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Pyrimidylaminobenzamide Derivatives For the Treatment of Neurofibromatosis

Inactive Publication Date: 2008-12-25
MANLEY PAUL W
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

A tumor that grows on the nerve to the eye is called an optic glioma, and if it grows large enough can cause problems with vision, including blindness.
If untreated, a neurofibroma can cause severe nerve damage leading to loss of function to the area stimulated by that nerve, such as malformation of the long bones, curvature of the spine, short stature and growth hormone deficiency.
Tumors on the optic nerve can cause visual loss, on the gastrointestinal tract may cause bleeding or obstruction, on the brain may lead to learning difficulties (speech problems), behavioural problems (learning disabilities or mental retardation), hearing problems, increased risk of epilepsy.

Method used

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  • Pyrimidylaminobenzamide Derivatives For the Treatment of Neurofibromatosis
  • Pyrimidylaminobenzamide Derivatives For the Treatment of Neurofibromatosis
  • Pyrimidylaminobenzamide Derivatives For the Treatment of Neurofibromatosis

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[0067]The human KIT gene encoding aa 544-976 ws cloned into the baculovirus donor plasmid pFB-GST-01. This coding sequence was excised using restriction endonucleases Bam H1 and EcoR1 and ligated to a Bac to Bac donor vector pFB-GEX-P1 with compatible ends. Subsequently the desired mutations were brought into the KIT gene (by Dr. M Heinrich). Due to a frame shift within the original plasmid that was used to generate the mutant coding sequences, the mutated plasmid inserts were excised and inserted into the Bac-to-Bac donor vector pFB-GST-01 using the restriction enzymes BamH1-EcoR1 for each mutant. Automated sequencing confirmed the correct sequence to be present for each mutant plasmid.

[0068]Bacmid DNA was generated from 10 colonies each of DH10Bac cells transformed with pFB-G01-KIT-mutant plasmid clones as described in materials and methods and these transfected into Sf9 cells. The transfected cells were pelleted and the resultant recombinant baculovirus present in the supernatant...

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Abstract

The present invention relates to the use of pyrimidylaminobenzamide derivatives for the preparation of a drug for the treatment of non-cancerous, benign brain tumors, especially for the curative and / or prophylactic treatment of NF, and to a method of treating non-cancerous, benign brain tumors, especially for the curative and / or prophylactic treatment of NF.

Description

SUMMARY OF THE INVENTION[0001]The present invention relates to the use of pyrimidylaminobenzamide derivatives for the treatment of, and preparation of a drug for the treatment of, non-cancerous, benign brain tumors, especially for the curative and / or prophylactic treatment of meningiomas, schwannomas, craniopharyngiomas, dermoids, epidermoids, hemangioblastomas, choroid plexus papillomas and pineal region tumors; especially those tumors associated with neurofibromatosis types 1 and 2, and tumors occurring along the skull base.BACKGROUND OF THE INVENTION[0002]Neurofibromatosis (NF) is a genetic disorder that affects the bone, soft tissue, skin and nervous system. It is classified into neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2), occurring in about 1 in 3,000 and 1 in 50,000 births, respectively. The disorders occur as a result of genetic defects, with NF1 resulting from a mutation on a gene located on chromosome 17 and NF2 on chromosome 22.[0003]NF1, also known ...

Claims

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Application Information

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IPC IPC(8): A61K31/506A61P35/00
CPCA61K31/506A61K45/06C07D401/14A61K2300/00A61P25/00A61P35/00A61P35/02A61P43/00
Inventor MANLEY, PAUL W.
Owner MANLEY PAUL W
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