1639351-92-0Relevant articles and documents
Novel N-Methylated Cyclodepsipeptide Prodrugs for Targeted Cancer Therapy
Wu, Chunlei,Cheng, Zhehong,Lu, Danyi,Liu, Ke,Cheng, Yulian,Wang, Pengxin,Zhou, Yimin,Li, Meiqing,Shao, Ximing,Li, Hongchang,Su, Wu,Fang, Lijing
, p. 991 - 1000 (2021/02/03)
Coibamide A (1) is a highly N-methylated cyclodepsipeptide with low nanomolar antiproliferative activities against various cancer cell lines. In previous work, we discovered a simplified analogue, [MeAla3-MeAla6]-coibamide (1a), which exhibited the same inhibitory abilities as coibamide A. Herein, to reduce the whole-body toxicity and improve the solubility of 1a, two novel peptide-drug conjugates RGD-SS-CA (2) and RGD-VC-CA (3) were designed, synthesized, and evaluated. Composed of cyclodepsipeptide 1a, a tumor-homing RGD motif, and a conditionally labile linker, the conjugates are expected to release 1a tracelessly in specific tumor microenvironments. Compared with RGD-VC-CA (3), RGD-SS-CA (2) proved to be superior in in vitro drug release and cytotoxicity tests. Notably, intravenous injection of RGD-SS-CA (2) into mice-bearing human tumor xenografts induced significant tumor growth suppression with negligible toxicity. Therefore, as a novel prodrug of the coibamide A analogue, conjugate 2 has great potential for further exploration in cancer drug discovery.
NEODEGRADER CONJUGATES
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Paragraph 0539-0540, (2021/10/11)
The present disclosure provides neoDegraders and neoDegraders conjugated to binding moieties. Also provided are compositions comprising the conjugates. The compounds and compositions are useful for treating a disease or condition, e.g., cancer, in a subject in need thereof.
PROTEIN-ANTIVIRAL COMPOUND CONJUGATES
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Paragraph 00181; 00197-00198, (2021/07/31)
Provided herein are compounds, compositions, and methods for the treatment of diseases and disorders associated with influenza, including VX-787 and derivatives thereof, baloxavir and derivatives thereof, and baloxavir marboxil and derivatives thereof, and protein (e.g., antibody) drug conjugates thereof.
COMPOUNDS, COMPOSITIONS, METHODS, AND USES FOR TREATING CANCER AND IMMUNOLOGICAL DISORDERS
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, (2020/02/06)
The present disclosure provides novel polypeptide-therapeutic compound or hormone-therapeutic compound conjugates using cleavable or non-cleavable linkers, whereby the polypeptide or hormone serves to target specific cells using receptor expression on the targeted cell to bind the ligand (polypeptide or hormone) carrying the therapeutic compound unlike antibody drug conjugates. Upon binding, the ligand and the therapeutic compound (multiples of the therapeutic compound in some embodiments) enter the cell by receptor-mediated endocytosis, and release drugs conjugated to the ligand by linkers, to interact with intracellular components to enhance, restore, or block a signal transduction process. The ligands for the polypeptide-therapeutic compound or hormone-therapeutic compound conjugates include, but are not limited to: cytokines, growth factors and hormones among other proteins with corresponding cell surface specific receptors. The disorders targeted by such polypeptide-therapeutic compound or hormone-therapeutic compound conjugates include, but are not limited to: immunological disorders (e.g., allergy and autoimmune disorders) and cancer.
RIFAMYCIN ANALOGS AND ANTIBODY-DRUG CONJUGATES THEREOF
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, (2020/07/14)
The disclosure relates to rifamycin analog compounds, intermediates and precursors thereof, and pharmaceutical compositions capable of inhibiting bacterial growth (e.g., S. aureus growth) and treating bacterial infections (e.g., S. aureus infections). The disclosure further relates to antibody-drug conjugates of rifamycin analog compounds and antibodies, for example, antibodies specific for infectious disease-related targets such as membrane glycoprotein receptor (MSR1), wall teichoic acids (WTA) or Protein A, and methods of use thereof to inhibit bacterial growth and treat bacterial infections.
ANTI-MSR1 ANTIBODIES AND METHODS OF USE THEREOF
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, (2019/11/28)
Provided herein are antibodies and antigen-binding fragments that bind MSR1 and methods of use thereof. According to certain embodiments, the antibodies bind human MSR1 with high affinity. In certain embodiments, the antibodies bind MSR1 without blocking, or blocking less than 90%, of modified LDL binding to MSR1. In some embodiments, the antibodies bind cell surface expressed-MSR1 and are internalized. The antibodies of the invention may be fully human antibodies. The invention includes anti-MSR1 antibodies, or antigen-binding fragments thereof, conjugated to drugs or therapeutic compounds.
A kind of targeting scar-free release drug conjugates and its preparation method and application (by machine translation)
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Paragraph 0060-0063, (2019/07/04)
The invention relates to a kind of targeting scar-free release drug conjugates and its preparation method and application. Specific claims a targeting scar-free release drug conjugates, the structure thereof is T - L - D, on behalf of the targeting group T, L on behalf of the joint, on behalf of the active ingredient D, wherein T is selected from the RGD peptide, RGD peptide ring, RGD peptide derivatives, RGD peptide derivatives, folic acid, cell-penetrating peptide, nucleic acid aptamer, fluorescent dye; D having tertiary medicament active ingredient, preferably [...] A, [...] A derivatives; L is A - BC - E, BC representative enzyme restriction site. The invention use with target function, easy to synthesize a modified ring RGD to replace an expensive, is not easy to synthetic antibody is used as a targeting molecule, preparation is more simple, also reach very high specific targeting, the specificity of the enzyme at the same time under the action of cutting, by the ammonium salt of the amino phenmethyl season self-eliminating, realize seamless release pharmaceutical active ingredient. (by machine translation)
Highly Efficient Synthesis of a Staphylococcus aureus Targeting Payload to Enable the First Antibody–Antibiotic Conjugate
Linghu, Xin,Segraves, Nathaniel L.,Abramovich, Ifat,Wong, Nicholas,Müller, Barbara,Neubauer, Nadja,Fantasia, Serena,Rieth, Sebastian,Bachmann, Stephan,Jansen, Michael,Sowell, C. Gregory,Askin, David,Koenig, Stefan G.,Gosselin, Francis
supporting information, p. 2837 - 2840 (2018/03/01)
A practical synthesis of the complex payload for an anti-Staphylococcus aureus THIOMABTM antibody–antibiotic conjugate (TAC) is described. The route takes advantage of a delicate oxidative condensation, achieved using a semi-continuous flow procedure. It allows for the generation of kilogram quantities of a key intermediate to enable a mild nucleophilic aromatic substitution to the tertiary amine free drug. The linker component is introduced as a benzylic chloride, which allows formation of the quaternary ammonium salt linker-drug. This chemical process surmounts numerous synthetic challenges and navigates deeply colored and unstable compounds to support clinical studies to counter S. aureus bacterial infections.
PROCESS FOR THE PREPARATION OF AN ANTIBODY-RIFAMYCIN CONJUGATE
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Page/Page column 24; 25, (2017/09/15)
Processes are described for the preparation of F-benzoxazinorifamycin I: and intermediates for conjugation with an antibody.
ANTI-WALL TEICHOIC ANTIBODIES AND CONJUGATES
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Paragraph 0386, (2016/01/15)
The invention provides anti-wall teichoic acid antibodies and antibiotic conjugates thereof, and methods of using the same.