國鼎Antroquinonol 獲FDA孤兒藥資格 (AMPK activation & mTOR inhibition ) !!

國鼎生技：本公司研發中血液腫瘤類之急性骨髓性白血病小分子新藥，獲得美國食品藥物管理局(FDA)核准通過孤兒藥資格 鉅亨網新聞中心2015-05-04 15:36:13　 第三十四條　第42款1.事實發生日:104/05/04-->2.公司名稱:國鼎生技股份有限公司3.與公司關係(請輸入本公司或聯屬公司):本公司4.相互持股比例(若前項為本公司，請填不適用):不適用5.發生緣由:本公司新藥Antroquinonol獲得美國食品藥物管理局(FDA)通知，正式取得血液腫瘤類之急性骨髓性白血病孤兒藥資格認定(15-4763)，經美國FDA認定為「孤兒藥」的藥品，除可獲得美國研究經費補助外，藥物主管機關更給予行政協助及市場專賣保護期等優惠措施。因為按孤兒藥程序進行臨床試驗，藉由FDA主動協助，將縮短取得藥證之時間。6.因應措施:無7.其他應敘明事項:(1)研發新藥名稱或代號：GHAML(Antroquinonol)(2)用途：一種治療急性骨髓性白血病小分子新藥(3)預計進行之所有研發階段：口服劑型：二、三期臨床試驗(需與美國食品藥物管理局協商確認)、FDA新藥查驗登記審查。(4)目前進行中之研發階段：A.提出申請/通過核准/不通過核准：本公司已獲得美國食品藥物管理局認證治療急性骨髓性白血病孤兒藥(15-4763)B.未通過目的事業主管機關許可者，公司所面臨之風險及因應措施：不適用C.已通過目的事業主管機關許可者，未來經營方向：本公司將依原先年度計畫，繼續研發完成急性骨髓性白血病之臨床試驗，獲得孤兒藥資格將適用美國的獎勵措施有效降低本公司研發支出。D.已投入之研發費用：已完成臨床前之相關試驗與一期臨床試驗。(5)將再進行之下一階段研發：A.預計完成時間：口服劑型臨床試驗規劃及範圍，需依據與美國食品藥物管理局討論審核結果而定，若一切順利完成，預計試驗完成時間約在106年。B.預計應負擔之義務：該小分子新藥係國鼎生技獨立研發,擁有100%專利權, 僅須完成相關臨床試驗。(6)新藥開發時程長、投入經費高且未保證一定能成功，此等可能使投資面臨風險，投資人應審慎判斷謹慎投資。

Antroquinonol displays anticancer potential against human hepatocellular carcinoma cells: a crucial role of AMPK and mTOR pathways.  Biochem Pharmacol. 2010 Jan 15;79(2):162-71.

Abstract 5'AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR) are two serine/threonine protein kinases responsible for cellular energy homeostasis and translational control, respectively. Evidence suggests that these two kniases are potential targets for cancer chemotherapy against hepatocellular carcinoma (HCC). Antroquinonol that is isolated from Antrodia camphorate, a well-known Traditional Chinese Medicine for treatment of liver diseases, displayed effective anticancer activity against both HBV DNA-positive and -negative HCC cell lines. The rank order of potency against HCCs is HepG2>HepG2.2.15>Mahlavu>PLC/PRF/5>SK-Hep1>Hep3B. Antroquinonol completely abolished cell-cycle progression released from double-thymidine-block synchronization and caused a subsequent apoptosis. The data were supported by down-regulation and reduced nuclear translocation of G1-regulator proteins, including cyclin D1, cyclin E, Cdk4 and Cdk2. Further analysis showed that the mRNA expressions of the G1-regulator proteins were not modified by antroquinonol, indicating an inhibition of translational but not transcriptional levels. Antroquinonol induced the assembly of tuberous sclerosis complex (TSC)-1/TSC2, leading to the blockade of cellular protein synthesis through inhibition of protein phosphorylation including mTOR (Ser(2448)), p70(S6K) (Thr(421)/Ser(424) and Thr(389)) and 4E-BP1 (Thr(37)/Thr(46) and Thr(70)). Furthermore, the AMPK activity was elevated by antroquinonol. Compound C, a selective AMPK inhibitor, significantly reversed antroquinonol-mediated effects suggesting the crucial role of AMPK. Besides, the loss of mitochondrial membrane potential and depletion of mitochondrial content indicated the mitochondrial stress caused by antroquinonol. In summary, the data suggest that antroquinonol displays anticancer activity against HCCs through AMPK activation and inhibition of mTOR translational pathway, leading to G1 arrest of the cell-cycle and subsequent cell apoptosis.