To screen for compounds that protec

To screen for compounds that protect hair cells against ototoxic drugs, only minor modifications are necessary to our toxicity screens.

Our initial screens for hair cell protectants were designed to identify compounds that conferred robust protection to neomycin-treated hair cells [26].

We initially focused on small molecules within the Chembridge Diverset E library.

To efficiently screen a sample of 10,960 compounds from the library, compounds were multiplexed five per well and then reassessed individually when protection was observed.

Two compounds, PROTO1 and PROTO2, exhibited robust protection of lateral line hair cells over a broad range of neomycin concentrations.

Further testing of these compounds in mice revealed that they also protected hair cells in neomycintreated utricular explants, validating the zebrafish lateral line as a model for discovery of novel otoprotective drugs.

Both PROTO1 and PROTO2 are related benzothiophene carboximides, raising the possibility that they may confer their protective effects through action on the same target.

結果 (繁體中文) 2:

為了篩選保護毛細胞免受耳毒性藥物的化合物，只有輕微的修改是必要的，以我們的毒性的屏幕。我們的初始畫面為毛細胞保護劑被設計以鑑定賦予強有力的保護，以新黴素治療的毛細胞[26]的化合物。我們最初集中在ChemBridge公司DiversetÈ文庫內的小分子。為了有效地篩選的從庫10960化合物的樣品，將化合物多路復用5每孔，然後分別重新評估時，觀察保護。兩種化合物，PROTO1和PROTO2，顯示出強有力的保護的橫向線毛細胞在寬範圍新黴素濃度。這些化合物在小鼠中進一步測試表明，它們也保護毛細胞neomycintreated橢圓囊外植體，驗證所述斑馬魚側線作為一個模型用於發現新穎otoprotective藥物。這兩種PROTO1和PROTO2是相關苯並噻吩carboximides，提高他們可以通過行動賦予同一個目標的保護作用的可能性。

結果 (繁體中文) 3:

篩選的化合物，保護毛細胞對耳毒性藥物，只有輕微的修改是必要的我們的毒性實驗。我們

毛細胞保護劑的初始荧幕的目的是確定化合物賦予强大的保護，對新黴素治療毛細胞[ 26 ]。

我們最初專注於小分子內的電子圖書館diverset CHEMBRIDGE。

有效地篩選10960個化合物樣品庫，化合物五為好，然後再複用時單獨保護觀察。

兩化合物，proto1和proto2，表現出强大的保護毛細胞的橫向線在一個廣泛的新黴素濃度。

在小鼠中這些化合物的進一步的測試表明，他們也保護毛細胞neomycintreated橢圓囊外植體，驗證斑馬魚側線作為一種新型耳保護藥物發現模式。

都proto1和proto2與苯並噻吩carboximides，提高他們可能賦予他們的保護作用通過對同一目標行動的可能性。