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 >
ADC Cytotoxin ADC Linker Drug-Linker Conjugates for ADC PROTAC-linker Conjugate for PAC
Apoptosis >
Apoptosis Bcl-2 Family c-Myc Caspase DAPK Ferroptosis IAP MDM-2/p53 PKD RIP kinase Survivin Thymidylate Synthase TNF Receptor
Autophagy >
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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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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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3-Hydroxy-3-(2H3)methylpentanedioic acid

Meglutol-d3 is the deuterium labeled Meglutol[1]. Meglutol is an antilipemic agent which lowers cholesterol, triglycerides, serum beta-lipoproteins and phospholipids, and inhibits the activity of hydroxymethylglutarryl CoA reductases, which is the rate limiting enzyme in the biosynthesis of cholesterol.

  • CAS Number: 59060-36-5
  • MF: C6H7D3O5
  • MW: 165.159
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 354.3±32.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 182.2±21.6 °C

A-908292

A-908292 is a highly potent and selective acetyl-CoA carboxylase 2 (ACC2) inhibitor with IC50 of 38 nM (hACC2), no activity against ACC1 (IC50>30 uM).

  • CAS Number: 903886-95-3
  • MF: C18H20N2O4S
  • MW: 360.428
  • Catalog: Acetyl-CoA Carboxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Milrinone

Milrinone is a PDE3 inhibitor, and also an inotrope and vasodilator.

  • CAS Number: 78415-72-2
  • MF: C12H9N3O
  • MW: 211.219
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 448.7±45.0 °C at 760 mmHg
  • Melting Point: >3000C
  • Flash Point: 225.2±28.7 °C

3-(2,4-Dihydroxyphenyl)propionic acid

3-(2,4-Dihydroxyphenyl)propanoic acid (DPPacid) is a potent and competitive tyrosinase inhibitor, inhibits L-Tyrosine and DL-DOPA with an IC50 and a Ki of 3.02 μM and 11.5 μM, respectively[1].

  • CAS Number: 5631-68-5
  • MF: C9H10O4
  • MW: 182.173
  • Catalog: Tyrosinase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 418.0±14.0 °C at 760 mmHg
  • Melting Point: 158-162ºC
  • Flash Point: 220.8±16.6 °C

SBP1 peptide

SBP1 peptide is a chemically synthesized 23-mer peptide fragment of the ACE2 PD α1 helix. SBP1 peptide associates with micromolar affinity to insect-derived SARS-CoV-2-RBD protein [1].

  • CAS Number: 2416761-69-6
  • MF: C127H184N30O42
  • MW: 2803.00
  • Catalog: SARS-CoV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

19 alpha-Hydroxyasiatic acid

19α-Hydroxyasiatic acid, a natural triterpenoid, possesses anti-elastase activity[1].

  • CAS Number: 70868-78-9
  • MF: C30H48O6
  • MW: 504.70
  • Catalog: Elastase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 283℃
  • Flash Point: N/A

Pitavastatin sodium

Pitavastatin (NK-104) sodium is a potent hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor. Pitavastatin sodium inhibits cholesterol synthesis from acetic acid with an IC50 of 5.8 nM in HepG2 cells. Pitavastatin sodium is an efficient hepatocyte low-density lipoprotein-cholesterol (LDL-C) receptor inducer. Pitavastatin sodium also possesses anti-atherosclerotic, anti-asthmatic, anti-osteoarthritis, antineoplastic, neuroprotective, hepatoprotective and reno-protective effects[1][2][3][8].

  • CAS Number: 574705-92-3
  • MF: C25H23FNNaO4
  • MW: 443.44300
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Z-Gly-Pro-Phe-Leu-CHO

Z-Gly-Pro-Phe-Leu-CHO (Z-GPFL-CHO) is a tetrapeptide aldehyde that acts as a highly selective and potent proteasomal inhibitor (Ki = 1.5 µM for branched chain amino acid preferring, 2.3 µM for small neutral amino acid preferring, and 40.5 µM for chymotrypsin-like activities; IC50 = 3.1 µM for peptidyl-glutamyl peptide hydrolyzing activity)[1].

  • CAS Number: 159659-05-9
  • MF: C30H38N4O6
  • MW: 550.65
  • Catalog: Proteasome
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MDL 101146

MDL 101146 is an orally active neutrophil elastase inhibitor. MDL 101146 inhibits neutrophil elastase for human with a Ki value of 25 nM. MDL 101146 can be used for the research of arthritis[1][2].

  • CAS Number: 149859-17-6
  • MF: C29H37F5N4O6
  • MW: 632.61900
  • Catalog: Elastase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sophora-iso-flavone A

Sophoraisoflavone A (Allolicoisoflavone B) is a nature product that could be isolated from Glycyrrhiza inflate. Sophoraisoflavone A is a potent protein tyrosine phosphatase 1B (PTP1B) inhibitor with an IC50 value of 0.80 μM. Sophoraisoflavone A can be used in research of inflammation[1].

