Application of a brdt protein inhibitor in male antifertility

An anti-fertility, small-molecule inhibitor technology, applied in the field of biomedicine, can solve problems such as low bioavailability, achieve reversible male anti-fertility, reduce drug research costs, and reduce manpower effects.

Active Publication Date: 2018-08-21
国家卫生健康委科学技术研究所
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the anti-fertility effect of JQ1 has good reversibility, it may have the disadvantage of low bioavailability. Therefore, it is still necessary to develop new compounds targeting BRDT. However, there is no research on BRDT inhibitors in my country. Actively develop BRDT inhibitors have important implications

Method used

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  • Application of a brdt protein inhibitor in male antifertility
  • Application of a brdt protein inhibitor in male antifertility
  • Application of a brdt protein inhibitor in male antifertility

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] The construction of embodiment 1 pharmacophore model

[0047] 1. Method

[0048] The three-dimensional structure file of the co-crystal active conformation of human BRDT and JQ1 was downloaded from the PDB database and input to Discovery Studio 3.0 software; the pharmacophore model based on the interaction mode of BRDT and JQ1 complex was constructed by using the pharmacophore building block of Discovery Studio 3.0, Remove water molecules, add hydrogen bonds to form the acceptor structure; set the parameters and conditions, set the parameters of the minimum structural feature and the maximum structural feature to 4 and 6, respectively, the lipophilic site density parameter is set to 15, and the polar site The parameter was set to 20; the active site was identified according to the interaction mode of the acetyl-lysine binding pocket JQ1 and BRDT, and all the action sites were clustered to obtain a pharmacophore model for virtual screening; the final drug was analyzed A...

Embodiment 2

[0051] Example 2 drug class prediction

[0052] 1. Materials

[0053] The compound database of the National New Drug (Microbial) Screening Laboratory of the Institute of Pharmaceutical Biotechnology, Chinese Academy of Medical Sciences and the self-developed microbial natural product database MNPD.

[0054] 2. Method

[0055] Use Lipinski's five rules to screen 80,000 compounds from the compound library to screen out compounds with toxic groups and active groups; conduct water solubility, human intestinal absorption, blood Barrier permeability resistance, cytochrome P4502D6 inhibition, hepatotoxicity, and plasma protein binding rate property prediction, the relative molecular mass is selected to be below 500, the calculated lipid-water partition coefficient CLgP is less than 5, the number of hydrogen bond donors is not more than 5, hydrogen Compounds with no more than 10 bond receptors make the screened compounds have good absorption solubility, non-hepatotoxicity, different...

Embodiment 3

[0058] Embodiment 3 virtual screening based on pharmacophore model

[0059] Input the constructed pharmacophore model as a 3D query structure into the compound database (76984) filtered by Lipinski's five rules and predicted by ADMET for high-throughput virtual screening; retain compounds matching more than half of the pharmacodynamic characteristic elements; finally screen out 270 eligible compounds.

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Abstract

The invention discloses application of a BRDT protein inhibitor in male contraception, and particularly discloses application of a BRDT protein small-molecule inhibitor in male contraception. The invention further discloses a BRDT-targeted method for rationally screening contraception medicine by means of computer-assisted virtual screening.

Description

technical field [0001] The invention relates to the field of biomedicine, more specifically, the invention relates to the application of a BRDT protein inhibitor in male anti-fertility. Background technique [0002] Today, with the development of contraceptive technology so mature, the contraceptive method against male fertility has always been a weak link in the field of reproduction. The currently developed male contraceptives include hormonal and non-hormonal male contraceptives. Hormonal male contraceptives are based on the negative feedback regulation of the hypothalamus-pituitary-testicular axis. The main mechanism is: exogenous testosterone feedback inhibition of luteinizing hormone and follicle stimulation Hormone secretion; reduce the secretion level of testosterone in the testis, inhibit spermatogenesis. There are many candidates for non-hormonal male birth control, and the mechanism of action includes interfering with Sertoli cell function; inhibiting acrosin, bl...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61K31/4184A61P15/16G06F19/00G01N33/68
CPCA61K31/4184A61K45/00G01N33/68G16C20/50
Inventor 王慧萍高娜娜
Owner 国家卫生健康委科学技术研究所
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