250266-79-6Relevant articles and documents
FILAMENTOUS NANOSTRUCTURES AND THEIR USE FOR TREATMENT OF PULMONARY DISEASE
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Paragraph 0163-0164, (2021/04/30)
The present invention provides supramolecular filament and/or sphere compositions and their use as inhalable drug carriers within aerosols. The invention provides insights into peptide designs and supramolecular stability and its crucial role in the interfacial stability and aerosolization properties of the supramolecular filament and/or sphere compositions. The compositions and their properties show that molecular enrichment at the air-liquid interface during nebulization is the primary factor to deplete the monomeric peptide amphiphiles in solution, accounting for the observed morphological disruption/transitions. Importantly, encapsulation of drugs and dyes within the inventive filament and/or sphere compositions notably stabilize their supramolecular structure during nebulization, and the loaded filaments exhibit a linear release profile from a nebulizer device. The compositions disclosed herein can be used as an effective platform for the inhalation-based treatment of many lung and sinusoidal diseases.
ANTIBODY-DRUG CONJUGATES CONTAINING AN ANTI-MESOTHELIN ANTIBODY AND USES THEREOF
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Paragraph 0138-0139, (2021/12/29)
The present disclosure provides an immunoconjugate includes an antibody comprising an antigen-binding fragment that specifically binds to an epitope in mesothelin, N-glycan binding domain and an N-glycan; a linker linking to the N-glycan; and a payload A and a payload B conjugated to the linker, respectively; wherein the payload A and the payload B are the same or different. A pharmaceutical composition comprises the immunoconjugate and a method for treating cancer are also provided in the disclosure.
Supramolecular Design of Unsymmetric Reverse Bolaamphiphiles for Cell-Sensitive Hydrogel Degradation and Drug Release
Anderson, Caleb F.,Chakroun, Rami W.,Cui, Honggang,Sneider, Alexandra,Wang, Feihu,Wirtz, Denis,Wu, Pei-Hsun
supporting information, p. 4434 - 4442 (2020/02/11)
Self-assembly of peptide-based building units into supramolecular nanostructures creates an important class of biomaterials with robust mechanical properties and improved resistance to premature degradation. Yet, upon aggregation, substrate–enzyme interactions are often compromised because of the limited access of macromolecular proteins to the peptide substrate, leading to either a reduction or loss of responsiveness to biomolecular cues. Reported here is the supramolecular design of unsymmetric reverse bolaamphiphiles (RBA) capable of exposing a matrix metalloproteinase (MMP) substrate on the surface of their filamentous assemblies. Upon addition of MMP-2, these filaments rapidly break into fragments prior to reassembling into spherical micelles. Using 3D cell culture, it is shown that drug release is commensurate with cell density, revealing more effective cell killing when more cancer cells are present. This design platform could serve as a cell-responsive therapeutic depot for local chemotherapy.
Her2 targeted polypeptide drug conjugate as well as a preparation method and application thereof
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Paragraph 0048; 0058-0060, (2020/05/30)
The invention relates to an Her2 targeted polypeptide drug conjugate as well as a preparation method and application thereof. The Her2 targeted polypeptide drug conjugate has a molecular structural formula shown in a formula I, wherein Aaa1 is L or D type Lys or Arg; Aaa2 is L or D type Lys or Arg; X is CH2, NH or O; ROH is a hydrophobic antitumor drug; and n is 1 or 2. The Her2 targeted polypeptide drug conjugate provided by the invention can realize targeted drug delivery, the targeted polypeptide can transport the antitumor drug to specific tumor cells, the drug enters the tumor cells and then exerts the characteristic of specific degradation of disulfide bonds at tumor sites, and the antitumor drug is rapidly released. Compared with conventional joint arms such as 2,2'-dithiodiglycolicacid and 3,3'-dithiodipropionic acid, the Her2 targeted polypeptide drug conjugate provided by the invention has the advantages that an anticancer drug in the form of an original drug molecule can beobtained without further hydrolysis, the drug efficacy is improved, and the toxic and side effects on normal cells are reduced.
COMPOUNDS, COMPOSITIONS, AND METHODS FOR TREATMENT OF DISEASES INVOLVING ACIDIC OR HYPOXIC DISEASED TISSUES
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Page/Page column 93, (2019/07/20)
Compounds for treatment of diseases having acidic or hypoxic diseased tissues and pharmaceutical compositions comprising the compounds, as well as methods for making and using the compounds and compositions.
PBD CONJUGATES FOR TREATING DISEASES
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Page/Page column 132; 133, (2017/11/03)
The present disclosure relates to pyrrolobenzodiazepine (PBD) prodrugs and conjugates thereof. The present disclosure also relates to pharmaceutical compositions of the conjugates described herein, methods of making and methods of using the same.
Molecular design and synthesis of self-assembling camptothecin drug amphiphiles
Cheetham, Andrew G.,Lin, Yi-An,Lin, Ran,Cui, Honggang
, p. 874 - 884 (2017/06/09)
The conjugation of small molecular hydrophobic anticancer drugs onto a short peptide with overall hydrophilicity to create self-assembling drug amphiphiles offers a new prodrug strategy, producing well-defined, discrete nanostructures with a high and quantitative drug loading. Here we show the detailed synthesis procedure and how the molecular structure can influence the synthesis of the self-assembling prodrugs and the physicochemical properties of their assemblies. A series of camptothecin-based drug amphiphiles were synthesized via combined solid- and solution-phase synthetic techniques, and the physicochemical properties of their self-assembled nanostructures were probed using a number of imaging and spectroscopic techniques. We found that the number of incorporated drug molecules strongly influences the rate at which the drug amphiphiles are formed, exerting a steric hindrance toward any additional drugs to be conjugated and necessitating extended reaction time. The choice of peptide sequence was found to affect the solubility of the conjugates and, by extension, the critical aggregation concentration and contour length of the filamentous nanostructures formed. In the design of self-assembling drug amphiphiles, the number of conjugated drug molecules and the choice of peptide sequence have significant effects on the nanostructures formed. These observations may allow the fine-tuning of the physicochemical properties for specific drug delivery applications, ie systemic vs local delivery.
TARGETED CONJUGATES AND PARTICLES AND FORMULATIONS THEREOF
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Paragraph 00602, (2016/01/25)
Particles, including nanoparticles and microparticles, and pharmaceutical formulations thereof, comprising conjugates of an active agent such as a therapeutic, prophylactic, or diagnostic agent attached to a targeting moiety via a linker have been designe
NOVEL LINKERS FOR CONJUGATION OF CELL-BINDING MOLECULES
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Paragraph 0048, (2015/10/28)
Cell binding agent-drug conjugates comprising hydrophilic linkers, and methods of using such linkers and conjugates are provided.
Targeted Conjugates Encapsulated in Particles and Formulations Thereof
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Paragraph 0296-0299, (2014/07/08)
Particles, including nanoparticles and microparticles, and pharmaceutical formulations thereof, containing conjugates of an active agent such as a therapeutic, prophylactic, or diagnostic agent attached to a targeting moiety via a linker have been designed which can provide improved temporospatial delivery of the active agent and/or improved biodistribution. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer or infectious diseases.
