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 >
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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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Asundexian

Asundexian (BAY 2433334) is an orally active coagulation factor Xia (FXIa) inhibitor. Asundexian binds directly, potently, and reversibly to the active site of FXIa and thereby inhibits its activity. Asundexian inhibits human FXIa in buffer with an IC50 of 1 nM[1].

  • CAS Number: 2064121-65-7
  • MF: C26H21ClF4N6O4
  • MW: 592.93
  • Catalog: Factor Xa
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

G 28UCM

UCM05 (G28UCM) is a potent inhibitor of fatty acid synthase (FASN) shows activity against HER2+ breast cancer xenografts and is active in anti-HER2 drug-resistant cell lines[1]. UCM05 is a Filamentous temperature-sensitive protein Z (FtsZ) inhibitor and inhibits the growth of the Gram-positive bacterium B. subtilis with MIC values of 100 μM but lack activity on the Gram-negative bacterium E. coli[2].

  • CAS Number: 1094451-90-7
  • MF: C24H16O10
  • MW: 464.378
  • Catalog: Bacterial
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 895.1±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 313.3±27.8 °C

Z-Gly-Gly-Phe-chloromethylketone

Z-GGF-CMK is a protease inhibitor, inhibits ClpP1P2 and proteasome. Z-GGF-CMK exhibits cytotoxic activity against HepG2 cells with a CC50 value of 125 μM[1].

  • CAS Number: 35172-59-9
  • MF: C22H24ClN3O5
  • MW: 445.90
  • Catalog: Proteasome
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Enpp-1-IN-15

Enpp-1-IN-15 (Compound 88a) is an Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (Enpp-1) Inhibitor, with a Ki value of 0.00586 nM[1].

  • CAS Number: 2756218-99-0
  • MF: C16H20N6O2S
  • MW: 360.43
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NEP-In-1

NEP-IN-1 is a neutral endopeptidase (NEP) inhibitor with IC50 of 2 nM for dNEP.

  • CAS Number: 465527-94-0
  • MF: C21H30ClNO4
  • MW: 395.92
  • Catalog: Neprilysin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tipranavir-d4

Tipranavir-d4 (PNU-140690-d4) is the deuterium labeled Tipranavir. Tipranavir (PNU-140690) inhibits the enzymatic activity and dimerization of HIV-1 protease, exerts potent activity against multi-protease inhibitor (PI)-resistant HIV-1 isolates with IC50s of 66-410 nM[1][2]. Tipranavir inhibits SARS-CoV-2 3CLpro activity[3].

  • CAS Number: 1217819-15-2
  • MF: C31H33F3N2O5S
  • MW: 602.664
  • Catalog: HIV
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 712.3±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 384.6±35.7 °C

Cirsimarin

Cirsimarin is a potent antilipogenic flavonoid isolated from Microtea debilis. Cirsimarin exerts potent antilipogenic effect and decreases adipose tissue deposition in mice. The lipolytic activity of Cirsimarin resulting from both its antagonist activity on adenosin A1 receptor and its inhibitory effect on phosphodiesterase[1].

  • CAS Number: 13020-19-4
  • MF: C23H24O11
  • MW: 476.43000
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.523g/cm3
  • Boiling Point: 767.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 265.8ºC

RMC-3943

RMC-3943 is an allosteric SHP2 inhibitor (inhibition of full-length SHP2 in biochemical assay, IC50 = 2.19 nM)[1].

  • CAS Number: 1801764-60-2
  • MF: C18H22Cl2N6S
  • MW: 425.38
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-Aminobenzenesulfonamide

2-Aminobenzenesulfonamide is a carbonic anhydrase IX inhibitor.

  • CAS Number: 3306-62-5
  • MF: C6H8N2O2S
  • MW: 172.205
  • Catalog: Carbonic Anhydrase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 392.7±44.0 °C at 760 mmHg
  • Melting Point: 155-157 °C(lit.)
  • Flash Point: 191.3±28.4 °C

SAP2-IN-1

SAP2-IN-1 is a secreted aspartic protease 2 (SAP2) inhibitor and has potent SAP2 inhibitory activity with an IC50 value of 0.92 μM. SAP2-IN-1 also is a virulence factor inhibitor and is inactive in vitro. SAP2-IN-1 can be used for the research of infection[1].

