Camptothecin-antibody conjugate

A technology of antibody conjugates and camptothecin, which can be used in anti-inflammatory agents, drug combinations, anti-tumor drugs, etc., and can solve the problems of insufficient hydrophilicity of molecules and the reduction of the efficacy of exitecan ADC

Pending Publication Date: 2019-01-01
SICHUAN BAILI PHARM CO LTD +1
View PDF4 Cites 17 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, its drawbacks are obvious. At high DAR, the molecule is not sufficiently hydrophilic, resulting in reduced efficacy of exitecan ADC in vivo

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Camptothecin-antibody conjugate
  • Camptothecin-antibody conjugate
  • Camptothecin-antibody conjugate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0066] Synthesis of compound 1

[0067]

[0068] 6-(maleimido) hexanoic acid succinimide ester (MC-OSu, 30g, 0.097mol) was dissolved in 200ml of dichloromethane, then added propargylamine (5.9g, 0.1mol), DIEA ( 24mL, 0.146mol), the reaction was stirred at room temperature. TLC (PE:EA=1:1) monitoring. After the reaction is complete, filter and collect the filtrate, add 200 mL of purified water to the filtrate, then dissolve it with 1 mol / L hydrochloric acid in water to adjust the pH to 5-6, separate the layers, wash the dichloromethane layer with saturated NaCl until neutral, and store at 40°C Concentrate under reduced pressure to obtain a crude product. The crude product was subjected to silica gel column chromatography (eluent PE / EA=3 / 1~2 / 1~1 / 1) to obtain 7.5 g of pure white solid. LC-MSm / z(ES + ): 249.1(M+H) +

Embodiment 2

[0070] Synthesis of compound 2

[0071]

[0072] Compound 1 (7g, 0.028mol), azide polyethylene glycol carboxyl (N 3 -PEG 8 -COOH, 6.62g, 0.014mol), cuprous iodide (3.37g) were dissolved in 200mL of dichloromethane, DIEA (2.8mL, 0.017mol) was slowly added dropwise at room temperature, and the reaction at room temperature was completed, TLC (DCM:MeOH= 8: 1) Monitor progress. After treatment, filtration, the filtrate was concentrated under reduced pressure to obtain a crude product, which was subjected to silica gel column chromatography (eluent DCM / MeOH=100 / 1-50 / 1-10:1) to obtain 9 g of the product. LC-MS m / z (ES + ): 716.4 (M+H) +

Embodiment 3

[0074] Synthesis of Compound 3

[0075]

[0076] Compound 1 (7g, 0.028mol), azide polyethylene glycol carboxyl (N 3 -PEG 4 -COOH, 4.07g, 0.014mol), cuprous iodide (3.37g) were dissolved in 200mL of dichloromethane, and DIEA (2.8mL, 0.017mol) was slowly added dropwise at room temperature, and the reaction at room temperature was completed, TLC (DCM:MeOH= 8: 1) Monitor progress. After treatment, filtration, the filtrate was concentrated under reduced pressure to obtain a crude product, which was subjected to silica gel column chromatography (eluent DCM / MeOH=100 / 1-50 / 1-10:1) to obtain 7.7 g of the product. LC-MS m / z (ES + ): 539.1(M+H) +

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention discloses a camptothecin-antibody conjugate. The category of ADC (Antibody-Drug Conjugate) drugs can be used for effectively improving the drug load, meanwhile, the above aggregation phenomenon is avoided, drug PK (pharmacokinetics) is improved, and an ideal drug effect is obtained from an in vivo model.

Description

technical field [0001] The present invention relates to the application of camptothecin drug-antibody conjugates to treat tumors or other diseases, in particular to the application of a special hydrophilic exinotecan antibody conjugate to increase the stability of the drug in plasma and reduce aggregation , to improve pharmacokinetics (PK). Background technique [0002] As a new type of targeted drug, antibody-drug conjugate (ADC) generally consists of three parts: antibody or antibody-like ligand, small molecule drug, and a linker that couples the ligand and drug. Antibody-conjugated drugs use the specific recognition of antibodies to antigens to transport drug molecules to the vicinity of target cells and effectively release drug molecules to achieve therapeutic purposes. In August 2011, the US Food and Drug Administration (FDA) approved the new ADC drug Adecteis developed by Seattle Genetics for the treatment of Hodgkin's lymphoma and relapsed degenerative large cell lym...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): A61K47/68A61K31/4745A61P35/00
CPCA61K31/4745A61K47/6817A61P35/00A61K38/07A61K47/54A61K47/65A61K47/68A61P29/00A61P37/02
Inventor 朱义李杰万维李卓识李刚锐
Owner SICHUAN BAILI PHARM CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap