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New uses of Shh signaling pathway inhibitor

A signaling pathway and inhibitor technology, applied in the field of biomedicine, can solve the problem of not inhibiting cell proliferation and so on

Inactive Publication Date: 2016-11-23
CANCER INST & HOSPITAL CHINESE ACADEMY OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Vismodegib inhibits growth, but not cell proliferation, of primary pancreatic xenografts

Method used

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  • New uses of Shh signaling pathway inhibitor
  • New uses of Shh signaling pathway inhibitor
  • New uses of Shh signaling pathway inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Embodiment 1, Vil-Cre:Pkd2 f3 / f3 Construction and identification of mouse models

[0043] Vil-Cre:Pkd2 f3 / f3 The mouse is a mouse model that can conditionally knock out Pkd2 established by using the Cre-loxP system, which can produce a clinical phenotype similar to that of human autosomal dominant polycystic kidney disease (Autosomal Dominant Polycystic Kidney Disease, ADPKD) and die early. For renal failure, it can be used as an animal model of ADPKD. Its construction and identification process is as follows:

[0044] 1. Vil-Cre:Pkd2 f3 / f3 Construction of mouse model

[0045] Pkd2 f3 / f3 The mouse was crossed with the transgenic mouse (B6.SJL-Tg(Vil-cre) 997Gum / J) with Vil-Cre recombinase to obtain the F1 generation (theoretically, 1 / 2 of the offspring's genotype is Vil-Cre :Pkd2 + / f3 ; 1 / 2 offspring are genotyped as Pkd2 + / f3 ); Vil-Cre:Pkd2 in the F1 generation + / f3 Mice (PCR identification for the Cre gene, see below for the specific method, the F1 generatio...

Embodiment 2

[0053] Example 2, the application of Vismodegib in the treatment of autosomal dominant polycystic kidney disease

[0054] In this embodiment, Vil-Cre:Pkd2 f3 / f3 Mice are used as animal models of ADPKD to study and analyze the application of Vismodegib in the treatment of autosomal dominant polycystic kidney disease. details as follows:

[0055] 1. Experimental method

[0056] 1. Experimental grouping and processing

[0057] Vismodegib solution: Dissolve Vismodegib in DMSO to a concentration of 80 mg / mL, then dilute to 2 mg / ml with normal saline.

[0058] Grouping and treatment: Divided into treatment group and control group, 10 Vil-Cre:Pkd2 in each group f3 / f3 mice. From the tenth day after the mice were born, subcutaneous injections were carried out for a week, and then changed into intraperitoneal injections, and the drug was withdrawn every day until the mice were two months old. Vismodegib) dosage administration; control group injects equal volume of normal saline co...

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Abstract

The present invention discloses new uses of a Shh signaling pathway inhibitor. The new uses of the Shh signaling pathway inhibitor specifically comprises applications of the Shh signaling pathway inhibitor in preparation of autosomal domi-nant polycystic kidney disease (ADPKD) treatment product, wherein the Shh signaling pathway inhibitor is specifically Vismodegib. According to the present invention, a Vil-Cre:Pkd2f3 / f3 mouse as an ADPKD animal model, and the results show that with the Shh signaling pathway inhibitor Vismodegib, the renal cyst degree of the Vil-Cre:Pkd2f3 / f3 mouse can be reduced, the kidney weight ration of the Vil-Cre:Pkd2f3 / f3 mouse can be reduced, the contents of creatinine and urea nitrogen in the blood of the Vil-Cre:Pkd2f3 / f3 mouse can be reduced, and the renal fibrosis degree of the Vil-Cre:Pkd2f3 / f3 mouse can be reduced; and the important significance is provided for the analysis of the ADPKD pathogenesis and the research and development of the ADPKD treatment drug.

Description

technical field [0001] The invention belongs to the field of biomedicine and relates to a new application of a Shh (sonic hedgehog) signal pathway inhibitor, in particular to the application of an Shh signal pathway inhibitor—Vismodegib in the treatment of autosomal dominant hereditary polycystic kidney disease. Background technique [0002] Vismodegib is a new oral drug with selective Hedgehog signaling pathway inhibition, which has been approved by the FDA for the treatment of basal cell carcinoma. [0003] Vismodegib effectively inhibits the hedgehog pathway and is a novel and specific synthetic small molecule inhibitor with IC50 of 3nM. Vismodegib acts on the Hedgehog signaling pathway, blocking the Hedgehog ligands, that is, the activity of cell surface receptors PTCH and SMO, thereby blocking the Hedgehog signaling pathway. In terms of tissue growth and repair, the Hedgehog signaling pathway is of great significance. Abnormal activation of Hedgehog pathway signaling ...

Claims

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Application Information

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IPC IPC(8): A61K31/4418A61P13/12
Inventor 吴冠青李奥
Owner CANCER INST & HOSPITAL CHINESE ACADEMY OF MEDICAL SCI
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