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#35044590   2022/01/19 To Up

Development of a Physiologically-Based Pharmacokinetic Model for Whole-Body Disposition of MMAE Containing Antibody-Drug Conjugate in Mice.

To quantitate and mathematically characterize the whole-body pharmacokinetics (PK) of different ADC analytes following administration of an MMAE-conjugated ADC in tumor-bearing mice.
Hsuan-Ping Chang, Zhe Li, Dhaval K Shah

1744 related Products with: Development of a Physiologically-Based Pharmacokinetic Model for Whole-Body Disposition of MMAE Containing Antibody-Drug Conjugate in Mice.

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#35041905   2022/01/15 To Up

Bisphenol A-sulfate conjugate disrupts AURKA transcription and cell cycle in BeWo cytotrophoblasts.

Bisphenol A (BPA) has been shown to exhibit various toxic effects, including the induction of reproductive disorders. Generally, BPA is converted to conjugated metabolites, leading to bio-inactivation. On the other hand, the toxicity of conjugated metabolites is not fully understood. Notably, the placenta develops the sulfate-sulfatase pathway, which transports and reactivates sulfated steroids. Therefore, we investigated the potential adverse effects of the BPA-sulfate conjugate (BPA-S) on human placenta-derived BeWo cytotrophoblasts. In the present study, high-concentration BPA-S (100 μM) induced significant inhibition of BeWo growth, with effects similar to those seen with unconjugated BPA (100 μM and 100 nM). This growth inhibition was restored by treatment of the cells with an inhibitor of the organic anion-transporting peptides (OATPs) (bromosulphophthalein) or with a sulfatase (STS) inhibitor (STX64). BeWo exhibits expression of the genes encoding OATP1A2 and OATP4A1 as known sulfated steroid transporters and STS, suggesting that BPA-S suppresses cell growth activity via the sulfate-sulfatase pathway. In addition, cell cycle analysis revealed that BPA-S (100 μM) increased the fraction of cytotrophoblasts in the G2/M phases and significantly decreased the accumulation of the transcript encoding Aurora kinase A (AURKA), which is a critical regulator of cellular division. These results suggested that BPA-S triggers cell cycle arrest and inhibits proliferation of BeWo cytotrophoblasts by decreased AURKA, an effect that is mediated by the sulfate-sulfatase pathway. Overall, these findings provide insights into the reactivation of sulfated endocrine-disrupting chemicals and subsequent adverse effects.
Jumpei Fujiki, Megumi Uchida, Sakurako Tsunoda, Naoyuki Maeda, Hiroki Inoue, Hiroshi Yokota, Hidetomo Iwano

1455 related Products with: Bisphenol A-sulfate conjugate disrupts AURKA transcription and cell cycle in BeWo cytotrophoblasts.

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#35024184   2021/06/08 To Up

Hyperoside attenuates non-alcoholic fatty liver disease in rats via cholesterol metabolism and bile acid metabolism.

Non-alcoholic fatty liver disease (NAFLD) results from increased hepatic total cholesterol (TC) and total triglyceride (TG) accumulation. In our previous study, we found that rats treated with hyperoside became resistant to hepatic lipid accumulation.
Songsong Wang, Feiya Sheng, Liang Zou, Jianbo Xiao, Peng Li

1898 related Products with: Hyperoside attenuates non-alcoholic fatty liver disease in rats via cholesterol metabolism and bile acid metabolism.

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#35015702   2022/01/01 To Up

Oral estrogen leads to falsely low concentrations of estradiol in a common immunoassay.

Recently, an estradiol immunoassay manufacturer (Beckman Coulter, USA) issued an "Important Product Notice" alerting clinical laboratories their assay (Access Sensitive Estradiol) was not indicated for patients undergoing exogenous estradiol treatment. The objective of this analysis was to evaluate immunoassay bias relative to liquid chromatography tandem mass spectrometry (LC-MS/MS) in transgender women and to examine the influence of unconjugated estrone on measurements.
Lauren R Cirrincione, Bridgit O Crews, Jane A Dickerson, Matthew D Krasowski, Jessica Rongitsch, Katherine L Imborek, Zil Goldstein, Dina N Greene

2939 related Products with: Oral estrogen leads to falsely low concentrations of estradiol in a common immunoassay.

100 μg25 100 1 kit100

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#35007297   2022/01/10 To Up

Epstein-Barr Virus BGLF2 commandeers RISC to interfere with cellular miRNA function.

