- Changshanone derivatives and their pharmaceutical compositions and uses
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The present application relates to a changshanone derivative and a pharmaceutical composition and use thereof, the changshanone derivative is shown in formula I, wherein m is 1 to 4, n is 1 to 10, A is H or a detection marker, such as a biotin marker. The present application further relates to a pharmaceutical composition comprising a derivative of changshanone of formula I and its application in the treatment of cancer. Equation I.
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- Synthesis of Na2S2O4 mediated cleavable affinity tag for labeling of O-GlcNAc modified proteins via azide-alkyne cycloaddition
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A facile and convergent procedure for the synthesis of azobenzene-based probe was reported, which could selectively release interested proteins conducted with sodium dithionite. Besides, the cleavage efficiency is closely associated with the structural features, in which an ortho-hydroxyl substituent is necessary for reactivity. In addition, the azobenzene tag applied in the Ac4GlcNAz-labled proteins demonstrated high efficiency and selectivity in comparison with Biotin-PEG4-Alkyne, which provides a useful platform for enrichment of any desired bioorthogonal proteomics.
- Wang, Jiajia,Dou, Biao,Zheng, Lu,Cao, Wei,Zeng, Xueke,Wen, Yinhang,Ma, Jing,Li, Xia
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supporting information
(2021/07/13)
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- From Inhibition to Degradation: Targeting the Antiapoptotic Protein Myeloid Cell Leukemia 1 (MCL1)
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Protein-protein interactions (PPIs) have emerged as significant targets for therapeutic development, owing to their critical nature in diverse biological processes. An ideal PPI-based target is the protein myeloid cell leukemia 1 (MCL1), a critical prosurvival factor in cancers such as multiple myeloma where MCL1 levels directly correlate to disease progression. Current strategies for halting the antiapoptotic properties of MCL1 revolve around inhibiting its sequestration of proapoptotic factors. Existing inhibitors disrupt endogenous regulatory proteins; however, this strategy actually leads to an increase of MCL1 protein levels. Here, we show the development of hetero-bifunctional small molecules capable of selectively targeting MCL1 using a proteolysis targeting chimera (PROTAC) methodology leading to successful degradation. We have confirmed the involvement of the E3 ligase CUL4A-DDB1 cereblon ubiquitination pathway, making these PROTACs a first step toward a new class of antiapoptotic B-cell lymphoma 2 family protein degraders.
- Papatzimas, James W.,Gorobets, Evgueni,Maity, Ranjan,Muniyat, Mir Ishruna,Maccallum, Justin L.,Neri, Paola,Bahlis, Nizar J.,Derksen, Darren J.
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p. 5522 - 5540
(2019/06/17)
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- INHIBITORS OF BRUTON'S TYROSINE KINASE AND METHODS OF THEIR USE
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The present disclosure is directed to compounds of formula I and methods of their use and preparation, as well as compositions comprising compounds of formula I.
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- POLYCYCLIC EPOXIDES AND COMPOSITIONS THEREOF WITH ANTI-CANCER ACTIVITIES
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The present technology provides polycyclic epoxides of Formula I, compositions comprising such expoxides and methods of using such epoxides. In particular, these compounds are useful for inhibiting cancer cell proliferation and tumor angiogenesis or treating ovarian, breast, prostate, liver, pancreatic, and colon cancers, as well as leukemia.
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- HETEROCYCLIC COMPOUNDS AND USES THEREOF
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The present invention relates to pharmaceutical compounds, compositions and methods, especially as they are related to compositions and methods for the treatment and/or prevention of a proliferation disorder, a cancer, a tumor, an inflammatory disease, an autoimmune disease, psoriasis, dry eye or an immunologically related disease, and in some embodiments diseases or disorders related to the dysregulation of kinase such as, but not limited to, EGFR (including HER), Alk, PDGFR, BLK, BMX/ETK, FLT3(D835Y), ITK, TEC, TXK, BTK, or JAK, and the respective pathways.
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- TRIFUNCTIONAL CROSSLINKING REAGENTS
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The present invention relates to trifunctional crosslinking reagents as defined in claim 1, where HRN is a hydrazine-protecting group selected from hydrazones (R'R"C=NNH2), said hydrazone being aldehyde or ketone hydrazone, said substituents R', R" being selected from hydrogen, substituted (C1-C6)alkyl, substituted aryl and substituted heteroaryl. The invention further provides trifunctional crosslinking reagents suitable for the detection, isolation and purification of captured glycopeptides, their methods of production, as well as their use in methods for detecting, identifying and characterizing interactions between ligands and their corresponding glycoprotein target receptors on living cells and in biological fluids.
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- HIGH AFFINITY DIGOXIGENIN BINDING PROTEINS
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Isolated polypeptides with steroid binding activity and methods for their use as therapeutics and detection agents are disclosed herein.
