Tag: M.W=400-450

Maekawa, Ai published the artcileCamostat mesilate inhibits prostasin activity and reduces blood pressure and renal injury in salt-sensitive hypertension, Safety of 2-(4-((4-Guanidinobenzoyl)oxy)phenyl)acetic acid methanesulfonic acid salt, the publication is Journal of Hypertension (2009), 27(1), 181-189, database is CAplus and MEDLINE.

Prostasin, a glycosylphosphatidylinositol-anchored serine protease, regulates epithelial sodium channel (ENaC) activity. Sodium reabsorption through ENaC in distal nephron segments is a rate-limiting step in transepithelial sodium transport. Recently, proteolytic cleavage of ENaC subunits by prostasin has been shown to activate ENaC. Therefore, we hypothesized that serine protease inhibitors could inhibit ENaC activity in the kidney, leading to a decrease in blood pressure. We investigated the effects of camostat mesilate, a synthetic serine protease inhibitor, and FOY-251, an active metabolite of camostat mesilate, on sodium transport in the mouse cortical collecting duct cell line (M-1 cells) and on blood pressure in Dahl salt-sensitive rats. Treatment with camostat mesilate or FOY-251 decreased equivalent current (Ieq) in M-1 cells in a dose-dependent manner and inhibited the protease activity of prostasin in vitro. Silencing of the prostasin gene also reduced equivalent current in M-1 cells. The expression level of prostasin protein was not changed by application of camostat mesilate or FOY-251 to M-1 cells. Oral administration of camostat mesilate to Dahl salt-sensitive rats fed a high-salt diet resulted in a significant decrease in blood pressure with elevation of the urinary Na/K ratio, decrease in serum creatinine, reduction in urinary protein excretion, and improvement of renal injury markers such as collagen 1, collagen 3, transforming growth factor-¦Â1, and nephrin. These findings suggest that camostat mesilate can decrease ENaC activity in M-1 cells probably through the inhibition of prostasin activity, and that camostat mesilate can have beneficial effects on both hypertension and kidney injury in Dahl salt-sensitive rats. Camostat mesilate might represent a new class of antihypertensive drugs with renoprotective effects in patients with salt-sensitive hypertension.

Journal of Hypertension published new progress about 71079-09-9. 71079-09-9 belongs to catalysis-chemistry, auxiliary class Salt,Carboxylic acid,Carbamidine,Amine,Benzene,Ester,Protease,Ser/Thr Protease, name is 2-(4-((4-Guanidinobenzoyl)oxy)phenyl)acetic acid methanesulfonic acid salt, and the molecular formula is C17H19N3O7S, Safety of 2-(4-((4-Guanidinobenzoyl)oxy)phenyl)acetic acid methanesulfonic acid salt.

Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia

Albarazanji, Kamal published the artcileIntestinal serine protease inhibition increases FGF21 and improves metabolism in obese mice, HPLC of Formula: 71079-09-9, the publication is American Journal of Physiology (2019), 316(5), G653-G667, database is CAplus and MEDLINE.

Trypsin is the major serine protease responsible for intestinal protein digestion. An inhibitor, camostat (CS), reduced weight gain, hyperglycemia, and dyslipidemia in obese rats; however, the mechanisms for these are largely unknown. We reasoned that CS creates an apparent dietary protein restriction, which is known to increase hepatic fibroblast growth factor 21 (FGF21). Therefore, metabolic responses to CS and a gut-restricted CS metabolite, FOY-251, were measured in mice. Food intake, body weight, blood glucose, branched-chain amino acids (LC/MS), hormone levels (ELISA), liver pathol. (histol.), and transcriptional changes (qRT-PCR) were measured in ob/ob, lean and diet-induced obese (DIO) C57BL/6 mice. In ob/ob mice, CS in chow (9-69 mg/kg) or FOY-251 (46 mg/kg) reduced food intake and body weight gain to a similar extent as pair-fed mice. CS decreased blood glucose, liver weight, and lipidosis and increased FGF21 gene transcription and plasma levels. In lean mice, CS increased liver FGF21 mRNA and plasma levels. Relative to pair feeding, FOY-251 also increased plasma FGF21 and induced liver FGF21 and integrated stress response (ISR) transcription. In DIO mice, FOY-251 (100 mg/kg po) did not alter peak glucose levels but reduced the AUC of the glucose excursion in response to an oral glucose challenge. FOY-251 increased plasma FGF21 levels. In addition to previously reported satiety-dependent (cholecystokinin-mediated) actions, intestinal trypsin inhibition engages non-satiety-related pathways in both leptin-deficient and DIO mice. This novel mechanism improves metabolism by a liver-integrated stress response and increased FGF21 expression levels in mice.

American Journal of Physiology published new progress about 71079-09-9. 71079-09-9 belongs to catalysis-chemistry, auxiliary class Salt,Carboxylic acid,Carbamidine,Amine,Benzene,Ester,Protease,Ser/Thr Protease, name is 2-(4-((4-Guanidinobenzoyl)oxy)phenyl)acetic acid methanesulfonic acid salt, and the molecular formula is C17H19N3O7S, HPLC of Formula: 71079-09-9.

Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia

Midgley, I. published the artcileMetabolic fate of ¹⁴C-camostat mesylate in man, rat and dog after intravenous administration, Category: catalysis-chemistry, the publication is Xenobiotica (1994), 24(1), 79-92, database is CAplus and MEDLINE.

The metabolic fate of N,N-dimethylcarbamoylmethyl 4-(4-guanidino[¹⁴C]benzoyloxy)phenylacetate methanesulfonate (¹⁴C-camostat mesylate) was investigated after i.v. administration to man (12-h infusion), and to rat and dog (bolus injection). Renal excretion (mainly in 24h) accounted for at least 80% dose in all three species, and the only two important metabolites were identified as 4-(4-guanidinobenzoyloxy)phenylacetic acid (GBPA) and 4-guanidinobenzoic acid (GBA). The parent drug was not detected in human plasma either during or after infusion of ¹⁴C-camostat mesylate owing to rapid hydrolysis of the side-chain ester group (t_1/2 < 1 min). Steady-state levels of both GBPA and GBA in plasma were apparently attained by the end of the infusion period. Mean terminal half-life, systemic clearance and apparent volume of distribution at steady-state of GBPA in man were 1.0 h, 6.4 mL/min per kg and 0.381/kg, resp., and the corresponding values for GBA were 2.4 h, 4.7 mL/min per kg and 1.01/kg resp. Radioactivity was rapidly distributed to most tissues after bolus i.v. doses of ¹⁴C-camostat mesylate to rats and dogs, with highest levels being associated with the liver and kidney, the two main organs of drug elimination. Concentrations in the pancreas, a possible site for drug action, were generally lower than those in plasma.

Xenobiotica published new progress about 71079-09-9. 71079-09-9 belongs to catalysis-chemistry, auxiliary class Salt,Carboxylic acid,Carbamidine,Amine,Benzene,Ester,Protease,Ser/Thr Protease, name is 2-(4-((4-Guanidinobenzoyl)oxy)phenyl)acetic acid methanesulfonic acid salt, and the molecular formula is C17H19N3O7S, Category: catalysis-chemistry.

Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia

Hoffmann, Markus published the artcileCamostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity, Recommanded Product: 2-(4-((4-Guanidinobenzoyl)oxy)phenyl)acetic acid methanesulfonic acid salt, the publication is EBioMedicine (2021), 103255, database is CAplus and MEDLINE.