The Epstein-Barr virus (EBV) BGLF2 protein is a tegument protein with multiple effects on the cellular environment, including induction of SUMOylation of cellular proteins. Using affinity-purification coupled to mass-spectrometry, we identified the miRNA-Induced Silencing Complex (RISC), essential for miRNA function, as a top interactor of BGLF2. We confirmed BGLF2 interaction with the Ago2 and TNRC6 components of RISC in multiple cell lines and their co-localization in cytoplasmic bodies that also contain the stress granule marker G3BP1. In addition, BGLF2 expression led to the loss of processing bodies in multiple cell types, suggesting disruption of RISC function in mRNA regulation. Consistent with this observation, BGLF2 disrupted Ago2 association with multiple miRNAs. Using let-7 miRNAs as a model, we tested the hypothesis that BGLF2 interfered with the function of RISC in miRNA-mediated mRNA silencing. Using multiple reporter constructs with 3'UTRs containing let-7a regulated sites, we showed that BGLF2 inhibited let-7a miRNA activity dependent on these 3'UTRs, including those from SUMO transcripts which are known to be regulated by let-7 miRNAs. In keeping with these results, we showed that BGLF2 increased the cellular level of unconjugated SUMO proteins without affecting the level of SUMO transcripts. Such an increase in free SUMO is known to drive SUMOylation and would account for the effect of BGLF2 in inducing SUMOylation. We further showed that BGLF2 expression inhibited the loading of let-7 miRNAs into Ago2 proteins, and conversely, that lytic infection with EBV lacking BGLF2 resulted in increased interaction of let-7a and SUMO transcripts with Ago2, relative to WT EBV infection. Therefore, we have identified a novel role for BGLF2 as a miRNA regulator and shown that one outcome of this activity is the dysregulation of SUMO transcripts that leads to increased levels of free SUMO proteins and SUMOylation.
Ashley M Campbell, Carlos F De La Cruz Herrera, Edyta Marcon, Jack Greenblatt, Lori Frappier

2412 related Products with: Epstein-Barr Virus BGLF2 commandeers RISC to interfere with cellular miRNA function.

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#34996855   // To Up

Membrane attack complex (MAC) deposition in renal tubules is associated with interstitial fibrosis and tubular atrophy: a pilot study.

Treatment failures for lupus nephritis (LN) are high with 10%-30% of patients progressing to end-stage renal disease (ESRD) within 10 years. Interstitial fibrosis/tubular atrophy (IFTA) is a predictor of progression to ESRD. Prior studies suggest that tubulointerstitial injury secondary to proteinuria in LN is mediated by complement activation in the tubules, specifically through the membrane attack complex (MAC). This study aimed to investigate the associations between tubular MAC deposition with IFTA and proteinuria.
Shudan Wang, Ming Wu, Luis Chiriboga, Briana Zeck, Beatrice Goilav, Shuwei Wang, Alejandra Londono Jimenez, Chaim Putterman, Daniel Schwartz, James Pullman, Anna Broder, H Michael Belmont

2170 related Products with: Membrane attack complex (MAC) deposition in renal tubules is associated with interstitial fibrosis and tubular atrophy: a pilot study.

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#34992224   2022/01/06 To Up

Relation of circulating estrogens with hair relaxer and skin lightener use among postmenopausal women in Ghana.

Hair relaxers and skin lighteners have been commonly used by African women, with suggestions that they may have hormonal activity.
Ashley M Geczik, Roni T Falk, Xia Xu, Beatrice Wiafe-Addai, Joel Yarney, Baffour Awuah, Richard Biritwum, Verna Vanderpuye, Florence Dedey, Ernest Adjei, Francis Aitpillah, Ernest Osei-Bonsu, Joseph Oppong, Nicholas Titiloye, Lawrence Edusei, Kofi Nyarko, Joe-Nat Clegg-Lamptey, Seth Wiafe, Daniel Ansong, Thomas U Ahearn, Jonine Figueroa, Montserrat Garcia-Closas, Louise A Brinton, Britton Trabert

1039 related Products with: Relation of circulating estrogens with hair relaxer and skin lightener use among postmenopausal women in Ghana.



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#34991928   2021/12/30 To Up

Intranasal immunization with a Middle East respiratory syndrome-coronavirus antigen conjugated to the M-cell targeting ligand Co4B enhances antigen-specific mucosal and systemic immunity and protects against infection.

