101187-40-0Relevant articles and documents
Synthesis and photochemical protein crosslinking studies of hydrophilic naphthalimides
Zhang, Jianxing,Woods, R. Jeremy,Brown, Philip B.,Kap, Duk Lee,Kane, Robert R.
, p. 853 - 856 (2002)
A mixture of 4-alkylamino-1,8-naphthalimides has previously been reported to exhibit potential utility as a photochemical tissue-bonding reagent. In order to determine which constituents of the mixture were responsible for the observed tissue bonding and
Solution- and solid-phase synthesis of components for tethered bilayer membranes
Bendavid,Burns,Field,Hashimoto,Ridley,Sandanayake,Wieczorek
, p. 3709 - 3716 (2001)
The synthesis of the novel compound PhCH2SS(C24H44N4O10) (C20H41) (5) for the preparation of tethered bilayer membranes is described. The compound is the all-amide analogue of the previously reported ester-containing membrane-forming material PhCH2SS(C24H40O14) (C20H41) (1). The advanced intermediate (C20S41) C16H28N3O8 (17) was prepared from the same starting materials using both solution-phase (13% yield) and solid-phase (81% yield) techniques. Monolayers on gold derived from 5 have been analyzed by ellipsometry and FTIR. The monolayers exhibit thicknesses similar to monolayers derived from 1 and possess H-bonded amide functionality.
GM1-Binding Conjugates to Improve Intestinal Permeability
Melkoumov, Alexandre,St-Jean, Isabelle,Banquy, Xavier,Leclair, Grégoire,Leblond Chain, Jeanne
, p. 60 - 70 (2019)
Drugs and proteins with poor intestinal permeability have a limited oral bioavailability. To remediate this problem, a receptor-mediated endocytosis and transcytosis approach was explored. Indeed, the nontoxic β subunit of cholera toxin (CTB) can cross the intestinal barrier by binding to receptor GM1. In this study, we explored the use of GM1-binding peptides and CTB as potential covalent carriers of poorly permeable molecules. GM1-binding peptides (G23, P3) and CTB were conjugated to poorly permeable fluorescent probes such as fluorescein isothiocyanate (FITC) and albumin-FITC using triethylene glycol spacers and click chemistry. The affinity of the peptide conjugates with receptor GM1 was confirmed by isothermal titration calorimetry or microscale thermophoresis, and the results suggested the involvement of nonspecific interactions. Conjugating the model drugs to G23 and P3 improved the internalization into Caco-2 and T84 cells, although the process was not dependent on the amount of GM1 receptor. However, conjugation of bovine serum albumin FITC to CTB increased the internalization in the same cells in a GM1-dependent pathway. Peptide conjugates demonstrated a limited permeability through a Caco-2 monolayer, whereas G23 and CTB conjugates slightly enhanced permeability through a T84 cell monolayer compared to model drugs alone. Since CTB can improve the permeability of large macromolecules such as albumin, it is an interesting carrier for the improvement of oral bioavailability of various other macromolecules such as heparins, proteins, and siRNAs.
Target protein degradation inducing compound, preparation method thereof and pharmaceutical composition for preventing or treating targeted protein related diseases containing the same as an active ingredient
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Paragraph 0943; 0945-0947, (2020/05/01)
The present invention relates to a degraducer for inducing the decomposition of target protein, a producing method thereof, and a pharmaceutical composition for preventing or treating target protein-related diseases by containing the degraducer as an active ingredient. A novel compound represented by chemical formula 1, ULB-L-PTM, by the present invention, as a degraducer compound inducing the decomposition of target protein using cereblon E3 ubiquitin ligase, is able to significantly achieve a target protein degradation-inducing activity with an excellent binding activity of a cereblon E3 ubiquitin ligase binder thereby, being able to achieve an excellent protein degradation activity by targeting protein or polypeptide related to various diseases. The bromodomain-containing pharmaceutical composition for preventing or treating protein-related diseases or conditions contains the novel compound represented by chemical formula 1 as an active ingredient and has a useful effect of providing a health functional food composition for prevention or improvement.(AA) Example 22 (nM, 24h)COPYRIGHT KIPO 2020
Targeted and modular architectural polymers employing bioorthogonal chemistry for quantitative therapeutic delivery
Bell, Craig A.,Blinco, James P.,Ediriweera, Gayathri R.,Fletcher, Nicholas L.,Fuchs, Adrian V.,Houston, Zachary H.,Howard, Christopher B.,Mahler, Stephen M.,Simpson, Joshua D.,Thurecht, Kristofer J.,Van De Walle, Matthias,Venkatachalam, Taracad K.
, p. 3268 - 3280 (2020/04/08)
There remain several key challenges to existing therapeutic systems for cancer therapy, such as quantitatively determining the true, tissue-specific drug release profile in vivo, as well as reducing side-effects for an increased standard of care. Hence, it is crucial to engineer new materials that allow for a better understanding of the in vivo pharmacokinetic/pharmacodynamic behaviours of therapeutics. We have expanded on recent "click-to-release" bioorthogonal pro-drug activation of antibody-drug conjugates (ADCs) to develop a modular and controlled theranostic system for quantitatively assessing site-specific drug activation and deposition from a nanocarrier molecule, by employing defined chemistries. The exploitation of quantitative imaging using positron emission tomography (PET) together with pre-targeted bioorthogonal chemistries in our system provided an effective means to assess in real-time the exact amount of active drug administered at precise sites in the animal; our methodology introduces flexibility in both the targeting and therapeutic components that is specific to nanomedicines and offers unique advantages over other technologies. In this approach, the in vivo click reaction facilitates pro-drug activation as well as provides a quantitative means to investigate the dynamic behaviour of the therapeutic agent.
