{"id":2287,"date":"2020-02-24T14:15:05","date_gmt":"2020-02-24T05:15:05","guid":{"rendered":"https:\/\/plaza.umin.ac.jp\/~OIO\/?p=2287"},"modified":"2020-02-24T14:15:05","modified_gmt":"2020-02-24T05:15:05","slug":"kras-g12c%e3%80%80%e3%83%9f%e3%83%a5%e3%83%bc%e3%82%bf%e3%83%b3%e3%83%88%e5%88%86%e5%ad%90%e3%81%a8%e9%98%bb%e5%ae%b3%e8%96%ac%e3%81%ae%e6%a7%8b%e9%80%a0","status":"publish","type":"post","link":"https:\/\/plaza.umin.ac.jp\/~OIO\/?p=2287","title":{"rendered":"KRAS.G12C\u3000\u30df\u30e5\u30fc\u30bf\u30f3\u30c8\u5206\u5b50\u3068\u963b\u5bb3\u85ac\u306e\u69cb\u9020"},"content":{"rendered":"

\u306f\u3058\u3081\u306b<\/h1>\n

KRAS\u306f\u60aa\u6027\u75be\u60a3\u3067\u3057\u3070\u3057\u3070\u5909\u7570\u3059\u308b\u304c\u3093\u907a\u4f1d\u5b50\u3067\u3001\u816b\u760d\u3067\u306e\u30b7\u30b0\u30ca\u30eb\u4f1d\u9054\u5206\u5b50\u3092\u30b3\u30fc\u30c9\u3057\u307e\u3059\u3002\u305d\u306e\u5909\u7570\u5206\u5b50\u306f\u4ee5\u524d\u3088\u308a\u5831\u544a\u3055\u308c\u3066\u3044\u307e\u3057\u305f\u3057\u3001\u963b\u5bb3\u85ac\u306e\u958b\u767a\u304c\u8a66\u307f\u3089\u308c\u3066\u3044\u307e\u3057\u305f\u304c\u306a\u304b\u306a\u304b\u3046\u307e\u304f\u3044\u304b\u306a\u304b\u3063\u305f\u3068\u3044\u3046\u4e8b\u3067\u3001Undruggable KRAS\u3068\u3082\u547c\u3070\u308c\u3066\u3044\u307e\u3057\u305f\u3002\u5148\u65e5\u306e\u98f2\u307f\u4f1a\u3067\u3001\u3068\u3042\u308b\u5148\u751f\u304c\u3001\u3053\u306eKRAS\u5206\u5b50\u5909\u7570\u3067\u3042\u308bG12C\uff0812\u756a\u76ee\u306eGly\u304cCys\u306b\u5909\u308f\u308b\u5909\u7570\uff09\u306b\u5bfe\u3059\u308b\u963b\u5bb3\u85ac\u304c\u6709\u671b\u305d\u3046\u3060\u3068\u3044\u3046\u3088\u3046\u306a\u8a71\u3092\u3055\u308c\u3066\u3044\u307e\u3057\u305f\u3002\u9154\u3063\u3066\u3044\u305f\u306e\u3067\u8a73\u3057\u3044\u3053\u3068\u306f\u899a\u3048\u3066\u3044\u307e\u305b\u3093\u304c\u3001\u3068\u308a\u3042\u3048\u305a\u8abf\u3079\u3066\u307f\u308b\u3068Amgen\u793e\u304b\u3089\u6709\u671b\u305d\u3046\u306a\u963b\u5bb3\u85acAMG510\u304c\u81e8\u5e8a\u958b\u767a\u306b<\/a>\u9032\u3093\u3067\u3044\u308b\u3068\u3044\u3046\u3088\u3046\u306a\u3053\u3068\u304c\u89e3\u308a\u307e\u3057\u305f\u30021<\/sup><\/span><\/p>\n

