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Compositions and methods for treating cancer

A compound and an independent technology, applied in biochemical equipment and methods, chemical equipment and methods, translation products of oncogenes, etc., can solve the problems of reducing GTPase activity, reducing Ras sensitivity, increasing active GTP-binding populations, etc.

Pending Publication Date: 2019-09-27
RGT UNIV OF CALIFORNIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Most of these mutations have been shown to reduce the sensitivity of Ras to GAP stimulation and reduce its intrinsic GTPase activity, leading to an increase in the active GTP-bound population

Method used

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  • Compositions and methods for treating cancer
  • Compositions and methods for treating cancer
  • Compositions and methods for treating cancer

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0168]Preparation and screening of combinatorial chemical libraries is well known to those skilled in the art. Such combinatorial chemical libraries include, but are not limited to, peptide libraries (see, e.g., U.S. Patent 5,010,175, Furka, Int. J. Pept. Prot. Res. 37:487-493 (1991) and Houghton et al., Nature 354:84-88 (1991)). Other chemistries for generating chemical diversity libraries can also be used. Such chemicals include, but are not limited to: peptoids (e.g., PCT Publication No. WO 91 / 19735), encoded peptides (e.g., PCT Publication WO 93 / 20242), random biooligomers (e.g., PCT Publication No. WO 92 / 00091), benzodiazepines (e.g., U.S. Patent No. 5,288,514), diversomers such as hydantoins, benzodiazepines, and dipeptides (Hobbs et al., U.S. National Proc. of the Academy of Sciences (Proc.Nat.Acad.Sci.USA)" 90:6909-6913 (1993)), alkene polypeptide (Hagihara et al., "J.Amer.Chem.Soc.)" 114 :6568(1992)), non-peptidic peptide mimetics with glucose backbone (Hirschmann ...

Embodiment P1

[0616] Embodiment P1. A compound having the formula:

[0617] in,

[0618] R 1 are independently halogen, -CX 1 3 , -CHX 1 2 、-CH 2 x 1 ,-OCX 1 3 、-OCH 2 x 1 , -OCHX 1 2 , -CN, -SO n1 R 1D 、-SO v1 NR 1A R 1B , -NHC(O)NR 1A R 1B , -N(O) m1 , -NR 1A R 1B , -C(O)R 1C , -C(O)-OR 1C , -C(O)NR 1A R 1B , -OR 1D , -NR 1A SO 2 R 1D , -NR 1A C(O)R 1C , -NR 1A C(O)OR 1C , -NR 1A OR 1C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted substituted aryl or substituted or unsubstituted heteroaryl;

[0619] R 2 are independently halogen, -CX 2 3 , -CHX 2 2 、-CH 2 x 2 ,-OCX 2 3 、-OCH 2 x 2 , -OCHX 2 2 , -CN, -SO n2 R 2D 、-SO v2 NR 2A R 2B , -NHC(O)NR 2A R 2B , -N(O) m2 , -NR 2A R 2B , -C(O)R 2C , -C(O)-OR 2C , -C(O)NR 2A R 2B , -OR 2D , -NR 2A SO 2 R 2D , -NR 2A C(O)R 2C , -NR...

Embodiment P2

[0640] Embodiment P2. The compound of embodiment P1, wherein E is a covalent cysteine ​​modification moiety.

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PUM

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Abstract

Disclosed herein, inter alia, are compositions and methods for modulating Ras and treating cancer.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of US Provisional Application No. 62 / 434,971, filed December 15, 2016, which is hereby incorporated by reference in its entirety and for all purposes. [0003] Statement of Rights Concerning Inventions Made Under Federally Sponsored Research and Development [0004] This invention was made with government support under R01CA190408 awarded by the National Institutes of Health. The government has certain rights in this invention. [0005] References to appendices to "sequence listings," tables, or computer program listings filed as ASCII files [0006] The written sequence listing in file 048536-595001WO Sequence Listing_ST25.txt, created on December 15, 2017, 23,487 bytes, machine format IBM-PC, MS Windows operating system, is incorporated herein by reference. Background technique [0007] Ras proteins are small guanine nucleotide-binding proteins that act as molecular switches by c...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D409/04C12N9/14
CPCC07D231/14C07K14/82A61P35/00C12Y306/05002G01N2333/82G01N33/574G01N2500/04G01N33/68C12N9/14A61K31/415C12N9/96
Inventor K·M·邵克特D·真蒂莱S·摩斯
Owner RGT UNIV OF CALIFORNIA