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Application of 1-indanone in preparation of medicine for treating or preventing autosomal dominant polycystic kidney disease

An autosomal, dominant genetic technology, applied in the direction of drug combination, pharmaceutical formula, urinary system diseases, etc., can solve the problem of ADPKD lack of therapeutic drugs, etc., and achieve the effect of inhibiting the occurrence of vesicles

Active Publication Date: 2021-01-26
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Currently, the only clinically approved drug for the treatment of ADPKD is angiotensin type II receptor (V 2 R) The blocker tolvaptan exerts its inhibitory effect on vesicles by down-regulating the level of cAMP in the body, but clinical data show that V 2 R antagonists only exert inhibitory effect on collecting duct-derived vesicles, but have no significant effect on proximal tubule-derived vesicles, and tolvaptan has certain liver toxicity
At present, there is still a lack of ideal therapeutic drugs for ADPKD in clinic

Method used

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  • Application of 1-indanone in preparation of medicine for treating or preventing autosomal dominant polycystic kidney disease
  • Application of 1-indanone in preparation of medicine for treating or preventing autosomal dominant polycystic kidney disease
  • Application of 1-indanone in preparation of medicine for treating or preventing autosomal dominant polycystic kidney disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 11

[0028] Example 1 Inhibition of vesicle growth by 1-indanone

[0029] Canine kidney collecting duct cells (Madin-Darby canine kidney cells, MDCK) were cultured in three-dimensional Matrigel (Purecol Collagen, Inamed Biomaterials Fremont Company, Cat. No. 5409) in vitro.

[0030] Culture solution 1 is the three-dimensional matrigel concentration obtained by adding three-dimensional matrigel, HEPES (4-hydroxyethylpiperazineethanesulfonic acid), penicillin and streptomycin to 10×MEM culture solution, and the concentration of three-dimensional matrigel is 2.9mg / ml, and the concentration of HEPES is 10mM, penicillin concentration of 100U / ml, streptomycin concentration of 100μg / ml culture solution, pH is 7.4.

[0031] Culture solution 2 is a culture solution in which FBS concentration is 10% and forskolin concentration is 10 μM obtained by adding FBS and forskolin (FSK, forskolin, Sigma company, product number F6886) to DMEM / F12 culture solution. DMEM / F12 culture solution It is a li...

Embodiment 2

[0040] Example 2 Inhibition of 1-indanone on the growth of mouse embryonic kidney vesicles

[0041] C57BL / 6 mice over 6 weeks old (Experimental Animal Center, Peking University Health Science Center) were mated with males and females in the same cage at a ratio of 1:1, and observed whether the female mice had vaginal plugs in the morning of the second day. The mice have been pregnant for 0.5 days, and the mice without vaginal plugs are divided into cages first, and then closed in the cages at night, and then observed on the second day; the pregnant female mice continue to be fed alone for 13 days, and on the 13th day, the transwell plates for embryonic kidneys (Corning Co. , Cat. No. 3401) culture.

[0042] The 13.5-day-old mouse embryonic kidney was taken and placed in the upper chamber of the transwell, and DMEM culture solution containing 8-Br-cAMP (Sigma Company, product number B-5386) with a final concentration of 100 μM was added to the lower culture well for cultivation...

Embodiment 3

[0047] Embodiment 3 in vivo experiments

[0048] The mice used were obtained as follows: the Pkd1 flox / flox Mating of mice and Ksp-Cre mice to obtain a generation of Pkd1 + / - ; Ksp-Cre mice, Pkd1 + / - ; Male mice and female mice of Ksp-Cre mice were mated to obtain wild-type mice Pkd1 + / + ; Ksp-Cre and Pkd1 flox / flox ; Ksp-Cre mice (kPKD mice). Among them, Pkd1 flox / flox The genetic backgrounds of mice and Ksp-Cre mice are both C57BL / 6 mice, which are recorded in the literature (Wang W, Li F, Sun Y, et al. Aquaporin-1 retards renal cyst development in polycystic kidney disease by inhibition of Wnt signaling .FASEB J. 2015;29(4):1551-1563.). Pkd1 flox / flox The mice are mice obtained by knocking out the Pkd1 gene specifically for the whole kidney in the background of C57BL / 6 mice, so that the mice will develop rapidly progressive ADPKD after birth, and the mice can survive for about 7 years after birth. ~10 days or so, genetic identification was carried out on the first d...

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Abstract

The invention provides the application of 1-indanone in the preparation of medicine for treating or preventing autosomal dominant polycystic kidney disease. The present invention uses the MDCK vesicle model to prove that 1-indanone can inhibit the formation and growth of vesicles, and determines the renal pharmacological activity of 1-indanone through the in vitro embryonic kidney vesicle model, which has a significant effect on the development of vesicles in the kidney. Finally, it was further proved in the polycystic kidney mouse model that 1-indanone also had the effect of inhibiting the occurrence and development of vesicles in vivo. The above-mentioned vesicle inhibitory effects in vitro and in vivo showed a dose-effect relationship.

Description

technical field [0001] The invention provides the application of 1-indanone in the preparation of medicines for treating or preventing autosomal dominant polycystic kidney disease, which belongs to the field of biomedicine. Background technique [0002] Fern (scientific name: Pteridium aquilinum (L.)) is a variant of Pteridaceae (Pteridaceae) fern genus European fern, 1-indanone (1-indanone) is extracted from the dried young leaves of European bracken, which has a variety of Biological activity, including anti-inflammatory, antibacterial, antiviral, treatment of Alzheimer's disease, antitumor, etc. Previous studies have shown that 1-indanone derivatives can act as acetylcholinesterase inhibitors to treat Alzheimer's disease. Moreover, 1-indanone can induce the apoptosis of a variety of drug-resistant tumor cells (such as MCF-7, HL-60, MES-SA), and has shown anticancer effects on a variety of malignant tumors such as colon cancer, breast cancer, leukemia, etc. significant i...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/122A61P13/12
CPCA61K31/122A61P13/12
Inventor 杨宝学周虹李小为
Owner PEKING UNIV
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