Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Small molecule compounds inhibiting PD-1/PD-L1 and their uses

A technology of PD-L1 and PD-1, applied in the field of medicine, can solve the problems of slow progress in the development of small molecule drugs

Active Publication Date: 2021-05-04
CHINA PHARM UNIV
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Compared with the good development status of antibody drugs, the development of small molecule drugs is progressing slowly

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
  • Small molecule compounds inhibiting PD-1/PD-L1 and their uses
  • Small molecule compounds inhibiting PD-1/PD-L1 and their uses
  • Small molecule compounds inhibiting PD-1/PD-L1 and their uses

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] The present invention uses a commercial PD-1 / PD-L1 inhibitor screening kit, which is a high-throughput kit developed based on Homogeneous Time-Resolved Fluorescence (HTRF). Mainly rely on the excited rare earth metal chelate to release energy and transfer to the luminescent group to generate detection signal. In the experiment, Tag1-PD-1 with tag 1 will bind to Tag2-PD-L1 with tag 2, and the chelated Eu 3+ After the Tag1 antibody and the Tag2 antibody with the luminescent group XL665, the antibodies will bind to their respective target proteins. In the absence of blocking agents, PD-1 and PD-L1 bind to each other, and the two fluorescent groups are close to each other. , fluorescence resonance energy transfer occurs, and a part of the energy will be transferred from the fluorescence donor Eu 3+ The group transfers to the fluorescent acceptor XL665 group, and generates fluorescence at 665nm, while the energy that has not been transferred will emit fluorescence at 620nm,...

Embodiment 2

[0040] Example 2 Inhibitory effect of compounds M355-0148, M355-0149, and M355-0152 on mouse melanoma in vivo

[0041] Ⅰ. Cell culture

[0042] B16-F10 cells were cultured in 1640 complete medium (containing 10% FBS), and when the cells were in the logarithmic growth phase and the growth confluence reached 80%-90%, they were trypsinized and passaged.

[0043] Ⅱ. Tumor transplantation experiment of mouse melanoma B16-F10

[0044] (1) Grouping of mice

[0045]A total of 24 mice with basically the same growth status were taken and divided into 4 groups, including the control group, M355-0148, M355-0149, and M355-0152 groups; -0152 is a drug, and the dosage is 20mg / kg, administered by intragastric administration.

[0046] (2) Mice were inoculated with melanoma B16-F10 cells intradermally

[0047] ① Anesthetize the mouse: Invert the EP tube containing the melanoma B16-F10 cells for 6 times and draw up the cell culture medium to 0.4ml;

[0048] ② B16F10 cells were intradermally...

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 the use of a compound or a pharmaceutically acceptable salt, ester or solvate thereof in the preparation of a PD-1 / PD-L1 small molecule inhibitor drug. In the present invention, candidate molecules with potential activity in the compound library are screened out through computer simulation, and homogeneous time-resolved fluorescence technology is used to perform high-throughput screening on the binding of candidate molecules to antagonize PD-1 / PD-L1, and select those with better activity. The compound was subjected to a mouse melanoma B16-F10 tumor transplantation experiment, and it was determined that the compound screened by the present invention has anti-tumor activity.

Description

technical field [0001] The invention relates to the use of a class of compounds or pharmaceutically acceptable salts, esters or solvates thereof in the preparation of PD-1 / PD-L1 inhibitor drugs, which belongs to the field of medicine. Background technique [0002] Programmed cell death protein 1 (programmed cell death protein 1, PD-1) is a type I transmembrane protein that is expressed in T cells and can down-regulate the function of the immune system. It consists of 288 amino acids, including the IgV region of the extracellular segment , the transmembrane segment and the intracellular portion. The intracellular portion of the protein has two key phosphorylation sites on the immunoreceptor tyrosine inhibitory motif and the immunoreceptor tyrosine conversion motif, which play a role in the inhibition of T cell signal transduction by PD-1. played an important role in the process. The natural binding ligands of PD-1 are programmed cell death ligand 1 (programmed death-ligand ...

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
Patent Type & Authority Patents(China)
IPC IPC(8): C07D413/14A61P35/00A61K31/4245A61K31/4439
CPCA61P35/00C07D413/14
Inventor 柳军轩春晓谢小雪江经纬
Owner CHINA PHARM UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com