Middle East respiratory syndrome (MERS) is a threat to public health worldwide. A vaccine against the causative agent of MERS, MERS-coronavirus (MERS-CoV), is urgently needed. We previously identified a peptide ligand, Co4B, which can enhance antigen (Ag) delivery to the nasal mucosa and promote Ag-specific mucosal and systemic immune responses following intranasal immunization. MERS-CoV infects via the respiratory route; thus, we conjugated the Co4B ligand to the MERS-CoV spike protein receptor-binding domain (S-RBD), and used this to intranasally immunize C57BL/6 and human dipeptidyl peptidase 4-transgenic (hDPP4-Tg) mice. Ag-specific mucosal immunoglobulin (Ig) A and systemic IgG, together with virus-neutralizing activities, were highly induced in mice immunized with Co4B-conjugated S-RBD (S-RBD-Co4B) compared to those immunized with unconjugated S-RBD. Ag-specific T cell-mediated immunity was also induced in the spleen and lungs of mice intranasally immunized with S-RBD-Co4B. Intranasal immunization of hDPP4-Tg mice with S-RBD-Co4B reduced immune cell infiltration into the tissues of virus-challenged mice. Finally, S-RBD-Co4B-immunized mice exhibited were better protected against infection, more likely to survive, and exhibited less body weight loss. Collectively, our results suggest that S-RBD-Co4B could be used as an intranasal vaccine candidate against MERS-CoV infection.
Ye Lin Yang, Ju Kim, Yongsu Jeong, Yong-Suk Jang

1879 related Products with: Intranasal immunization with a Middle East respiratory syndrome-coronavirus antigen conjugated to the M-cell targeting ligand Co4B enhances antigen-specific mucosal and systemic immunity and protects against infection.

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#34990642   2022/01/04 To Up

Antibody-drug conjugates: Resurgent anticancer agents with multi-targeted therapeutic potential.

Antibody-drug conjugates (ADCs) constitute a relatively new group of anticancer agents, whose first appearance took place about two decades ago, but a renewed interest occurred in recent years, following the success of anti-cancer immunotherapy with monoclonal antibodies. Indeed, an ADC combines the selectivity of a monoclonal antibody with the cell killing properties of a chemotherapeutic agent (payload), joined together through an appropriate linker. The antibody moiety targets a specific cell surface antigen expressed by tumor cells and/or cells of the tumor microenvironment and acts as a carrier that delivers the cytotoxic payload within the tumor mass. Despite advantages in terms of selectivity and potency, the development of ADCs is not devoid of challenges, due to: i) low tumor selectivity when the target antigens are not exclusively expressed by cancer cells; ii) premature release of the cytotoxic drug into the bloodstream as a consequence of linker instability; iii) development of tumor resistance mechanisms to the payload. All these factors may result in lack of efficacy and/or in no safety improvement compared to unconjugated cytotoxic agents. Nevertheless, the development of antibodies engineered to remain inert until activated in the tumor (e.g., antibodies activated proteolytically after internalization or by the acidic conditions of the tumor microenvironment) together with the discovery of innovative targets and cytotoxic or immunomodulatory payloads, have allowed the design of next-generation ADCs that are expected to possess improved therapeutic properties. This review provides an overview of approved ADCs, with related advantages and limitations, and of novel targets exploited by ADCs that are presently under clinical investigation.
Claudia Ceci, Pedro Miguel Lacal, Grazia Graziani

2345 related Products with: Antibody-drug conjugates: Resurgent anticancer agents with multi-targeted therapeutic potential.

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#34986721   // To Up

Pharmaceutical strategies for preventing toxicity and promoting antioxidant and anti-inflammatory actions of bilirubin.

Bilirubin (BR) is the final product of haem catabolism. Disruptions along BR metabolic/transport pathways resulting from inherited disorders can increase plasma BR concentration (hyperbilirubinaemia). Unconjugated hyperbilirubinemia may induce BR accumulation in brain, potentially causing irreversible neurological damage, a condition known as BR encephalopathy or kernicterus, to which newborns are especially vulnerable. Numerous pharmaceutical strategies, mostly based on hemoperfusion, have been proposed over the last decades to identify new valid, low-risk alternatives for BR removal from plasma. On the other hand, accumulating evidence indicates that BR produces health benefits due to its potent antioxidant, anti-inflammatory and immunomodulatory action with a significant potential for the treatment of a multitude of diseases. The present manuscript reviews both such aspects of BR pharmacology, gathering literature data on applied pharmaceutical strategies adopted to: (i) reduce the plasma BR concentration for preventing neurotoxicity; (ii) produce a therapeutic effect based on BR efficacy in the treatment of many disorders.
Alessio Nocentini, Alessandro Bonardi, Simone Pratesi, Paola Gratteri, Carlo Dani, Claudiu T Supuran

1097 related Products with: Pharmaceutical strategies for preventing toxicity and promoting antioxidant and anti-inflammatory actions of bilirubin.

1000 1000 TESTS/0.65ml100.00 ul100ul0.1 mg100ul1 ml200 100μg100 μl1,000 tests

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