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Application of paclitaxel or analogue thereof in inhibition of cilia depolymerization

An analog, paclitaxel technology, applied in the field of medicine, can solve the problem of not being an FDA-certified drug, etc., and achieve the effect of inhibiting the depolymerization of cilia

Pending Publication Date: 2022-04-12
TSINGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, none of the drugs currently found to inhibit ciliary depolymerization is FDA-approved.

Method used

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  • Application of paclitaxel or analogue thereof in inhibition of cilia depolymerization
  • Application of paclitaxel or analogue thereof in inhibition of cilia depolymerization
  • Application of paclitaxel or analogue thereof in inhibition of cilia depolymerization

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] The influence of embodiment 1, paclitaxel or its analogs (docetaxel and cabazitaxel) on cilia depolymerization

[0033] The specific experimental steps of paclitaxel and its analogs (docetaxel and cabazitaxel) on the influence of cilia depolymerization are as follows: get 4 groups of Chlamydomonas cells (algae strain 21gr (mt+; CC-1690) from Chlamydomonas Genetic Center ( University of Minnesota)), the drugs used in the 3 groups of experimental groups were processed with paclitaxel, docetaxel and cabazitaxel respectively, and the control group was processed with 0.5% DMSO, and each drug was treated with four concentrations of 5-50 μM (specifically 5 , 10, 25, 50 μM, the solvent is DMSO) after the cells were treated for 30 min, NaPPi (commercially purchased from Sigma, catalog number MKCG8883) was added to induce depolymerization, samples were taken at corresponding time points, and the lengths of 50 cilia were measured. The culture conditions of Chlamydomonas cells were...

Embodiment 2

[0035] Embodiment 2, analyze paclitaxel or its analog (docetaxel and cabazitaxel) to the cilium influence of normal growth Chlamydomonas cells

[0036] Paclitaxel or its analogs (docetaxel and cabazitaxel) to the cilia of normal growth Chlamydomonas cells affect the specific experimental steps as follows: get 3 groups of Chlamydomonas cells (cell source is the same as Example 1 of the present invention), use 5 Paclitaxel and docetaxel, cabazitaxel and 0.5% DMSO (control) treatment of four concentrations of -50 μ M (being specifically 5, 10, 25, 50 μ M, and the solvent is DMSO) (the cell culture conditions are the same as in Example 1 of the present invention) ) Normal Chlamydomonas cells were sampled at time points of 1, 3, and 5 hours, and the lengths of 50 cilia were measured.

[0037] The above experimental results are as figure 2 as shown, figure 2 The middle abscissa represents the drug treatment time, and the ordinate represents the length of the cilia, and the graph...

Embodiment 3

[0038] Example 3. Analysis of the Effect of Cabazitaxel on Ciliary Depolymerization under Physiological Conditions

[0039] The same amount of positive and negative gametocytes of Chlamydomonas (algae strain 21gr (mt+; CC-1690) and 6145C (mt-; CC-1691) from Chlamydomonas Genetic Center (University of Minnesota)) were mixed and paired, and after 1 hour of pairing ( The pairing rate reaches more than 70%) to obtain zygotic cells. The zygotic cells were divided into two groups, and the zygotic cells were treated with 10 μM drug cabazitaxel and 0.5% DMSO respectively, samples were taken at corresponding time points (2, 3, 3.5, 4 h), and the lengths of 50 cilia were measured.

[0040] The above experimental results are as image 3 as shown, image 3 The middle abscissa represents the drug treatment time, and the ordinate represents the length of the cilia, and the graph shows the mean ± standard deviation. Depend on image 3 It can be seen that the average length of cilia in th...

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Abstract

The invention discloses an application of paclitaxel or an analogue thereof in inhibition of cilia depolymerization. The paclitaxel or the analogue thereof disclosed by the invention is applied to preparation of medicines for treating ciliary diseases. The paclitaxel or the analogue thereof is applied to preparation of the medicine for treating the retinal degeneration. The paclitaxel or the analogues thereof, which are widely applied clinically, have the effects of stabilizing cilia and inhibiting cilia depolymerization, and can be used as a potential medicine for treating cilia diseases caused by cilia degeneration, such as retinopathy caused by retina cilia degeneration.

Description

technical field [0001] The invention relates to the application of paclitaxel or its analogs, in particular to the application of paclitaxel or its analogs in inhibiting cilia depolymerization, and belongs to the technical field of medicine. Background technique [0002] Cilia is a kind of organelle protruding from the cell surface mainly composed of cell microtubules. Cilia exist on almost every cell in human beings. In addition to the function of cell movement, they also have the function of signal perception and transmission. Human vision, hearing, and smell are closely related to cilia. In addition, it also participates in a variety of intracellular signaling pathways, including Hedgehog signaling pathway, Notch signaling pathway, Wnt signaling pathway, mTOR signaling pathway, etc., thereby regulating animal development and physiological homeostasis (Veland et al., Primary cilia and signaling pathways in mammalian development, health and disease. Nephron Physiol 111, p...

Claims

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Application Information

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IPC IPC(8): A61K31/337A61P27/02A61P9/10A61P43/00
Inventor 潘俊敏董志军
Owner TSINGHUA UNIV
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