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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ERK JNK KLF MAP3K MAP4K MAPKAPK2 (MK2) MEK Mixed Lineage Kinase MNK p38 MAPK Raf Ribosomal S6 Kinase (RSK)
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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
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Clarithromycin

Clarithromycin is a macrolide antibiotic and a CYP3A4 inhibitor.Target: Antibacterial; CYP3A4Clarithromycin is a macrolide antibiotic used to treat pharyngitis, tonsillitis, acute maxillary sinusitis, acute bacterial exacerbation of chronic bronchitis, pneumonia (especially atypical pneumonias associated with Chlamydophila pneumoniae), skin and skin structure infections. Clarithromycin prevents bacteria from growing by interfering with their protein synthesis. It binds to the subunit 50S of the bacterial ribosome and thus inhibits the translation of peptides. Clarithromycin has similar antimicrobial spectrum as erythromycin, but is more effective against certain Gram-negative bacteria, particularly Legionella pneumophila. Besides this bacteriostatic effect, clarithromycin also has bactericidal effect on certain strains, such as Haemophilus influenzae, Streptococcus pneumoniae and Neisseria gonorrhoeae. Clarithromycin is a CYP3A4 inhibitor. Even low doses of the cytochrome P4503A4 (CYP3A4) inhibitor clarithromycin increase the plasma concentrations and effects of repaglinide. Concomitant use of clarithromycin or other potent inhibitors of CYP3A4 with repaglinide may enhance its blood glucose-lowering effect and increase the risk of hypoglycemia [1, 2].

  • CAS Number: 81103-11-9
  • MF: C38H69NO13
  • MW: 747.953
  • Catalog: Bacterial
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 805.5±65.0 °C at 760 mmHg
  • Melting Point: 217-220ºC
  • Flash Point: 440.9±34.3 °C

SQ 28853

SQ 28853 is an inhibitor of ACE with diuretic properties.

  • CAS Number: 107550-68-5
  • MF: C19H25ClN4NaO6S3
  • MW: 560.05
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Edoxaban tosylate monohydrate

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: 1229194-11-9
  • MF: C31H40ClN7O8S2
  • MW: 738.274
  • Catalog: Factor Xa
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Enalaprilat Dihydrate

Enalaprilat is an angiotensin-converting enzyme (ACE) inhibitor with IC50 of 1.94 nM.Target: ACEEnalaprilat has high affinity for human endothelial ACE with IC50 of 1.94 nM in vitro binding assay by displacing a saturating concentration of [125I]351A, a radiolabeled lisinopril analogue from ACE binding sites, and shows bradykinin/angiotensin I selectivity ratio of 1.00 calculated from double displacement experiments [1]. Enalaprilat attenuates the IGF-I induced neonatal rat cardiac fibroblast growth (30% reduction) in a concentration-dependent fashion, with IC50 of 90 mM [2].Administration of Enalaprilat induces a significant reduction of MAP at 70 minutes compared with the placebo group during haemorrhagic shock in rats, and results in a 50% reduction of CO, a general tendency of EB extravasation which is significant in the kidney and lungs, and a significant increase in ileal EB extravasation (53%) [3].

  • CAS Number: 84680-54-6
  • MF: C18H28N2O7
  • MW: 384.424
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: 563.5ºC at 760 mmHg
  • Melting Point: 211-215°C
  • Flash Point: 294.6ºC

SSR 69071

SSR69071 is a potent, orally active and selective inhibitor of neutrophil elastase. SSR69071 reduces myocardial infarct size following ischemia-reperfusion injury[1]. SSR69071 displays a higher affinity for human elastase (Ki=0.0168 nM) than for rat (Ki=3 nM), mouse (Ki=1.8 nM), and rabbit (Ki= 58 nM) elastases[2].