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Paragraph 0147
(2016/01/21)
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- New affinity-based probes for capturing flavonoid-binding proteins
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Flavonoid-bearing probes have been designed and synthesized to explore their ability to selectively capture target proteins or biosynthetic enzymes under oxidative activation. A proof-of-concept study using biotinylated (epi)catechin-bearing affinity-based probes herein demonstrates the ability of these probes to capture the LDOX flavonoid enzyme using sodium periodate as the oxidant.
- Carrié, Hélène,Tran, Dong Tien,Rousseau, Sabrina,Chaignepain, Stéphane,Schmitter, Jean-Marie,Deffieux, Denis,Quideau, Stéphane
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supporting information
p. 9387 - 9389
(2014/08/05)
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- A quartz crystal microbalance method to study the terminal functionalization of glycosaminoglycans
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We demonstrate the quartz crystal microbalance as a novel method to quantify the reaction yields and stability of the terminal conjugation of chemically complex molecules. Oxime ligation is identified as a facile, broadly applicable method for the reducing-end conjugation of glycosaminoglycans that overcomes the limited stability and yield of popular hydrazone ligation.
- Thakar, Dhruv,Migliorini, Elisa,Coche-Guerente, Liliane,Sadir, Rabia,Lortat-Jacob, Hugues,Boturyn, Didier,Renaudet, Olivier,Labbe, Pierre,Richter, Ralf P.
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p. 15148 - 15151
(2015/01/09)
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- Quantitative detection of 8-oxo-7,8-dihydro-2′-deoxyguanosine using chemical tagging and qPCR
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8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) is a commonly formed DNA lesion that is useful as a biomarker for oxidative stress. Although methods for selective quantification of 8-oxodGuo exist, there is room for additional methods that are sensitive a
- Bajacan, John Ernest Vallarta,Hong, In Seok,Penning, Trevor W.,Greenberg, Marc M.
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p. 1227 - 1235
(2014/08/05)
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- Site-selective azide incorporation into endogenous RNase A via a "chemistry" approach
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Site-selective labeling of endogenous proteins represents a major challenge in chemical biology, mainly due to the absence of unique reactive groups that can be addressed selectively. Recently, we have shown that surface-exposed lysine residues of two end
- Chen, Xi,Henschke, Lars,Wu, Qianzhen,Muthoosamy, Kasturi,Neumann, Boris,Weil, Tanja
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p. 353 - 361
(2013/02/23)
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- PH responsive Janus-like supramolecular fusion proteins for functional protein delivery
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A facile, noncovalent solid-phase immobilization platform is described to assemble Janus-like supramolecular fusion proteins that are responsive to external stimuli. A chemically postmodified transporter protein, DHSA, is fused with (imino)biotinylated cargo proteins via an avidin adaptor with a high degree of spatial control. Notably, the derived heterofusion proteins are able to cross cellular membranes, dissociate at acidic pH due to the iminobiotin linker and preserve the enzymatic activity of the cargo proteins β-galactosidase and the enzymatic subunit of Clostridium botulinum C2 toxin. The mix-and-match strategy described herein opens unique opportunities to access macromolecular architectures of high structural definition and biological activity, thus complementing protein ligation and recombinant protein expression techniques.
- Kuan, Seah Ling,Ng, David Y. W.,Wu, Yuzhou,Foertsch, Christina,Barth, Holger,Doroshenko, Mikheil,Koynov, Kaloian,Meier, Christoph,Weil, Tanja
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p. 17254 - 17257
(2014/01/06)
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- Synthesis of biotinylated episilvestrol: Highly selective targeting of the translation factors eIF4AI/II
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Silvestrol (1) and episilvestrol (2) are protein synthesis inhibitors, and the former has shown efficacy in multiple mouse models of cancer; however, the selectivity of these potent cytotoxic natural products has not been described. Herein, it is demonstr
- Chambers, Jennifer M.,Lindqvist, Lisa M.,Webb, Andrew,Huang, David C. S.,Savage, G. Paul,Rizzacasa, Mark A.
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supporting information
p. 1406 - 1409
(2013/05/08)
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- Synthesis of biotin linkers with the activated triple bond donor [p-(N-propynoylamino)toluic Acid] (PATA) for efficient biotinylation of peptides and oligonucleotides
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Biotin is an important molecule for modern biological studies including, e.g., cellular transport. Its exclusive affinity to fluorescent streptavidin/avidin proteins allows ready and specific detection. As a consequence methods for the attachment of biotin to various biological targets are of high importance, especially when they are very selective and can also proceed in water. One useful method is Hueisgen dipolar [3+2]-cycloaddition, commonly referred to as "click chemistry". As we reported recently, the activated triple bond donor p-(N-propynoylamino)toluic acid (PATA) gives excellent results when used for conjugations at submicromolar concentrations. Thus, we have designed and synthesized two biotin linkers, with different lengths equipped with this activated triple bond donor and we proceeded with biotinylation of oligonucleotides and C-myc peptide both in solution and on solid support with excellent yields of conversion.
