Methods for identifying chemical Modulators of Ras Superfamily GTPase Activity

John Sondek (Inventor), Rafael Rojas (Inventor)

Research output: Patent

Abstract

The present invention provides a method of identifying a compound having the ability to modulate the guanine nucleotide exchange cycle of a Ras superfamily GTPase, comprising: a) contacting the compound with a guanine nucleotide exchange factor and a GTPase and obtaining a baseline fluorescence measurement; b) contacting the guanine nucleotide exchange factor and the GTPase without the compound and obtaining a baseline fluorescence measurement; c) adding a fluorophore-conjugated GTP to the components of (a) and (b), respectively; d) obtaining fluorescence measurements of the respective components of (c) over time; e) subtracting the respective baseline fluorescence measurements of (a) and (b) from each fluorescence measurement of (d); and f) comparing the resulting fluorescence values of (e), wherein a decrease or increase in the rate of fluorescence change with the compound as compared with the rate of fluorescence change without the compound identifies a compound having the ability to modulate the guanine nucleotide exchange cycle of a Ras superfamily GTPase. Further provided are compounds of the invention and pharmaceutical compositions comprising compounds of the invention useful for the treatment of cancer and neurological disorders.
LanguageEnglish
Patent number7807400
IPCC12Q 1/42 (20060101); C12Q 1/34 (20060101)
StatePublished - 1800

Fingerprint

GTP Phosphohydrolases
Modulators
Fluorescence
Patents and inventions
Guanine Nucleotide Exchange Factors
Guanine Nucleotides
Fluorophores
Guanosine Triphosphate
Chemical analysis
Pharmaceutical Preparations

Cite this

Sondek, J., & Rojas, R. (1800). IPC No. C12Q 1/42 (20060101); C12Q 1/34 (20060101). Methods for identifying chemical Modulators of Ras Superfamily GTPase Activity (Patent No. 7807400.)

Methods for identifying chemical Modulators of Ras Superfamily GTPase Activity. / Sondek, John (Inventor); Rojas, Rafael (Inventor).

IPC No.: C12Q 1/42 (20060101); C12Q 1/34 (20060101). Patent No.: 7807400.

Research output: Patent

Sondek, J & Rojas, R 1800, Methods for identifying chemical Modulators of Ras Superfamily GTPase Activity, Patent No. 7807400, IPC No. C12Q 1/42 (20060101); C12Q 1/34 (20060101).
Sondek J, Rojas R, inventors. Methods for identifying chemical Modulators of Ras Superfamily GTPase Activity. C12Q 1/42 (20060101); C12Q 1/34 (20060101). 1800
Sondek, John (Inventor) ; Rojas, Rafael (Inventor). / Methods for identifying chemical Modulators of Ras Superfamily GTPase Activity. IPC No.: C12Q 1/42 (20060101); C12Q 1/34 (20060101). Patent No.: 7807400.
@misc{4dfc25c2769240baa5a8536125567e43,
title = "Methods for identifying chemical Modulators of Ras Superfamily GTPase Activity",
abstract = "The present invention provides a method of identifying a compound having the ability to modulate the guanine nucleotide exchange cycle of a Ras superfamily GTPase, comprising: a) contacting the compound with a guanine nucleotide exchange factor and a GTPase and obtaining a baseline fluorescence measurement; b) contacting the guanine nucleotide exchange factor and the GTPase without the compound and obtaining a baseline fluorescence measurement; c) adding a fluorophore-conjugated GTP to the components of (a) and (b), respectively; d) obtaining fluorescence measurements of the respective components of (c) over time; e) subtracting the respective baseline fluorescence measurements of (a) and (b) from each fluorescence measurement of (d); and f) comparing the resulting fluorescence values of (e), wherein a decrease or increase in the rate of fluorescence change with the compound as compared with the rate of fluorescence change without the compound identifies a compound having the ability to modulate the guanine nucleotide exchange cycle of a Ras superfamily GTPase. Further provided are compounds of the invention and pharmaceutical compositions comprising compounds of the invention useful for the treatment of cancer and neurological disorders.",
author = "John Sondek and Rafael Rojas",
note = "Status: published applicationnumber: 10/593,503 usclass: 435/21 ; 435/18 applicationnumber: 10/593,503; 7807400; C12Q 1/42 (20060101); C12Q 1/34 (20060101)",
year = "1800",
language = "English",
type = "Patent",

}

TY - PAT

T1 - Methods for identifying chemical Modulators of Ras Superfamily GTPase Activity

AU - Sondek,John

AU - Rojas,Rafael

N1 - Status: published applicationnumber: 10/593,503 usclass: 435/21 ; 435/18 applicationnumber: 10/593,503

PY - 1800

Y1 - 1800

N2 - The present invention provides a method of identifying a compound having the ability to modulate the guanine nucleotide exchange cycle of a Ras superfamily GTPase, comprising: a) contacting the compound with a guanine nucleotide exchange factor and a GTPase and obtaining a baseline fluorescence measurement; b) contacting the guanine nucleotide exchange factor and the GTPase without the compound and obtaining a baseline fluorescence measurement; c) adding a fluorophore-conjugated GTP to the components of (a) and (b), respectively; d) obtaining fluorescence measurements of the respective components of (c) over time; e) subtracting the respective baseline fluorescence measurements of (a) and (b) from each fluorescence measurement of (d); and f) comparing the resulting fluorescence values of (e), wherein a decrease or increase in the rate of fluorescence change with the compound as compared with the rate of fluorescence change without the compound identifies a compound having the ability to modulate the guanine nucleotide exchange cycle of a Ras superfamily GTPase. Further provided are compounds of the invention and pharmaceutical compositions comprising compounds of the invention useful for the treatment of cancer and neurological disorders.

AB - The present invention provides a method of identifying a compound having the ability to modulate the guanine nucleotide exchange cycle of a Ras superfamily GTPase, comprising: a) contacting the compound with a guanine nucleotide exchange factor and a GTPase and obtaining a baseline fluorescence measurement; b) contacting the guanine nucleotide exchange factor and the GTPase without the compound and obtaining a baseline fluorescence measurement; c) adding a fluorophore-conjugated GTP to the components of (a) and (b), respectively; d) obtaining fluorescence measurements of the respective components of (c) over time; e) subtracting the respective baseline fluorescence measurements of (a) and (b) from each fluorescence measurement of (d); and f) comparing the resulting fluorescence values of (e), wherein a decrease or increase in the rate of fluorescence change with the compound as compared with the rate of fluorescence change without the compound identifies a compound having the ability to modulate the guanine nucleotide exchange cycle of a Ras superfamily GTPase. Further provided are compounds of the invention and pharmaceutical compositions comprising compounds of the invention useful for the treatment of cancer and neurological disorders.

M3 - Patent

M1 - 7807400

ER -