\u3053\u306e\u963b\u5bb3\u85ac\u306e\u8208\u5473\u6df1\u3044\u70b9\u306f\u3001\u5909\u7570\u3059\u308b\u3053\u3068\u3067Cys\u30a2\u30df\u30ce\u9178\u6b8b\u57fa\u304c\u3067\u304d\u308b\u305f\u3081\u3001\u3053\u306e\u6027\u8cea\u3092\u5229\u7528\u3057\u3066S-S\u30b8\u30b9\u30eb\u30d5\u30a3\u30c9\u7d50\u5408\u3092\u3082\u305f\u3089\u3059\u3088\u3046\u306a\u6700\u9069\u5316\u304c\u306a\u3055\u308c\u3066\u3044\u308b\u4e8b\u3067\u3059\u3002\u3069\u3046\u3044\u3046\u4e8b\u304b\u3068\u3044\u3046\u3068\u3001\u4ed6\u306eATP\u306b\u4f3c\u305f\u5206\u5b50\u304c\u6c34\u7d20\u7d50\u5408\u3067\u306e\u7de9\u3044\u7d50\u5408\u3092\u8907\u6570\u5f62\u6210\u3057\u3066\u7d50\u5408\u90e8\u4f4d\u306b\u56fa\u5b9a\u3055\u308c\u3066\u3044\u308b\u306e\u306b\u5bfe\u3057\u3066\u3001\u30b8\u30b9\u30eb\u30d5\u30a3\u30c9\u7d50\u5408\u3068\u3044\u3046\u5171\u6709\u7d50\u5408\u3067\u7d50\u5408\u90e8\u4f4d\u306b\u7d50\u5408\u3055\u308c\u3066\u3044\u307e\u3059\u3002\u5171\u6709\u7d50\u5408\u306f\u6c34\u7d20\u7d50\u5408\u3088\u308a\u5f37\u3044\uff08\u5916\u3059\u306e\u306b\u5927\u304d\u306a\u30a8\u30cd\u30eb\u30ae\u30fc\u304c\u5fc5\u8981\uff09\u3067\u3059\u306e\u3067\u3001\u6c34\u7d20\u7d50\u5408\u3092\u5229\u7528\u3057\u305f\u963b\u5bb3\u85ac\u3088\u308a\u5f37\u529b\u306a\u963b\u5bb3\u4f5c\u7528\u304c\u671f\u5f85\u3067\u304d\u305d\u3046\u3067\u3059\u3002\u305d\u308c\u304c\u3001\u5909\u7570\u5206\u5b50\u306b\u7279\u7570\u7684\u306b\u4f5c\u7528\u3059\u308b\u3068\u3044\u3046\u70b9\u304c\u5473\u564c\u3067\u3059\u3002<\/p>\n

\u307e\u305f\u3001\u30a2\u30ed\u30b9\u30c6\u30ea\u30c3\u30af\u9175\u7d20<\/a>\u3068\u3044\u3046\u4e8b\u3067\u963b\u5bb3\u85ac\u304c\u7d50\u5408\u3059\u308b\u3068\u3001\u5206\u5b50\u5168\u4f53\u306e\u69cb\u9020\u304c\u5927\u304d\u304f\u5f71\u97ff\u3092\u53d7\u3051\u308b\u3088\u3046\u3067\u3059\u3002\u3068\u3044\u3046\u3053\u3068\u3067\u3001\u305d\u306e\u5909\u5316\u3092\u3068\u308a\u3042\u3048\u305a\u898b\u3066\u307f\u307e\u3059\u3002<\/p>\n

\u65b9\u6cd5<\/h1>\n

\u3060\u3044\u305f\u3044\u524d\u51fa\u306e\u8a18\u4e8b<\/a>\u3068\u540c\u3058\u65b9\u6cd5\u3067\u30e2\u30c7\u30eb\u3092\u4f5c\u6210\u3057\u307e\u3057\u305f\u3002\u5143\u306b\u306a\u308b\u69cb\u9020\u306f\u6b21\u306e\u3082\u306e\u3067\u3001P68X\u306b\u306f\u963b\u5bb3\u85ac\u304c12\u756a\u76ee\u306e\u30b7\u30b9\u30c6\u30a4\u30f3\u306b\u5171\u6709\u7d50\u5408\u3057\u3066\u3044\u307e\u3057\u305f\u3002\u307e\u305f\u3001\u91ce\u751f\u578b\u306e\u69cb\u9020\u3067\u306f1\u756a\u76ee\u304cMet\uff08\u5408\u6210\u306e\u969b\u306e\u7ffb\u8a33\u958b\u59cb\u30b3\u30c9\u30f3\u304cATG\u306a\u306e\u3067Met\u306b\u306a\u3063\u3066\u3057\u307e\u3046\u304c\u6210\u719f\u30bf\u30f3\u30d1\u30af\u3067\u306f\u306a\u304f\u306a\u308b\u3053\u3068\u304c\u591a\u3044\uff09\u306b\u306a\u3063\u3066\u3044\u305f\u306e\u3067\u3001\u554f\u984c\u306eG12C\u306e\u5834\u6240\u306f13\u756a\u76ee\u30681\u500b\u5206\u30ca\u30f3\u30d0\u30fc\u304c\u305a\u308c\u3066\u307e\u3057\u305f\u3002<\/p>\n