- Jezowska, Martina,Romanowska, Joanna,Bestas, Burcu,Tedebark, Ulf,Honcharenko, Malgorzata
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p. 14174 - 14185
(2013/03/14)
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- Nucleic acids targeted to drugs: SELEX against a quadruplex ligand
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A number of small molecules demonstrate selective recognition of G-quadruplexes and are able to stabilize their formation. In this work, we performed the synthesis of two biotin-tagged G4 ligands and analyzed their interactions with DNA by two complementa
- Renaud De La Faverie, Amandine,Hamon, Florian,Di Primo, Carmelo,Largy, Eric,Dausse, Eric,Delaurire, Laurence,Landras-Guetta, Corinne,Toulmé, Jean-Jacques,Teulade-Fichou, Marie-Paule,Mergny, Jean-Louis
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p. 1357 - 1367
(2012/07/01)
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- Efforts toward elucidating Thalidomide's molecular target: An expedient synthesis of the first Thalidomide biotin analogue
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Herein we describe the synthesis of the first Thalidomide-biotin analogue in order to initiate investigations into the unknown molecular mode of action of Thalidomide. In this manner we describe the attachment of biotin tether through the Huisgen 1,3-dipo
- Stewart, Scott G.,Braun, Carlos J.,Polomska, Marta E.,Karimi, Mahdad,Abraham, Lawrence J.,Stubbs, Keith A.
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scheme or table
p. 4059 - 4062
(2010/11/17)
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- Novel hydrazone-based and oxime-based fluorescent and chromophoric/pro-fluorescent and pro-chromophoric reagents and linkers
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Conjugationally extended hydrazine compositions of the formula (RR2)N(H)n(NH2)n, fluorescent hydrazone compositions of the formula (RR2)NN═C(R1R2), methods of the formation of hydrazones from the reaction of conjugationally extended hydrazines with conjugationally extended carbonyls and methods of their use in assays systems are described. Use of these conjugationally extended hydrazine and oxime compositions for direct calorimetric and fluorometric assays wherein a chromophore or the fluorophore is incorporated into the linker that is positioned between a reactive linking moiety and a biotin molecule. More specifically the linker comprises one molecule of a high affinity binding pair such as for example biotin of the biotin/avidin high affinity binding pair, connected to a spacer molecule such as for example a length of polyethyleneglycol followed by a pro-chromophoric, chromophoric, pro-fluorescent or fluorescent moiety connected to an amino-, thiol- or carbohydrate-reactive moiety such as for example succinimidyl, maleimido or aminoxy group respectively, that may covalently link to a biomolecule.
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Page/Page column 11
(2008/12/08)
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- Water soluble multi-biotin-containing compounds
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Water-soluble discrete multi-biotin-containing compounds with at least three (3) biotin moieties are disclosed. The water-soluble biotin-containing compounds may additionally comprise one or more moieties that confer resistance to cleavage by biotinidase or that is cleavable in vitro or in vivo. The discrete multi-biotin-containing compounds may include a reactive moiety that provides a site for reaction with yet another moiety, such as a targeting, diagnostic or therapeutic functional moiety. Biotinylation reagents comprising water-soluble linker moieties are also disclosed and may additionally comprise a biotinidase protective group. Methods for amplifying the number of sites for binding biotin-binding proteins at a selected target using multi-biotin compounds also are disclosed.
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Page/Page column 23
(2010/11/24)
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- Fabrication of chemical microarrays by efficient immobilization of hydrazide-linked substances on epoxide-coated glass surfaces
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(Chemical Equation Presented) Fixed to the spot: A new, efficient, and simple immobilization technique for the construction of chemical microarrays has been developed. This technique is applicable to the site-selective attachment of diverse substances, in
- Lee, Myung-Ryul,Shin, Injae
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p. 2881 - 2884
(2007/10/03)
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- Biotinylated CdSe/ZnSe nanocrystals for specific fluorescent labeling
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A set of two new surface ligands is presented for the preparation of water-soluble, biotinylated CdSe/ZnSe core/shell nanocrystals, suitable for fluorescent biological labeling. It consists of a thiolated diethyleneglycol derivative and an alkylthiol substituted biotin molecule, which replace the initial capping ligands at the nanocrystal surface. Successful ligand exchange and long-term photostability of the modified nanocrystals as well as their highly specific binding to neuronal cells are demonstrated in different labeling experiments.
- Charvet, Nicolas,Reiss, Peter,Roget, Andre,Dapuis, Alain,Gruenwald, Didier,Carayon, Sophie,Chandezon, Frederic,Livache, Thierry
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p. 2638 - 2642
(2007/10/03)
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- Biotin derivatives
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A method for the conditioning of an extracorporeal device is described, as well as a method for extracorporeal extraction of toxic material from mammalian body fluids in connection with diagnosis or treatment of a mammalian condition or disease, in which methods reagents having the ability to extract toxic material from mammalian body fluids are involved, and an extracorporeal device comprising said reagent.
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