  • CAS Number: 2512847-37-7
  • MF: C34H29NO7
  • MW: 563.60
  • Catalog: Proteasome
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Vinpocetine

Vinpocetine(Cavinton; Ethyl apovincaminate) is a selective for PDE1 (IC50 = 21 μM). Also blocks voltage-gated Na+ channels.IC50 value:Target: PDE1; Na+ channel

  • CAS Number: 42971-09-5
  • MF: C22H26N2O2
  • MW: 350.454
  • Catalog: Sodium Channel
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 419.5±45.0 °C at 760 mmHg
  • Melting Point: 147-153ºC dec
  • Flash Point: 207.5±28.7 °C

5-Hydroxyfisetin

Robinetin (3,3',4',5',7-Pentahydroxyflavone), a naturally occurring flavonoid with remarkable ‘two color’ intrinsic fluorescence properties, has antifungal, antiviral, antibacterial, antimutagenesis, and antioxidant activity. Robinetin also can inhibit lipid peroxidation and protein glycosylation[1][2][3][4][5].

  • CAS Number: 490-31-3
  • MF: C15H10O7
  • MW: 302.236
  • Catalog: Bacterial
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: 669.9±55.0 °C at 760 mmHg
  • Melting Point: 326-328ºC
  • Flash Point: 258.6±25.0 °C

Nafamostat (hydrochloride)

Nafamostat hydrochloride, a synthetic serine protease inhibitor, is an anticoagulant.Target: Serine ProteaseTranilast (FUT-175) is an antiallergic drug for bronchial asthma. It has been used for the treatment of allergic disorders such as asthma, allergic rhinitis and atopic dermatitis. It has also been investigated for use as an antiproliferative drug on drug-eluting stents.A 20-40 mg/h dose of FUT-175 prolonged coagulation time sufficiently in the instrumental blood of the extracorporeal circuit but not in the systemic blood. Its anticoagulant activity decreased immediately after hemodialysis. Therefore, we could manage all patients without any bleeding trouble during hemodialysis with FUT-175 as an anticoagulant. Although there were side effects of FUT-175, such as nausea, vomiting, itching and eruption, they were not serious, and FUT-175 could be administered without interruption. FUT-175 seems to be useful as an anticoagulant during hemodialysis for patients susceptible to bleeding.

  • CAS Number: 80251-32-7
  • MF: C19H19Cl2N5O2
  • MW: 420.29
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PP5-IN-1

PP5-IN-1 (Compound P053) is a competitive inhibitor of Serine/threonine protein phosphatase-5 (PP5) that binds to its catalytic domain and causes apoptosis in renal cancer[1].

  • CAS Number: 1022417-69-1
  • MF: C18H18N2O3S
  • MW: 342.41
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

T 0156 hydrochloride

T-0156 is a potent and selective phosphodiesterase type 5 (PDE5) inhibitor. T-0156 specifically inhibits the hydrolysis of cyclic guanosine monophosphate (cGMP) by PDE5 in a competitive manner (IC50=0.23 nM). T-0156 inhibits PDE6 (IC50=56 nM) and has low potencies against PDE1, PDE2, PDE3, and PDE4 (IC50>10 μM). T-0156 enhances the nitric oxide (NO)/cGMP pathway[1].

  • CAS Number: 324572-93-2
  • MF: C31H30ClN5O7
  • MW: 620.05
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Galeterone

TOK-001 is a multifunctional antiandrogen and CYP17 inhibitor (IC50=47 nM) in castration resistant prostate cancer (CRPC).