Antivirals are needed to combat the COVID-19 pandemic, which is caused by SARS-CoV-2. The clin.-proven protease inhibitor Camostat mesylate inhibits SARS-CoV-2 infection by blocking the virus-activating host cell protease TMPRSS2. However, antiviral activity of Camostat mesylate metabolites and potential viral resistance have not been analyzed. Moreover, antiviral activity of Camostat mesylate in human lung tissue remains to be demonstrated. We used recombinant TMPRSS2, reporter particles bearing the spike protein of SARS-CoV-2 or authentic SARS-CoV-2 to assess inhibition of TMPRSS2 and viral entry, resp., by Camostat mesylate and its metabolite GBPA. We show that several TMPRSS2-related proteases activate SARS-CoV-2 and that two, TMPRSS11D and TMPRSS13, are robustly expressed in the upper respiratory tract. However, entry mediated by these proteases was blocked by Camostat mesylate. The Camostat metabolite GBPA inhibited recombinant TMPRSS2 with reduced efficiency as compared to Camostat mesylate. In contrast, both inhibitors exhibited similar antiviral activity and this correlated with the rapid conversion of Camostat mesylate into GBPA in the presence of serum. Finally, Camostat mesylate and GBPA blocked SARS-CoV-2 spread in human lung tissue ex vivo and the related protease inhibitor Nafamostat mesylate exerted augmented antiviral activity. Our results suggest that SARS-CoV-2 can use TMPRSS2 and closely related proteases for spread in the upper respiratory tract and that spread in the human lung can be blocked by Camostat mesylate and its metabolite GBPA. NIH, Damon Runyon Foundation, ACS, NYCT, DFG, EU, Berlin Mathematics center MATH+, BMBF, Lower Saxony, Lundbeck Foundation, Novo Nordisk Foundation.

EBioMedicine published new progress about 71079-09-9. 71079-09-9 belongs to catalysis-chemistry, auxiliary class Salt,Carboxylic acid,Carbamidine,Amine,Benzene,Ester,Protease,Ser/Thr Protease, name is 2-(4-((4-Guanidinobenzoyl)oxy)phenyl)acetic acid methanesulfonic acid salt, and the molecular formula is C17H19N3O7S, Recommanded Product: 2-(4-((4-Guanidinobenzoyl)oxy)phenyl)acetic acid methanesulfonic acid salt.

Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia

Chan, Leslie W. published the artcileSelective Permeabilization of Gram-Negative Bacterial Membranes Using Multivalent Peptide Constructs for Antibiotic Sensitization, Name: Dbco-maleimide, the publication is ACS Infectious Diseases (2021), 7(4), 721-732, database is CAplus and MEDLINE.

The drug-impermeable bacterial membrane in Gram-neg. pathogens limits antibiotic access to intracellular drug targets. To expand our rapidly waning antibiotic arsenal, one approach is to improve the intracellular delivery of drugs with historically poor accumulation in Gram-neg. bacteria. To do so, we engineered macromol. potentiators to permeabilize the Gram-neg. membrane to facilitate drug influx. Potentiators, known as WD40, were synthesized by grafting multiple copies of a cationic ¦Á-helical antimicrobial peptide, WLBU2, onto a dextran polymer scaffold. WD40 enabled drug uptake in the model pathogen P. aeruginosa, a capability that was not observed with unmodified WLBU2 peptide. WD40 was able to reduce min. inhibitory concentrations of a drug panel by up to 3 orders of magnitude. Hydrophobic and highly three-dimensional antibiotics exhibited the greatest potentiation. Antibiotic activity was potentiated in several clin. strains and resulted in sensitization of drug-resistant strains to rifampin, a drug not previously used for Gram-neg. infections.

ACS Infectious Diseases published new progress about 1395786-30-7. 1395786-30-7 belongs to catalysis-chemistry, auxiliary class Inhibitor, name is Dbco-maleimide, and the molecular formula is C25H21N3O4, Name: Dbco-maleimide.

Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia

Kitagawa, Motoji published the artcilePancreatic and biliary excretion of camostat in dogs, COA of Formula: C17H19N3O7S, the publication is Digestion (1988), 39(4), 204-9, database is CAplus and MEDLINE.

