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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DABCYL-γ-Abu-Pro-Gln-Gly-Leu-Glu(EDANS)-Ala-Lys-NH2

TNO211 is a biological active peptide. (Matrix Metalloproteinases (MMPs) are a large family of endopeptidases. Collectively, MMPs can degrade all kinds of extracellular matrix proteins, and can also process a number of bioactive molecules. They are known to be involved in the cleavage of cell surface receptors, the release of apoptotic ligands, and chemokine/cytokine inactivation. MMPs are also thought to play a major role in cell behaviors such as cell proliferation, migration (adhesion/dispersion), differentiation, angiogenesis, apoptosis, and host defense.This peptide is a highly soluble fluorogenic MMP substrate for MMP-2, 8, 12, 13 and 14, containing the MMP cleavable Gly-Leu bond and EDANS/DABCYL. Fluorogenic assays using TNO211 are sensitive and can detect MMP activity in culture medium from endothelial cells and untreated synovial fluid from patients. Abs/Em = 340/490 nm.)

  • CAS Number: 193475-71-7
  • MF: C63H88N16O14S
  • MW: 1325.54
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ac-Glu-Asp(EDANS)-Lys-Pro-Ile-Leu-Phe-Phe-Arg-Leu-Gly-Lys(DABCYL)-Glu-NH2 trifluoroacetate salt

Ac-Glu-Asp(EDANS)-Lys-Pro-Ile-Leu-Phe-Phe-Arg-Leu-Gly-Lys(DABCYL)-Glu-NH2 is a cathepsin D substrate, that can be used for cathepsin D FRET assay[1].

  • CAS Number: 400716-78-1
  • MF: C104H146N24O23S
  • MW: 2132.484
  • Catalog: Cathepsin
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Palmatine hydroxide

Palmatine hydroxide is an orally active and irreversible indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor with IC50s of 3 μM and 157μM against HEK 293-hIDO-1 and rhIDO-1, respectively. Palmatine hydroxide can also inhibit West Nile virus (WNV) NS2B-NS3 protease in an uncompetitive manner with an IC50 of 96 μM. Palmatine hydroxide shows anti-cancer, anti-oxidation, anti-inflammatory, neuroprotection, antibacterial, anti-viral activities[1][2][3][4][5].

  • CAS Number: 131-04-4
  • MF: C21H23NO5
  • MW: 369.41100
  • Catalog: Bacterial
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cathepsin D and E FRET Substrate

Cathepsin D and E FRET Substrate is a fluorogenic substrate for cathepsins D and E and not for B, H or L. The cleavage occurs at the Phe-Phe amide bond resul. Cathepsin D and E FRET Substrate is a valuable tool for routine assays and for mechanistic studies on cathepsins E and D[1].

  • CAS Number: 839730-93-7
  • MF: C85H122N22O19
  • MW: 1756.014
  • Catalog: Cathepsin
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IDO1/TDO-IN-6

IDO1/TDO-IN-6 (compound 11) is a dual inhibitor of IDO1/TDO with IC50s of 2.25 and 2.89 μM, respectively. IDO1/TDO-IN-6 has inhibitory effects on IDO1 and TDO, with Ki values of 1.9 and 3.1 μM, respectively. IDO1/TDO-IN-6 can be used in cancer and immunology research[1].

  • CAS Number: 2948772-71-0
  • MF: C20H17NO5
  • MW: 351.35
  • Catalog: Indoleamine 2,3-Dioxygenase (IDO)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JG-98

JG-98 is an allosteric heat shock protein 70 (Hsp70) inhibitor with anti-cancer activities, which disrupts Hsp70 interaction with a co-chaperone Bag3 and affects signaling pathways important for cancer development[1][2][3].

  • CAS Number: 1456551-16-8
  • MF: C24H21Cl2N3OS3
  • MW: 534.54
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GNE-617

GNE-617 is a specific NAMPT inhibitor that inhibits the biochemical activity of NAMPT with an IC50 of 5 nM and exhibits efficacy in xenograft models of cancer.

  • CAS Number: 1362154-70-8
  • MF: C21H15F2N3O3S
  • MW: 427.42400
  • Catalog: Nampt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

OHM1

OHM1 is a potent HIF1α mimic that binds to CH1 domain of p300/CBP with Kd of 500 nM, reduces the level of HIF1α transcriptional activity under hypoxia to that observed under normoxia at 20 uM in A549 cells; reduces the median tumor volume in murine tumor xenografts, and does not cause measurable changes in animal body weight or other signs of toxicity in tumor-bearing animals.

  • CAS Number: 1450995-09-1
  • MF: C24H42N6O5
  • MW: 494.637
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2',2'-Dimethyl-2H,2'H-3,8'-bichromene-5',7-diol

Glabrene, an isoflavene derived from licorice root, shows estrogen-like activity. Glabrene is a tyrosinase inhibitor with an IC50 of 3.5 μM[1][2].

  • CAS Number: 60008-03-9
  • MF: C20H18O4
  • MW: 322.354
  • Catalog: Tyrosinase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 536.3±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 278.2±30.1 °C

JZL184

JZL 184 is a potent and selective inhibitor of MAGL with IC50 of 8 nM and 4 μM for inhibition of MAGL and FAAH in mouse brain membranes respectively.IC50 value: 8 nM [1]Target: MAGL inhibitorin vitro: JZL184 prolongs DSE in Purkinje neurons in cerebellar slices and DSI in CA1 pyramidal neurons in hippocampal slices. JZL184 is more potent in inhibiting mouse MAGL than rat MAGL [2]. in vivo: When administered to mice at 16 mg/kg, intraperitoneally, JZL 184 reduces MAGL activity by 85%, elevates brain 2-AG levels by 8-fold, and elicits analgesic activity in a variety of pain assays that qualitatively mimics direct central cannabinoid (CB1) agonists [1]. Acute administration of JZL184 to FAAH(-/-) mice enhanced the magnitude of a subset of cannabimimetic responses, repeated JZL184 treatment led to tolerance to its antinociceptive effects, cross-tolerance to the pharmacological effects of Δ(9)-tetrahydrocannabinol, decreases in CB1 receptor agonist-stimulated guanosine 5'-O-(3-[(35)S]thio)triphosphate binding, and dependence as indicated by rimonabant-precipitated withdrawal behaviors, regardless of genotype [3].

  • CAS Number: 1101854-58-3
  • MF: C27H24N2O9
  • MW: 520.487
  • Catalog: MAGL
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 706.4±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 381.0±32.9 °C

Dolutegravir (GSK1349572)

Dolutegravir is a second-generation HIV integrase strand transfer inhibitor (INSTI) with an IC50 of 2.7 nM.

  • CAS Number: 1051375-16-6
  • MF: C20H19F2N3O5
  • MW: 419.379
  • Catalog: HIV
  • Density: 1.53 g/cm3
  • Boiling Point: 669.0±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 358.4±31.5 °C

Melittin (free acid) trifluoroacetate salt

Melittin free acid is a basic 26-amino-acid polypeptide, the major active ingredient of honeybee venom. Melittin free acid is an activator of phospholipase A2 (PLA2). Melittin free acid has broad-spectrum antifungal activity with MIC values of 0.4-60 μM. Melittin free acid hinders fungal growth by inducing cell apoptosis, repressing (1,3)-β-D-glucan synthase and participating in other pathways[1][2].

  • CAS Number: 123168-46-7
  • MF: C131H228N38O32
  • MW: 2847.448
  • Catalog: Fungal
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Imidapril (hydrochloride)

Imidapril Hydrochloride is the hydrochloride salt of Imidapril, an angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Target: ACEAs a prodrug, Imidapril is converted by hydrolysis in the liver into its active form imidaprilat. Imidaprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Imidaprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.

  • CAS Number: 89396-94-1
  • MF: C20H28ClN3O6
  • MW: 441.91
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: N/A
  • Boiling Point: 577ºC at 760 mmHg
  • Melting Point: 38-42ºC
  • Flash Point: N/A

Enpp-1-IN-4

Enpp-1-IN-4 is a potent inhibitor of ectonucleotide pyrophosphatase-phosphodiesterase 1 (enpp-1). Enpp-1-IN-4 has the potential for the research of cancer diseases (extracted from patent WO2019177971A1, compound 1)[1].

  • CAS Number: 2376600-89-2
  • MF: C19H19N5O5S
  • MW: 429.45
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

hCAXII-IN-1

These compounds show selective inhibition on tumor related subtypes HCA IX and XII, and are also considered as the leading molecules for the development of future cancer therapeutic drugs based on new mechanisms of action.

  • CAS Number: 2451479-66-4
  • MF: C20H17NO5
  • MW: 351.35
  • Catalog: Carbonic Anhydrase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ARM-1

ARM1 (4BSA) is a potent aminopeptidase and epoxide hydrolase inhibitor. ARM1 shows aminopeptidase inhibitory activity with an IC50 7.61 µM and epoxide hydrolase inhibitory activity with an IC50 12.4 µM[1].

  • CAS Number: 68729-05-5
  • MF: C16H14N2S
  • MW: 266.361
  • Catalog: Aminopeptidase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 462.7±24.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 233.6±22.9 °C

Dehydrotrametenolic acid

3-​Dehydrotrametenolic acid, isolated from the sclerotium of Poria cocos, is a lactate dehydrogenase (LDH) inhibitor. 3-​Dehydrotrametenolic acid promotes adipocyte differentiation in vitro and acts as an insulin sensitizer in vivo. 3-​Dehydrotrametenolic acid induces apoptosis and has anticancer activity[1][2].

  • CAS Number: 29220-16-4
  • MF: C30H46O3
  • MW: 454.684
  • Catalog: Apoptosis
  • Density: 1.08±0.1 g/cm3
  • Boiling Point: 585.4±50.0 °C at 760 mmHg
  • Melting Point: 257-259 ºC
  • Flash Point: 321.9±26.6 °C

Gamitrinib TPP

Gamitrinib TPP is a GA mitochondrial matrix inhibitor. Gamitrinib TPP is offered as the hexafluorophosphate salt (Cat# HY-102007A).

  • CAS Number: 1131626-46-4
  • MF: C52H65N3O8P
  • MW: 891.059999999999
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FR234938

FR234938 is a non-nucleoside adenosine deaminase inhibitor with an IC50 of 17 nM for recombinant human adenosine deaminase enzyme. FR234938 has anti-rheumatic and anti-inflammatory effects[1].

  • CAS Number: 256461-79-7
  • MF: C19H21N3O2
  • MW: 323.39
  • Catalog: Adenosine Deaminase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AZD9898

AZD9898 is an orally active leukotriene-C4 synthetase (LTC4S, glutathione S-transferase II) inhibitor, with an IC50 of 0.28 nM. AZD9898 mitigates the GABA binding and hepatic toxicity signal. AZD9898 has the potential to treat asthma[1].

  • CAS Number: 2042347-69-1
  • MF: C20H19ClF3N3O4
  • MW: 457.83
  • Catalog: Gutathione S-transferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

fludrocortisone

Fludrocortisone, a synthetic mineralocorticoid with anti-inflammatory activity.

  • CAS Number: 127-31-1
  • MF: C21H29FO5
  • MW: 380.450
  • Catalog: Mineralocorticoid Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 564.7±50.0 °C at 760 mmHg
  • Melting Point: 208-212ºC
  • Flash Point: 295.3±30.1 °C

Racecadotril

Racecadotril (acetorphan), a potent enkephalinase inhibitor (IC50= 4.5 uM), protects endogenous enkephalins from degradation. IC50 value: 4.5 uMTarget: EnkephalinaseRacecadotril is a peripherally acting enkephalinase inhibitor with an IC50 of 4.5 uM. Unlike other medications used to treat diarrhea, which reduce intestinal motility, Racecadotril has an antisecretory effect-it reduces the secretion of water and electrolytes into the intestine. A small randomized controlled trial found Racecadotril to significantly reduce the duration and volume of watery diarrhea in children when given as an adjunct to oral rehydration therapy.