  • CAS Number: 344930-95-6
  • MF: C27H32N4O7S
  • MW: 556.63100
  • Catalog: Elastase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MUN57694

MUN57694 is 26S proteasome inhibitor. MUN57694 was reported in WO 2006128196. This product has not formal name. For the convenience of scientific communication, we named it by combining its Inchi key (3 letters from the first letter of each section) with the last 5 digits of its CAS number or its molecule weight if its CAS number is not available 

  • CAS Number: 858557-69-4
  • MF: C23H25N3O4
  • MW: 407.46
  • Catalog: Proteasome
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fotagliptin Benzoate

Fotagliptin benzoate is a Dipeptidyl Peptidase IV (DPP-4) inhibitor (IC50=2.27 nM). Fotagliptin benzoate displays great security in rat and dog. Fotagliptin benzoate can be used for Type 2 diabetes mellitus research[1].

  • CAS Number: 1403496-40-1
  • MF: C24H25FN6O3
  • MW: 464.49
  • Catalog: Dipeptidyl Peptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

D,L-erythro-Dihydrosphingosine

DL-erythro-Dihydrosphingosine is a potent inhibitor of PKC and phospholipase A2 (PLA2)[1][2].

  • CAS Number: 3102-56-5
  • MF: C18H39NO2
  • MW: 301.50800
  • Catalog: PKC
  • Density: 0.927g/cm3
  • Boiling Point: 446.2ºC at 760 mmHg
  • Melting Point: 70-72ºC
  • Flash Point: 223.7ºC

7-Methoxy obtusifolin

7-Methoxy obtusifolin (Compound 4) is a competitive tyrosinase inhibitor with an IC50 of 7.0 μM[1].

  • CAS Number: 1820806-09-4
  • MF: C17H14O6
  • MW: 314.29
  • Catalog: Tyrosinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ulinastatin

Ulinastatin (Uristatin) is a trypsin and serine protease inhibitor. Ulinastatin is the main protein binding inhibitor of various trypsin, chymotrypsin, and various pancreatic proteases. Ulinastatin shows neuroprotective, anti-inflammatory, anti-apoptotic, anti-oxidant effects[1][2].

  • CAS Number: 80449-31-6
  • MF: C13H16O3
  • MW: 220.264
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 331.5±42.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 171.0±16.8 °C

Compound 48/80 (hydrochloride)

Compound 48/80 trihydrochloride (C48/80 trihydrochloride) is a mixture of condensation products of N-methyl-p-methoxyphenethylamine with formaldehyde. Compound 48/80 trihydrochloride is also a histamine releaser and a mast cell degranulator. Compound 48/80 inhibits phosphatidylinositol-specific phospholipase C activity from human platelets [1][2][3].

  • CAS Number: 848035-21-2
  • MF: C32H48Cl3N3O3
  • MW: 629.10
  • Catalog: Phospholipase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ONO-3307

ONO-3307 is a protease inhibitor that competitively inhibits a variety of proteases including trypsin, thrombin, plasma kallikrein, plasmin, pancreatic kallikrein, and chymotrypsin. ONO-3307 alleviates endotoxin-induced experimental disseminated intravascular coagulation (DIC) in rats. ONO-3307 can be used in the study of thrombosis and protease-mediated diseases[1][2].

  • CAS Number: 76472-29-2
  • MF: C15H18N4O7S2
  • MW: 430.45600
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Atorvastatin

Atorvastatin is an inhibitor of HMG-CoA reductase used as a cholesterol-lowering medication that blocks the production of cholesterol. Target: HMG-CoA reductaseAtorvastatin is an inhibitor of HMG-CoA reductase used as a cholesterol-lowering medication that blocks the production of cholesterol. 81 patients were randomly assigned to receive either placebo or 2.5, 5, 10, 20, 40, or 80 mg atorvastatin once daily for 6 weeks. Plasma LDL cholesterol reductions from baseline were dose related, with 25% to 61% reduction from the minimum dose to the maximum dose of 80 mg atorvastatin once a day [1]. Atorvastatin 10 mg daily is safe and efficacious in reducing the risk of first cardiovascular disease events, including stroke, in patients with type 2 diabetes without high LDL-cholesterol. No justification is available for having a particular threshold level of LDL-cholesterol as the sole arbiter of which patients with type 2 diabetes should receive statins [2].