  • CAS Number: 851983-85-2
  • MF: C26H32N2O
  • MW: 388.545
  • Catalog: Cytochrome P450
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 564.5±60.0 °C at 760 mmHg
  • Melting Point: 189-190℃
  • Flash Point: 295.2±32.9 °C

CMX-2043

CMX-2043 is a novel analogue of α-Lipoic Acid (HY-N0492). CMX-2043 is effective in antioxidant effect, activation of insulin receptor kinase, soluble tyrosine kinase, and Akt phosphorylation. CMX-2043 shows protection against ischemia-reperfusion injury (IRI) in rat model[1][2].

  • CAS Number: 910627-26-8
  • MF: C16H26N2O6S2
  • MW: 406.52
  • Catalog: Tyrosinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CALP2 TFA

CALP2 is a calmodulin (CaM) antagonist ( (Kd of 7.9 µM)) with high affinity for binding to the CaM EF-hand/Ca2+-binding site. CALP2 inhibits CaM-dependent phosphodiesterase activity and increases intracellular Ca2+ concentrations. CALP2 potently inhibits of adhesion and degranulation. CALP2 is also a strong activator of alveolar macrophages[1][2][3][4].

  • CAS Number: 261969-04-4
  • MF: C68H104N14O13S
  • MW: 1357.70000
  • Catalog: Calcium Channel
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IDO-IN-2

IDO-IN-2 is an IDO inhibitor extracted from patent WO/2015031295 A1, compound example 1, has IC50 values of 0.068 μM in HeLa cell and 0.16 μM in HEK293 cell.

  • CAS Number: 1668565-74-9
  • MF: C29H35N7O
  • MW: 497.63
  • Catalog: Indoleamine 2,3-Dioxygenase (IDO)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ubiquitination-IN-1

Ubiquitination-IN-1 (compound 24) is a ubiquitination and Cksl-Skp2 protein-protein interaction (IC50=0.17 μM) inhibitor. Ubiquitination-IN-1 increases levels of p27. Ubiquitination-IN-1 can be used to treat disease by blocking the degradation of tumor suppressors[1].

  • CAS Number: 1819330-15-8
  • MF: C21H14F3N3O2S
  • MW: 429.41
  • Catalog: E1/E2/E3 Enzyme
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-Chloro-N-(3,4-dimethoxybenzyl)acetamide

DKM 2-93 is a relatively selective inhibitor of UBA5 with an IC50 of 430 μM.

  • CAS Number: 65836-72-8
  • MF: C11H14ClNO3
  • MW: 243.68700
  • Catalog: E1/E2/E3 Enzyme
  • Density: 1.194g/cm3
  • Boiling Point: 425.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 211.3ºC

GM 6001

Ilomastat (Galardin; GM6001) is a broad spectrum matrix metalloprotease (MMP) inhibitor, with Ki of 0.4 nM, 0.5 nM, 27 nM, 3.7 nM, 0.1 nM, 0.2 nM, 3.6 nM, 13.4 nM, 0.36 nM for MMP-1/2/3/7/8/9/12/14/26, respectively.

  • CAS Number: 142880-36-2
  • MF: C20H28N4O4
  • MW: 388.461
  • Catalog: MMP
  • Density: 1.228±0.06 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GPLGIAGQ

GPLGIAGQ, a MMP2-cleavable polypeptide, is used as a stimulus-sensitive linker in both liposomal and micellar nanocarriers for MMP2-triggered tumor targeting. GPLGIAGQ can be used to synthesis unique MMP2-targeted photosensitizer in photodynamic therapy (PDT)[1][2][3].

  • CAS Number: 109053-09-0
  • MF: C31H53N9O10
  • MW: 711.81
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VCH-916

VCH-916 is a novel nonnucleoside HCV NS5B polymerase inhibitor.IC50 Value: Target: HCVVCH-916 is a novel allosteric inhibitor of HCV NS5B polymerase. The RNA-dependent RNA polymerase (NS5B) of HCV is one of the attractive validated targets for development of new drugs to block HCV infection. VCH-916 is currently being evaluated for safety/tolerability, pharmacokinetics and anti-viral efficacy in chronically infected HCV patient.