To confirm whether camostat (Foy-305) is excreted into bile or pancreatic juice, camostat (5 mg/kg/h) was given i.v. to dogs with pancreatic or biliary fistulae. Camostat and its active metabolite (Foy-251) (I) in bile and pancreatic juice were measured by HPLC and by their trypsin-inhibitory activity. Camostat did not alter the exocrine pancreatic secretion of fluid, bicarbonate, protein or trypsin stimulated by secretin and caerulein. Camostat and its active metabolite were detected in bile by HPLC and trypsin-inhibitory activity (the mean excretion rate was 1.3% of the i.v. dose of camostat), but they were not detectable in pancreatic juice. In conclusion, camostat and its active metabolite were excreted into bile but not into pancreatic juice.

Digestion published new progress about 71079-09-9. 71079-09-9 belongs to catalysis-chemistry, auxiliary class Salt,Carboxylic acid,Carbamidine,Amine,Benzene,Ester,Protease,Ser/Thr Protease, name is 2-(4-((4-Guanidinobenzoyl)oxy)phenyl)acetic acid methanesulfonic acid salt, and the molecular formula is C17H19N3O7S, COA of Formula: C17H19N3O7S.

Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia

Nakamura, Ryuji published the artcileOral camostat mesilate administration on alkaline reflux esophagitis in an experimental animal model, Synthetic Route of 71079-09-9, the publication is Iwate Igaku Zasshi (1999), 50(Suppl.), 653-659, database is CAplus.

Following total gastrectomy and esophagojejunostomy in an end-to-side fashion, tabs of a synthetic proteinase inhibitor, camostat mesilate, were fed to 15 dogs via cervical esophagostomy. A 67% decrease in trypsin activity was observed in duodenal juice aspirated 30 min after administration. The suppression lasted 90 min. Administration of camostat 3 times per day for 2 wk (n = 5) failed to significantly improve erosive esophagitis noted by esophagoscopy, although a tendency of hemostasis of hemorrhagic erosion has been induced. In postoperative alk. reflux esophagitis, oral camostat administration alone is insufficient to protect the esophageal mucosa. Bile acid or other constituents of reflux must also be neutralized to improve the clin. condition.

Iwate Igaku Zasshi published new progress about 71079-09-9. 71079-09-9 belongs to catalysis-chemistry, auxiliary class Salt,Carboxylic acid,Carbamidine,Amine,Benzene,Ester,Protease,Ser/Thr Protease, name is 2-(4-((4-Guanidinobenzoyl)oxy)phenyl)acetic acid methanesulfonic acid salt, and the molecular formula is C17H19N3O7S, Synthetic Route of 71079-09-9.

Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia

Cheloha, Ross W. published the artcileImproved GPCR ligands from nanobody tethering, Name: Dbco-maleimide, the publication is Nature Communications (2020), 11(1), 2087, database is CAplus and MEDLINE.

Abstract: Antibodies conjugated to bioactive compounds allow targeted delivery of therapeutics to cell types of choice based on that antibody’s specificity. Here we develop a new type of conjugate that consists of a nanobody and a peptidic ligand for a G protein-coupled receptor (GPCR), fused via their C-termini. We address activation of parathyroid hormone receptor-1 (PTHR1) and improve the signaling activity and specificity of otherwise poorly active N-terminal peptide fragments of PTH by conjugating them to nanobodies (VHHs) that recognize PTHR1. These C-to-C conjugates show biol. activity superior to that of the parent fragment peptide in vitro. In an exploratory experiment in mice, a VHH-PTH peptide conjugate showed biol. activity, whereas the corresponding free peptide did not. The lead conjugate also possesses selectivity for PTHR1 superior to that of PTH(1-34). This design approach, dubbed “conjugation of ligands and antibodies for membrane proteins” (CLAMP), can yield ligands with high potency and specificity.

Nature Communications published new progress about 1395786-30-7. 1395786-30-7 belongs to catalysis-chemistry, auxiliary class Inhibitor, name is Dbco-maleimide, and the molecular formula is C25H21N3O4, Name: Dbco-maleimide.

Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia

Evans, Helen L. published the artcileBioorthogonal chemistry for ⁶⁸Ga radiolabelling of DOTA-containing compounds, Formula: C25H21N3O4, the publication is Journal of Labelled Compounds and Radiopharmaceuticals (2014), 57(4), 291-297, database is CAplus and MEDLINE.

Copper-catalyzed ‘click’ chem. is a highly used technique for radiolabeling small mols. and peptides for imaging applications. The usefulness of these reactions falls short, however, when metal catalysis is not a practically viable route; such as when using metal chelates as radioligands. Here, the authors describe a method for carrying out ‘click-type’ radiochem. in the presence of DOTA chelates, by combining ⁶⁸Ga radiolabeling techniques with well-established bioorthogonal reactions, which do not rely upon metal catalysis.

Journal of Labelled Compounds and Radiopharmaceuticals published new progress about 1395786-30-7. 1395786-30-7 belongs to catalysis-chemistry, auxiliary class Inhibitor, name is Dbco-maleimide, and the molecular formula is C25H21N3O4, Formula: C25H21N3O4.

Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia

Cordonnier, Axel published the artcileSynthesis and in vitro preliminary evaluation of prostate-specific membrane antigen targeted upconversion nanoparticles as a first step towards radio/fluorescence-guided surgery of prostate cancer, HPLC of Formula: 1395786-30-7, the publication is Journal of Materials Chemistry B: Materials for Biology and Medicine (2021), 9(36), 7423-7434, database is CAplus and MEDLINE.

Over the last decade, upconversion nanoparticles (UCNP) have been widely investigated in nanomedicine due to their high potential as imaging agents in the near-IR (NIR) optical window of biol. tissues. Here, we successfully develop active targeted UCNP as potential probes for dual NIR-NIR fluorescence and radioactive-guided surgery of prostate-specific membrane antigen (PSMA)(+) prostate cancers. We designed a one-pot thermolysis synthesis method to obtain oleic acid-coated spherical NaYF₄:Yb,Tm@NaYF₄ core/shell UCNP with narrow particle size distribution (30.0 ¡À 0.1 nm, as estimated by SAXS anal.) and efficient upconversion luminescence. Polyethylene glycol (PEG) ligands bearing different anchoring groups (phosphate, bis- and tetra-phosphonate-based) were synthesized and used to hydrophilize the UCNP. DLS studies led to the selection of a tetra-phosphonate PEG(2000) ligand affording water-dispersible UCNP with sustained colloidal stability in several aqueous media. PSMA-targeting ligands (i.e., glutamate-urea-lysine derivatives called KuEs) and fluorescent or radiolabeled prosthetic groups were grafted onto the UCNP surface by strain-promoted azide-alkyne cycloaddition (SPAAC). These UCNP, coated with 10 or 100% surface d. of KuE ligands, did not induce cytotoxicity over 24 h incubation in LNCaP-Luc or PC3-Luc prostate cancer cell lines or in human fibroblasts for any of the concentrations evaluated. Competitive binding assays and flow cytometry demonstrated the excellent affinity of UCNP@KuE for PSMA-pos. LNCaP-Luc cells compared with non-targeted UCNP@CO₂H. Furthermore, the binding of UCNP@KuE to prostate tumor cells was pos. correlated with the surface d. of PSMA-targeting ligands and maintained after ¹²⁵I-radiolabelling. Finally, a preliminary biodistribution study in LNCaP-Luc-bearing mice demonstrated the radiochem. stability of non-targeted [^125I]UCNP paving the way for future in vivo assessments.

Journal of Materials Chemistry B: Materials for Biology and Medicine published new progress about 1395786-30-7. 1395786-30-7 belongs to catalysis-chemistry, auxiliary class Inhibitor, name is Dbco-maleimide, and the molecular formula is C25H21N3O4, HPLC of Formula: 1395786-30-7.

Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia