin

Bonannione A (6-Geranylnaringenin; Mimulone), a prenylflavonoid, is an orally active and potent protein tyrosine phosphatase 1B (PTP1B) inhibitor with an IC50 of 14 µM. Bonannione A triggers caspase-dependent Apoptosis. Bonannione A induces Autophagy through p53-mediated AMPK/mTOR pathway. Bonannione A shows anti-inflammatory, antiradical and anti-cancer activity[1][2][3].

  • CAS Number: 97126-57-3
  • MF: C25H28O5
  • MW: 408.48682
  • Catalog: Apoptosis
  • Density: 1.219±0.06 g/cm3
  • Boiling Point: 647.8±55.0 °C at 760 mmHg
  • Melting Point: 116-118 °C
  • Flash Point: N/A

MitoTam iodide, hydriodide

MitoTam iodide, hydriodide is a tamoxifen derivative[1], an electron transport chain (ETC) inhibitor, spreduces mitochondrial membrane potential in senescent cells and affects mitochondrial morphology[2].MitoTam iodide, hydriodide is an effective anticancer agent, suppresses respiratory complexes (CI-respiration) and disrupts respiratory supercomplexes (SCs) formation in breast cancer cells[1][2]. MitoTam iodide, hydriodide causes apoptosis[2].

  • CAS Number: 1634624-74-0
  • MF: C52H60I2NOP
  • MW: 999.82
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

15,16-Dihydrotanshindiol C

15,16-Dihydrotanshindiol C, a diterpenoid, is a potent thrombin inhibitor[1][2].

  • CAS Number: 891854-96-9
  • MF: C18H18O5
  • MW: 314.332
  • Catalog: Thrombin
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 534.6±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 198.3±23.6 °C

Simvastatin acid

Simvastatin acid (Tenivastatin) is an orally active HMG-CoA reductase (HMGCR) inhibitor. Simvastatin acid can reduce cholesterol synthesis and lower blood cholesterol levels[1]. Simvastatin acid shows anti-proliferation activities against cancer cells and induces apoptosis[2].

  • CAS Number: 121009-77-6
  • MF: C25H40O6
  • MW: 436.58200
  • Catalog: Apoptosis
  • Density: 1.13g/cm3
  • Boiling Point: 607ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 198.2ºC

SCD inhibitor 1

SCD inhibitor 1 is a stearoyl-coa desaturase (SCD) extracted from patent WO/2009060053 A1, compound example 16.

  • CAS Number: 1150701-66-8
  • MF: C18H16Cl2N4O2
  • MW: 391.251
  • Catalog: Stearoyl-CoA Desaturase (SCD)
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Zaragozic acid B

Zaragozic acid B, a fungal metabolite, is a potent inhibitor of both farnesyl-protein transferase (FPTase) and squalene synthases. Zaragozic acid B is a potential anticancer drug[1].

  • CAS Number: 146389-61-9
  • MF: C39H54O13
  • MW: 730.83800
  • Catalog: Farnesyl Transferase
  • Density: 1.3g/cm3
  • Boiling Point: 871.6ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 260.4ºC

Palmitic acid-13C16 sodium

Palmitic acid-13C16 sodium is the 13C-labeled Palmitic acid sodium. Palmitic acid sodium is a long-chain saturated fatty acid commonly found in both animals and plants. Palmitic acid sodium can induce the expression of glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in in mouse granulosa cells[1][2].

  • CAS Number: 2483736-17-8
  • MF: 13C16H31NaO2
  • MW: 294.29
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ER21355

ER21355 is an inhibitor of phosphodiesterase 5 (PDE5), used for treatment of prostatic diseases.

  • CAS Number: 150452-18-9
  • MF: C22H21ClN4O4
  • MW: 440.88000
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Deoxyshikonin

Deoxyshikonin is isolated from Lithospermum erythrorhizon Sieb with antitumor activity. Deoxyshikonin increases the expression of VEGF-C and VEGF-A mRNA in HMVEC-dLy, promotes HIF-1α and HIF-1β subunit interaction and binds to specific DNA sequences targeted by HIF, indicates a prolymphangiogenesis as well as a proangiogenesis effect in vitro[1]. Deoxyshikonin shows significant synergic antimicrobial activity with tetracycline against S. pneumonia (MIC=17 μg/mL), also shows significantly inhibitory activities against MRSA[2].

  • CAS Number: 43043-74-9
  • MF: C16H16O4
  • MW: 272.296
  • Catalog: Bacterial
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 503.7±50.0 °C at 760 mmHg
  • Melting Point: 91ºC
  • Flash Point: 272.5±26.6 °C

hCAXII-IN-3

hCAXII-IN-3 (Compound 6o) is a selective human carbonic anhydrase XII (hCAXII) inhibitor with a Ki of 10.0 nM[1].

  • CAS Number: 2417232-24-5
  • MF: C26H20BrN5O3S
  • MW: 562.44
  • Catalog: Carbonic Anhydrase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bergaptol

BergaptolA hydroxylated psoralen that acts as a potent inhibitors of debenzylation activity of CYP3A4 enzyme with an IC50 value of 24.92 uM. Recent studies suggest that it may have antiproliferative and anticancer properties.target: CYP3A4 [1]IC50: 24.92 [1]For in vivo enzyme activity analysis, 100 μM bergaptol was added to the cultures for an additional 24 h at 37°C. After centrifugation, the supernatant was used to measure the bergapten yield by high performance liquid chromatography (HPLC).[2]

  • CAS Number: 486-60-2
  • MF: C11H6O4
  • MW: 202.163
  • Catalog: Cytochrome P450
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 311.9±11.0 °C at 760 mmHg
  • Melting Point: 287-290ºC
  • Flash Point: 142.4±19.3 °C

Hepatitis Virus C NS3 Protease Inhibitor 2

Hepatitis Virus C NS3 Protease Inhibitor 2 is a product-based peptide inhibitor of hepatitis C virus (HCV) NS3 protease, with a Ki of 41 nM[1].

  • CAS Number: 208939-95-1
  • MF: C43H56N6O14S
  • MW: 913.10
  • Catalog: HCV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Methyl Arachidonyl Fluorophosphonate

MAFP (Methyl Arachidonyl Fluorophosphonate) is an selective, active-site directed and irreversible inhibitor of cPLA2 and iPLA2. MAFP is also a potent irreversible inhibitor of anandamide amidase.

  • CAS Number: 188404-10-6
  • MF: C21H36FO2P
  • MW: 370.482
  • Catalog: Phospholipase
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 455.3±34.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 229.1±25.7 °C

XMD16-5

XMD16-5 is a potent TNK2 inhibitor with IC50 values of 16 and 77 nM for the D163E and R806Q mutations, respectively.

  • CAS Number: 1345098-78-3
  • MF: C23H24N6O2
  • MW: 416.476
  • Catalog: Tyrosinase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fexarine

Fexarine is a potent, non-steroidal and selective agonist of farnesoid X receptor (EC50: 38 nM). Fexarine can be used for the research of diseases linked to cholesterol, bile acids[1].

  • CAS Number: 574013-67-5
  • MF: C31H31NO5
  • MW: 497.58
  • Catalog: FXR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 681.2±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 365.8±31.5 °C