  • CAS Number: 1200133-34-1
  • MF: C26H36KNO4S
  • MW: 497.732
  • Catalog: HCV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Zileuton-d4

Zileuton-d4 (A 64077-d4) is the deuterium labeled Zileuton. Zileuton (A 64077) is a potent and selective inhibitor of 5-lipoxygenase with antiasthmatic properties[1][2].

  • CAS Number: 1189878-76-9
  • MF: C11H8D4N2O2S
  • MW: 240.31500
  • Catalog: Ferroptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sampatrilat

Sampatrilat (UK-81252) is a potent and orally active vasopeptidase inhibitor of ACE and neutral endopeptidase (NEP). Sampatrilat inhibits C-domain ACE (Ki=13.8 nM) 12.4-fold more potent than that for the N-domain (Ki=171.9 nM). Sampatrilat (UK-81252) can be used for the study of chronic heart failure and blood pressure regulation[1][2].

  • CAS Number: 129981-36-8
  • MF: C26H40N4O9S
  • MW: 584.68200
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: 1.343g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

WNK-IN-11 D3

WNK-IN-11 D3 is an orally active, selective and potent With-No-Lysine (WNK) kinase inhibitor. WNK-IN-11 D3 is effective at regulating cardiovascular homeostasis[1].

  • CAS Number: 2123483-49-6
  • MF: C21H18D3Cl2N5OS
  • MW: 465.41
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sal003

Sal003 is a potent cell-permeable analog of the eIF2α phosphatase inhibitor Salubrinal with enhanced aqueous solubility.IC50 value:Target: eIF2α phosphatase inhibitorSal003 has been shown to prevent dephosphorylation of eIF-2α which has been shown to regulate the late phase of long-term potentiation (LTP) and memory (LTM). This enhanced phosphorylated state of eIF-2α is shown to prevent L-LTP and suppress memory in mice.

  • CAS Number: 1164470-53-4
  • MF: C18H15Cl4N3OS
  • MW: 463.208
  • Catalog: Phosphatase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Carbonic anhydrase

Carbonic anhydrase is ubiquitous zinc-containing metalloenzyme present in prokaryotes and eukaryotes. Carbonic anhydrase can catalyze reversible conversion of carbon dioxide to bicarbonate and protons. Carbonic anhydrase can be used for the research of cancer, glaucoma, obesity and epilepsy[1][2].

  • CAS Number: 9001-03-0
  • MF:
  • MW:
  • Catalog: Carbonic Anhydrase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nelfinavir

Nelfinavir(AG-1341) is a potent and orally bioavailable human immunodeficiency virus HIV-1 protease inhibitor (Ki=2 nM) and is widely prescribed in combination with HIV reverse transcriptase inhibitors for the treatment of HIV infection. IC50 Valur: 2 nM (Ki for HIV-1 protease) [2]Target: HIV Proteasein vitro: In vitro exposure (72 hours) of HAECs to NEL (0.25-2 μg/mL) decreased both basal (2.5-fold) and insulin-induced NO production (4- to 5-fold). NEL suppressed insulin-induced phosphorylation of both Akt and eNOS at serine residues 473 and 1177, respectively. NEL decreased tyrosine phosphorylation of IR-β, IRS-1, and PI3K. Coexposure to troglitazone (TRO; 250 nM) ameliorated the suppressive effects of NEL on insulin signaling and NO production. Coexposure to TRO also increased eNOS expression in NEL-treated HAECs [1]. AG1343 is a potent enzyme inhibitor (Ki = 2 nM) and antiviral agent (HIV-1 ED50 = 14 nM). An X-ray cocrystal structure of the enzyme-AG1343 complex reveals how the novel thiophenyl ether and phenol-amide substituents of the inhibitor interact with the S1 and S2 subsites of HIV-1 protease, respectively [2].in vivo: In vivo studies indicate that AG1343 is well absorbed orally in a variety of species and possesses favorable pharmacokinetic properties in humans [2].

  • CAS Number: 159989-64-7
  • MF: C32H45N3O4S
  • MW: 567.78
  • Catalog: HIV
  • Density: 1.22g/cm3
  • Boiling Point: 786.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 429.7ºC