  • CAS Number: 117204-81-6
  • MF: C20H16O6
  • MW: 352.34
  • Catalog: Phosphatase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 611.2±55.0 °C at 760 mmHg
  • Melting Point: 235-237℃
  • Flash Point: 223.9±25.0 °C

Skp2 inhibitor 2

Skp2 inhibitor 2 (14f) is an inhibitor of F-box protein S-phase kinase-associated protein 2 (Skp2), with an IC50 value of 10.2 μM (Skp2-Cks1). Skp2 is a part of cullin-RING ligases, which recruits and ubiquitinates substrates, involving in proteolytic and non-proteolytic process[1].

  • CAS Number: 2760612-77-7
  • MF: C27H32N4O
  • MW: 428.57
  • Catalog: E1/E2/E3 Enzyme
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Perindopril

Perindopril is a long-acting ACE inhibitor of which is used to treat high blood pressure, heart failure or stable coronary artery disease.Target: ACEPerindopril is a long-acting ACE inhibitor. It is used to treat high blood pressure, heart failure or stable coronary artery disease in form of perindopril arginine (trade names include Coversyl, Coversum) or perindopril erbumine (trade name Aceon). According to the Australian government's Pharmaceutical Benefits Scheme website, based on data provided to the Australian Department of Health and Aging by the manufacturer, perindopril arginine and perindopril erbumine are therapeutically equivalent and may be interchanged without differences in clinical effect. However the dose prescribed to achieve the same effect will differ due to different molecular weights for the two forms. Perindopril is one of the most prescribed inhibitors of angiotensin converting enzyme, has a large evidence base, which allows to use it in patients with hypertension, diabetes mellitus type 2, coronary heart disease and chronic heart failure. In this review, the author focused on the evidence of organoprotecting properties of perindopril that lie outside lowering blood pressure.

  • CAS Number: 82834-16-0
  • MF: C19H32N2O5
  • MW: 368.468
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 537.4±45.0 °C at 760 mmHg
  • Melting Point: 100-101°C
  • Flash Point: 278.8±28.7 °C

Microcystin RR

Microcystin-RR (Cyanoviridin RR) is a potent and orally active protein phosphatase inhibitor. Microcystin-RR induces Apoptosis and ER stress in mice liver[1][2].

  • CAS Number: 111755-37-4
  • MF: C49H75N13O12
  • MW: 1038.200
  • Catalog: Apoptosis
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: 11 °C

PF-06424439

PF-06424439 is an oral, potent and selective imidazopyridine diacylglycerol acyltransferase 2 (DGAT2) inhibitor with an IC50 of 14 nM[1]. PF-06424439 is slowly reversible, time-dependent inhibitor, which inhibits DGAT2 in a noncompetitive mode with respect to the acyl-CoA substrate[2].

  • CAS Number: 1469284-78-3
  • MF: C22H26ClN7O
  • MW: 439.94
  • Catalog: Acyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TD-0212 TFA

TD-0212 TFA is an orally active dual pharmacology angiotensin II type 1 receptor (AT1) antagonist and neprilysin (NEP) inhibitor, with a pKi of 8.9 for AT1 and a pIC50 of 9.2 for NEP[1].

  • CAS Number: 1073549-11-7
  • MF: C30H35F4N3O6S
  • MW: 641.67
  • Catalog: Angiotensin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK837149A

GSK837149A is a selective inhibitor of human Fatty Acid Synthase (FASN) targeting the KR domain. GSK837149A has reversible inhibition effect on FASN and selectivity for type I FASN (Ki=30 nM). GSK837149A is also a competitive inhibitor of NADPH and a non-competitive inhibitor of acetoacetyl-CoA. GSK837149A can be used for the research of obesity and breast cancer[1][2].

  • CAS Number: 13616-29-0
  • MF: C23H22N8O5S2
  • MW: 554.60100
  • Catalog: Fatty Acid Synthase (FAS)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LXRβ agonist-3

LXRβ agonist-3 (compound 4-13) is a potent and selective LXRβ (liver X receptor β) agonist, with an EC50 of 0.095 μM. LXRβ agonist-3 efficiently inhibits U87EGFRvIII cell, with an IC50 of 3.75 μM. LXRβ agonist-3 shows antitumor activity, and can inhibit glioblastoma[1].

  • CAS Number: 2413308-63-9
  • MF: C30H33N3O6S
  • MW: 563.66
  • Catalog: LXR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NEP-IN-2

NEP-IN-2 is an inhibitor of neutral endopeptidase, used in the research of proliferation in atherosclerosis, restenosis.

  • CAS Number: 145775-14-0
  • MF: C16H23NO3S2
  • MW: 341.48900
  • Catalog: Neprilysin
  • Density: 1.204g/cm3
  • Boiling Point: 603ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 318.5ºC

L-690,330

L-690330 is a competitive inhibitor of inositol monophosphatase (IMPase) with a Kis of 0.27 and 0.19 μM for recombinant human and bovine IMPase, 0.30 and 0.42 μM for human and bovine frontal cortex IMPase, respectively, exhibits 10-fold more sensitive than mouse and rat IMPase[1].