  • CAS Number: 134523-00-5
  • MF: C33H35FN2O5
  • MW: 558.64
  • Catalog: HMG-CoA Reductase (HMGCR)
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 722.2±60.0 °C at 760 mmHg
  • Melting Point: 176-178°C
  • Flash Point: 390.6±32.9 °C

Senazodan

Senazodan is a Ca2+ sensitiser, and also shows inhibition effect on PDE III.

  • CAS Number: 98326-32-0
  • MF: C15H14N4O
  • MW: 266.29800
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.3g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

T0901317

T0901317 is a potent and selective agonist for LXR and FXR, with EC50s of 50 nM and 5 μM, respectively.

  • CAS Number: 293754-55-9
  • MF: C17H12F9NO3S
  • MW: 481.333
  • Catalog: FXR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 470.5±55.0 °C at 760 mmHg
  • Melting Point: 116-122° C
  • Flash Point: 238.4±31.5 °C

Simvastatin-d3

Simvastatin-d3 is the deuterium labeled Simvastatin[1]. Simvastatin (MK 733) is a competitive inhibitor of HMG-CoA reductase with a Ki of 0.2 nM[2].

  • CAS Number: 1002347-61-6
  • MF: C25H35D3O5
  • MW: 421.58500
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sacubitril/valsartan (LCZ696)

LCZ696 is a dual angiotensin II receptor and neprilysin inhibitor.

  • CAS Number: 936623-90-4
  • MF: C48H60N6Na3O10.5
  • MW: 957.99
  • Catalog: Angiotensin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ticlopidine

Ticlopidine (PCR 5332), an antithrombotic prodrug, acts as an allosteric, noncompetitive inhibitor of CD39 with the IC50 of 81.7 µM. Ticlopidine blocks several NTPDase isoenzymes with IC50s of 170 µM and 149 µM for NTPDase2 and NTPDase3, respectively[1]. Ticlopidine is an inhibitor of CYP2C19 human liver cytochrome. Ticlopidine inhibits CYP2C9 and CYP3A4 with IC50s of 26.0 and 32.3 μM, respectively[2][3].

  • CAS Number: 55142-85-3
  • MF: C14H14ClNS
  • MW: 263.786
  • Catalog: Cytochrome P450
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 367.3±37.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 175.9±26.5 °C

IDO antagonist-1

IDO antagonist-1 (compound 163) is an antagonist of IDO . IDO antagonist-1 inhibits pancreatic adenocarcinoma cells growth in C57BL/6 mice[1].

  • CAS Number: 2206797-88-6
  • MF: C39H53N7O5
  • MW: 699.88
  • Catalog: Indoleamine 2,3-Dioxygenase (IDO)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

M1002

M1002 is a hypoxia-inducible factor-2 (HIF-2) agonist, and can enhance the expression of HIF-2 target genes. M1002 shows synergy with prolyl-hydroxylase domain (PHD) inhibitors[1].

  • CAS Number: 823830-85-9
  • MF: C15H8F6N2O2S
  • MW: 394.292
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 414.6±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 204.6±31.5 °C

Naphthofluorescein

Naphthofluorescein inhibits the interaction between HIF-1 and Mint3.Naphthofluorescein suppresses Mint3-dependent HIF-1 activity and glycolysis in cancer cells and macrophages without cytotoxicity in vitro and adverse effect in vivo[1]. Naphthofluorescein is also a fluorescent pH-sensitive probe that can be used for functional Cerenkov imaging[2].

