JP2016505013A - 皮膚の再生を促進する小分子 - Google Patents
皮膚の再生を促進する小分子 Download PDFInfo
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- JP2016505013A JP2016505013A JP2015552749A JP2015552749A JP2016505013A JP 2016505013 A JP2016505013 A JP 2016505013A JP 2015552749 A JP2015552749 A JP 2015552749A JP 2015552749 A JP2015552749 A JP 2015552749A JP 2016505013 A JP2016505013 A JP 2016505013A
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Abstract
Description
本出願は、米国特許法第119条(e)の下、2013年1月9日に提出された米国特許出願第61/750,714号の優先権の利益を主張し、その全体が参照することにより本出願に援用される。
本発明は、概して皮膚再生および創傷治癒に関するものであり、より具体的には、ヒト皮膚線維芽細胞の増殖およびタンパク質産生の増加の小分子媒介性誘導に関する。
脊椎動物の身体の最大の器官である皮膚は、複雑な神経および血液供給を伴う表皮および真皮から構成される。第三層、皮下組織は、主に脂肪と疎性結合組織の層で構成されている。これらの三層は、創傷等の任意の機械的損傷から身体を保護する上で重要な役割を果たしている。
皮膚線維芽細胞は、コラーゲンの生産に責任を担う皮膚細胞であり、皮膚バリアの完全性および創傷治癒を促進する結合組織の線維および成長因子の形成に寄与する。正常な創傷治癒では、線維芽細胞が周囲の無傷の組織から肉芽組織へ補充され、創傷流体中で提示された様々な因子に反応して、新しい真皮層を増殖し再生する。正常な老化の間、真皮線維芽細胞は、増殖する能力と、正常な創傷治癒に関与する成長因子(例えば、EGF、FGF7/KGF、TGFβ、コラーゲン)を分泌する能力の両方を失う。線維芽細胞の増殖を促進し、タンパク質の分泌(例えば、EGF、FGF7/KGF、TGFβ、コラーゲン)を増加させる小分子を同定するために設計されたハイスループットスクリーニングを、本明細書に記載する。
ヒト皮膚線維芽細胞(hDF)の増殖のためのハイスループット増殖スクリーニングアッセイ
FGF7生産のためのハイスループットスクリーニングアッセイ
TGFβ1生産のためのハイスループットスクリーニングアッセイ
EGF生産のためのハイスループットスクリーニングアッセイ
1型コラーゲン生産のためのハイスループットスクリーニングアッセイ
Claims (20)
- 線維芽細胞の増殖を誘導する有効量の小分子を対象に投与する工程を含む、線維芽細胞の増殖をインビトロまたはインビボで対象において誘導する方法。
- 対象がヒトである、請求項1に記載の方法。
- 線維芽細胞がヒト皮膚線維芽細胞(hDF)の細胞である、請求項1に記載の方法。
- 小分子が、SL 327、ABT 702、フェノバム、SX 011、フィゾスチグミン硫酸塩およびNBQXからなる群から選択される、請求項1に記載の方法。
- タンパク質分泌を増加させる有効量の小分子を対象に投与する工程を含む、対象のタンパク質の分泌を増加させる方法。
- 対象がヒトである、請求項5に記載の方法。
- 線維芽細胞がヒト皮膚線維芽細胞(hDF)の細胞である、請求項5に記載の方法。
- タンパク質が、EGF、FGF7、KGF、TGFβおよびコラーゲンからなる群から選択される、請求項5に記載の方法。
- 小分子が、CY 208−243、CD 439、T 0156塩酸塩、CD 1530、PSB 06126、プロスタグランジンE2、LY 294002塩酸塩、KB−R7943、メシル酸塩、プロキシファンシュウ酸塩、m−3M3FBS、ジピリダモール、メチルリカコニチンクエン酸塩、WIN 64338、フマル酸クレマスチンおよびシロスタゾールからなる群から選択される、請求項5に記載の方法。
- タンパク質がEGFであり、小分子が、CY 208−243、CD 439、T 0156塩酸塩、CD 1530およびPSB 06126からなる群から選択される、請求項5に記載の方法。
- タンパク質がFGF7/KGFであり、小分子がプロスタグランジンE2である、請求項5に記載の方法。
- タンパク質がTGFβであり、小分子が、LY 294002塩酸塩、KB−R7943メシル酸塩、プロキシファンシュウ酸塩およびm−3M3FBSからなる群から選択される、請求項5に記載の方法。
- タンパク質がコラーゲンIであり、小分子が、ジピリダモール、メチルリカコニチンクエン酸塩、WIN 64338、フマル酸クレマスチンおよびシロスタゾールからなる群から選択される、請求項5に記載の方法。
- 線維芽細胞の増殖を誘導する有効量の化合物を対象に投与する工程を含む、皮膚の再生を促進する方法。
- 対象がヒトである、請求項14に記載の方法。
- 線維芽細胞が皮膚線維芽細胞(hDF)の細胞である、請求項14に記載の方法。
- 小分子が、SL 327、ABT 702、フェノバム、SX 011、フィゾスチグミン硫酸塩およびNBQXからなる群から選択される、請求項14に記載の方法。
- タンパク質分泌を増加させる有効量の化合物を対象に投与する工程を含む、皮膚の再生を促進する方法。
- タンパク質が、EGF、FGF7/KGF、TGFβおよびコラーゲンからなる群から選択される、請求項19に記載の方法。
- タンパク質が、CY 208−243、CD 439、T 0156塩酸塩、CD 1530、PSB 06126、プロスタグランジンE2、LY 294002塩酸塩、KB−R7943メシル酸塩、プロキシファンシュウ酸塩、m−3M3FBS、ジピリダモール、メチルリカコニチンクエン酸塩、WIN 64338、フマル酸クレマスチンおよびシロスタゾールからなる群から選択される、請求項19に記載の方法。
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CN104903439B (zh) | 2019-01-04 |
GB201514085D0 (en) | 2015-09-23 |
US20160303145A1 (en) | 2016-10-20 |
WO2014110177A3 (en) | 2015-03-05 |
HK1209038A1 (en) | 2016-03-24 |
GB2524707A (en) | 2015-09-30 |
JP6509126B2 (ja) | 2019-05-08 |
US10335422B2 (en) | 2019-07-02 |
EP2943564A2 (en) | 2015-11-18 |
KR102263013B1 (ko) | 2021-06-10 |
US20140309195A1 (en) | 2014-10-16 |
WO2014110177A2 (en) | 2014-07-17 |
CN104903439A (zh) | 2015-09-09 |
EP2943564A4 (en) | 2016-10-26 |
MX2015008997A (es) | 2016-04-15 |
US9375439B2 (en) | 2016-06-28 |
MX370838B (es) | 2020-01-08 |
GB2524707B (en) | 2020-04-22 |
KR20150103014A (ko) | 2015-09-09 |
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