  • CAS Number: 142523-38-4
  • MF: C8H12O8P2
  • MW: 298.12400
  • Catalog: Phosphatase
  • Density: 1.787g/cm3
  • Boiling Point: 696.9ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 375.3ºC

Tamibarotene

Tamibarotene is a retinoic acid receptor α/β (RARα/β) agonist, showing high selectivity over RARγ.

  • CAS Number: 94497-51-5
  • MF: C22H25NO3
  • MW: 351.439
  • Catalog: RAR/RXR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 449.6±45.0 °C at 760 mmHg
  • Melting Point: 231-232ºC
  • Flash Point: 225.7±28.7 °C

BAY-678 racemate

BAY-678 racemate is a racemate of BAY-678. BAY-678 is an orally bioavailable, highly potent, selective and cell-permeable inhibitor of human neutrophil elastase (HNE), with an IC50 of 20 nM. BAY-678 is also nominated as a chemical probe to the public via the Structural Genomics Consortium (SGC).

  • CAS Number: 675103-35-2
  • MF: C20H15F3N4O2
  • MW: 400.35
  • Catalog: Elastase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

U27391

U27391 is a metalloproteinase inhibitor. U27391 inhibits rhIL-1β Induced proteoglycan loss[1].

  • CAS Number: 106314-87-8
  • MF: C23H36N4O5
  • MW: 448.55600
  • Catalog: MMP
  • Density: 1.156g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lorundrostat

Lorundrostat is a aldosterone synthase inhibitor[1].

  • CAS Number: 1820940-17-7
  • MF: C24H33N7O2
  • MW: 451.56
  • Catalog: Mineralocorticoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Flavokawain 1i

Flavokawain 1i (DiNap) is an Hsp90 inhibitor. Flavokawain 1i (DiNap) has anti-cell proliferation activity and can be used in cancer research[1].

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

Lonafarnib

Lonafarnib is an orally bioavailable farnesyl protein transferase (FPTase) inhibitor for H-ras, K-ras and N-ras with IC50 of 1.9 nM, 5.2 nM and 2.8 nM, respectively.

  • CAS Number: 193275-84-2
  • MF: C27H31Br2ClN4O2
  • MW: 638.822
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 710.4±70.0 °C at 760 mmHg
  • Melting Point: 214.5-215.9° (monohydrate); mp 222-223°
  • Flash Point: 383.5±35.7 °C

Isosilybin

Isosilybin (Isosilybinin) is a flavonoid from milk thistle; inhibits CYP3A4 induction with an IC50 of 74 μM.

  • CAS Number: 72581-71-6
  • MF: C25H22O10
  • MW: 482.436
  • Catalog: Cytochrome P450
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 793.0±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 274.5±26.4 °C

Nefazodone

Nefazodone is an orally active phenylpiperazine antidepressant. Nefazodone can potently and selectively block postsynaptic 5-HT2A receptors, and moderately inhibit 5-HT and noradrenaline reuptake. Nefazodone can also relieve the adverse effects of stress on the the immune system of mice. Nefazodone has a high affinity for CYP3A4 isoenzyme, which indicates that it has certain risk of drug-drug interaction[1][2][3].

  • CAS Number: 83366-66-9
  • MF: C25H32ClN5O2
  • MW: 470.00700
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 180-182°C
  • Flash Point: N/A

Rosiptor

Rosiptor is an activator of SH2-containing inositol-5'-phosphatase 1 (SHIP1).

  • CAS Number: 782487-28-9
  • MF: C20H35NO2
  • MW: 321.497
  • Catalog: Phosphatase
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 451.6±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 226.9±28.7 °C

Avanafil

Avanafil(TA-1790) is a potent and highly selective phosphodiesterase-5(PDE-5) inhibitor(IC50=5.2 nM) for erectile dysfunction; lower selectivity against PDE1, PDE6, and PDE11.IC50 value: 5.2 nM [1]Target: PDE5Avanafil is highly selective toward PDE5 and against all other PDE isozymes tested. Lower selectivity against PDE1, PDE6, and PDE11 is consistent with results from randomized, placebo-controlled, phase 3 trials in which musculoskeletal and hemodynamic adverse events were reported in <2% of patients and no color vision-related abnormalities were reported with avanafil doses up to 200mg once daily [2]. Intraduodenal doses of avanafil or sildenafil (0.1 and 1 mg/kg) potentiated the AUC of nitroglycerin induced hypotension. However, the potentiating effect of avanafil at 1 mg/kg was significantly weaker than that of sildenafil (p <0.05) [3].

  • CAS Number: 330784-47-9
  • MF: C23H26ClN7O3
  • MW: 483.951
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 150-152ºC
  • Flash Point: N/A

MMPI-1154

MMPI-1154 is a small molecule MMP-2 inhibitor with IC50 of 10/6.6/13/1.8 uM for MMP1/2/9/13, respectively; shows significant cardio-cytoprotecion, significantly decreases infarct size when applied at 1 μM in an ex vivo model for acute myocardial infarction.

  • CAS Number: 1382722-47-5
  • MF: C26H24FN3O3
  • MW: 445.494
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A