  • CAS Number: 61419-02-1
  • MF: C28H16O5
  • MW: 432.424
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 755.5±60.0 °C at 760 mmHg
  • Melting Point: 189ºC (dec.)(lit.)
  • Flash Point: 266.4±26.4 °C

ZM223

ZM223 is a novel non-sulfamide NEDD8 activating enzyme inhibitor that inhibits HCT116 colon cancer cells with an IC50 value of 100 nM.

  • CAS Number: 2031177-48-5
  • MF: C23H17F3N4O2S2
  • MW: 502.53
  • Catalog: NEDD8-activating Enzyme
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IPI-504

Retaspimycin Hydrochloride is a potent and water-soluble inhibitor of Hsp90 with EC50s of 119 nM for both Hsp90 and Grp9.

  • CAS Number: 857402-63-2
  • MF: C31H46ClN3O8
  • MW: 624.17
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TPN729MA

TPN729MA (TPN729 maleate) is a selective phosphodiesterase type 5 (PDE5) inhibitor with an IC50 value of 2.28 nM. TPN729MA affects erectile function and it can be used for the research of erectile dysfunction[1].

  • CAS Number: 1422955-52-9
  • MF: C29H40N6O8S
  • MW: 632.73
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tutuilamide A

Tutuilamide A is a potent porcine pancreatic elastase (PPE) inhibitor, with an IC50 of 1.2 nM. Tutuilamide A also inhibits human neutrophil elastase (HNE; IC50=0.73 nM) and kallikrein 7 (KLK7; IC50=5.0 nM)[1].

  • CAS Number: 2756129-42-5
  • MF: C51H69ClN8O12
  • MW: 1021.59
  • Catalog: Elastase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Oglemilast

Oglemilast(GRC3886) is a potent PDE4 inhibitor, under clinical studies in the treatment of allergen-induced asthma.IC50 value:Target: PDE4

  • CAS Number: 778576-62-8
  • MF: C20H13Cl2F2N3O5S
  • MW: 516.30
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 287.8±40.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 136.5±20.6 °C

L-Ascorbic Acid 2-phosphate (magnesium salt hydrate)

L-ascorbic acid 2-phosphate (2-Phospho-L-ascorbic acid) magnesium hydrate is a long-acting vitamin C derivative that can stimulate collagen formation and expression. L-ascorbic acid 2-phosphate magnesium hydrate can be used as a culture medium supplement for the osteogenic differentiation of human adipose stem cells (hASCs). L-ascorbic acid 2-phosphate magnesium hydrate increases alkaline phosphatase (ALP) activity and expression of runx2A in hASCs during the osteogenic differentiation[1][2][3].

  • CAS Number: 1713265-25-8
  • MF: C12H12Mg3O18P2·xH2O
  • MW:
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PDE1-IN-2

PDE1-IN-2 is an inhibitor of PDE1 extracted from patent WO2016/55618 A1, example 31; has IC50 values of 6, 140 and 164 nM for PDE1C, PDE1B and PDE1A, respectvely.

  • CAS Number: 1904611-63-7
  • MF: C16H21BrN4O2
  • MW: 381.267
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 563.8±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 294.8±32.9 °C

Trimegestone

Trimegestone (RU 27987) is an orally active 19-norpregnane progestin. Trimegestone binds to progesterone receptor (PR) with an IC50 value of 3.3 nM (rat PR). Trimegestone increases alkaline phosphatase activity (EC50=0.1 nM) but not luciferase activity. Trimegestone also shows a weak antiandrogenic activity (weak androgen receptor affinity). Trimegestone can be used in studies of contraception or menopausal syndromes[1][2].

  • CAS Number: 74513-62-5
  • MF: C22H30O3
  • MW: 342.47
  • Catalog: Phosphatase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 522.6±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 284.0±26.6 °C

Fondaparinux Sodium

Fondaparinux sodium is an antithrombin-dependent factor Xa inhibitor.

  • CAS Number: 114870-03-0
  • MF: C31H53N3Na10O49S8
  • MW: 1738.16
  • Catalog: Factor Xa
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A