1. \u91ce\u751f\u578b\u30d2\u30c8KRAS \uff1aPDB\u3000\u30a8\u30f3\u30c8\u30ea\u30005O2S2<\/sup><\/span><\/p>\n

2. \u5909\u7570KRAS.G12C: PDB \u30a8\u30f3\u30c8\u30ea\u30006P8X3<\/sup><\/span><\/p>\n

\u7d50\u679c<\/h1>\n

\u91ce\u751f\u578b<\/p>\n

\"wild-type\"<\/a><\/p>\n

G12C<\/p>\n

\"G12C\"<\/a><\/p>\n

\u4e0a\u8a18\u3092\u91cd\u306d\u3042\u308f\u305b\u305f\u7269<\/p>\n

\"full\"<\/a><\/p>\n

slab\u30e2\u30fc\u30c9\u3067\u91ce\u751f\u578b<\/p>\n

\"wild-type_slab\"<\/a><\/p>\n

slab\u30e2\u30fc\u30c9\u3067\u5909\u7570\u578b<\/p>\n

\"G12C_slab\"<\/a><\/p>\n

slab\u30e2\u30fc\u30c9\u3067\u91cd\u306d\u3042\u308f\u305b\u305f\u7269<\/p>\n

\"slab\"<\/a><\/p>\n

References<\/h1>\n
\n
\n
\n
\n
1.<\/div>\n
AMG 510 First to Inhibit \u201cUndruggable\u201d KRAS. Cancer Discov<\/i>. 2019;9(8):988-989. [PubMed<\/a>]<\/span><\/div>\n<\/div>\n<\/div>\n
\n
\n
2.<\/div>\n
Guillard S, Kolasinska-Zwierz P, Debreczeni J, et al. Structural and functional characterization of a DARPin which inhibits Ras nucleotide exchange. Nat Commun<\/i>. 2017;8:16111. [PubMed<\/a>]<\/span><\/div>\n<\/div>\n<\/div>\n
\n
\n
3.<\/div>\n
Shin Y, Jeong J, Wurz R, et al. Discovery of <i>N<\/i>-(1-Acryloylazetidin-3-yl)-2-(1<i>H<\/i>-indol-1-yl)acetamides as Covalent Inhibitors of KRAS<sup>G12C<\/sup>. ACS Med Chem Lett<\/i>. 2019;10(9):1302-1308. [PubMed<\/a>]<\/span><\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

\u306f\u3058\u3081\u306b KRAS\u306f\u60aa\u6027\u75be\u60a3\u3067\u3057\u3070\u3057\u3070\u5909\u7570\u3059\u308b\u304c\u3093\u907a\u4f1d\u5b50\u3067\u3001\u816b\u760d\u3067\u306e\u30b7\u30b0\u30ca\u30eb\u4f1d\u9054\u5206\u5b50\u3092\u30b3\u30fc\u30c9\u3057\u307e\u3059\u3002\u305d\u306e\u5909\u7570\u5206\u5b50\u306f\u4ee5\u524d\u3088\u308a\u5831\u544a\u3055\u308c\u3066\u3044\u307e\u3057\u305f\u3057\u3001\u963b\u5bb3\u85ac\u306e\u958b\u767a\u304c\u8a66\u307f\u3089\u308c\u3066\u3044\u307e\u3057\u305f\u304c\u306a\u304b\u306a\u304b\u3046\u307e\u304f\u3044\u304b\u306a\u304b\u3063\u305f\u3068\u3044\u3046\u4e8b\u3067\u3001Un…<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[5],"tags":[],"class_list":["post-2287","post","type-post","status-publish","format-standard","hentry","category-miscellaneous"],"jetpack_featured_media_url":"","jetpack_shortlink":"https:\/\/wp.me\/p9b6zl-AT","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/plaza.umin.ac.jp\/~OIO\/index.php?rest_route=\/wp\/v2\/posts\/2287","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/plaza.umin.ac.jp\/~OIO\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/plaza.umin.ac.jp\/~OIO\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/plaza.umin.ac.jp\/~OIO\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/plaza.umin.ac.jp\/~OIO\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=2287"}],"version-history":[{"count":0,"href":"https:\/\/plaza.umin.ac.jp\/~OIO\/index.php?rest_route=\/wp\/v2\/posts\/2287\/revisions"}],"wp:attachment":[{"href":"https:\/\/plaza.umin.ac.jp\/~OIO\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2287"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/plaza.umin.ac.jp\/~OIO\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2287"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/plaza.umin.ac.jp\/~OIO\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2287"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}