  • CAS Number: 81110-73-8
  • MF: C21H23NO4S
  • MW: 385.477
  • Catalog: Neprilysin
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 574.5±50.0 °C at 760 mmHg
  • Melting Point: 89ºC
  • Flash Point: 301.2±30.1 °C

Equisetin

Equisetin is an N-methylserine-derived acyl tetramic acid isolated from a terrestrial fungus Fusarium equiseti NRRL 5537[1]. Equisetin is a tetramate-containing natural product with antibiotic and cytotoxic activity[2]. Equisetin inhibits the growth of Gram-positive bacteria and HIV-1 integrase activity but shows no activity against Gram-negative bacteria[3]. Equisetin is a Quorum-sensing inhibitor (QSI) that attenuates QS-regulated virulence phenotypes in P. aeruginosa without affecting the growth of bacterias, serves as a leading compound for the treatment of P. aeruginosa infections[4].

  • CAS Number: 57749-43-6
  • MF: C22H31NO4
  • MW: 373.48600
  • Catalog: HIV Integrase
  • Density: 1.187 g/cm3
  • Boiling Point: 513.6ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 264.4ºC

Methyl icosanoate

Methyl arachidate (Methyl eicosanoate), a natural compound, is a leukotriene A4 hydrolase (LTA4H) inhibitor[1].

  • CAS Number: 1120-28-1
  • MF: C21H42O2
  • MW: 326.557
  • Catalog: Aminopeptidase
  • Density: 0.8633 g/cm3 (20 ºC)
  • Boiling Point: 375.0±5.0 °C at 760 mmHg
  • Melting Point: 45-48 °C(lit.)
  • Flash Point: 184.2±7.5 °C

Orlistat

Orlistat is a lipase inhibitor for obesity management that acts by inhibiting the absorption of dietary fats.

  • CAS Number: 96829-58-2
  • MF: C29H53NO5
  • MW: 495.735
  • Catalog: Apoptosis
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 615.9±30.0 °C at 760 mmHg
  • Melting Point: <50ºC
  • Flash Point: 326.3±24.6 °C

Xanthine oxidase-IN-7

Xanthine oxidase-IN-7 (compound1h) is a potent andorally active XO (xanthine oxidase) inhibitor with an IC50 of 0.36 µM. Xanthine oxidase-IN-7 effectively reduces serum uric acid levels. Xanthine oxidase-IN-7 has the potential for the research of hyperuricemia and gout[1].

  • CAS Number: 2411698-59-2
  • MF: C16H14N4O2
  • MW: 294.31
  • Catalog: Xanthine Oxidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Isavuconazole

Isavuconazole is a moderate inhibitor of CYP3A4 and a water-soluble triazole with broad-spectrum antifungal activity.

  • CAS Number: 241479-67-4
  • MF: C22H17F2N5OS
  • MW: 437.46500
  • Catalog: Fungal
  • Density: 1.38
  • Boiling Point: 678ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 363.8ºC

H-Cys-Thr-Thr-His-Trp-Gly-Phe-Thr-Leu-Cys-OH (Disulfide bond)

CTTHWGFTLC, CYCLIC is a cyclic peptide inhibitor for matrix metalloproteinases MMP-2 and MMP-9[1].

  • CAS Number: 244082-19-7
  • MF: C52H71N13O14S2
  • MW: 1166.33
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HSP-990

NVP-HSP990 is a potent and selective Hsp90 inhibitor, with IC50 values of 0.6, 0.8, and 8.5 nM for Hsp90α, Hsp90β, and Grp94, respectively.

  • CAS Number: 934343-74-5
  • MF: C20H18FN5O2
  • MW: 379.388
  • Catalog: HSP
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Zifcasiran

Zifcasiran is a hypoxia-inducible factor (HIF) synthesis reducer. Zifcasiran shows antitumor activities and can be used in advanced renal cell carcinoma research[1][2].

  • CAS Number: 2437257-11-7
  • MF: C737H972F20N211O349P43S8
  • MW: 20339.13
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A