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    • 43. 发明公开
    • 평활근 세포 증식 억제제
    • 抑制剂增强平滑肌细胞
    • KR1020080077888A
    • 2008-08-26
    • KR1020070061579
    • 2007-06-22
    • 주식회사 앤씨비아이티한국화학연구원
    • 정광회박창식홍성유강수정손영덕황재훈최은복연규환이현규양희철
    • A61K31/47A61P35/00A61P21/00
    • A61K31/47Y10S514/824
    • A novel compound is provided to exhibit IC50 values of less than 0.16muM for vascular smooth muscle cells and cancer cells to prevent effectively proliferation of vascular smooth muscle cells and cancer cells, thereby ensuring prevention or treatment of hyperproliferative vascular disorders such as arteriosclerosis and restenosis, and cancers. A composition for inhibiting proliferation of smooth muscle cells comprises a compound represented by a formula(1) as an effective ingredient. In the formula(1), each R1, R2, R3, R4, R5, R6, and R7 is independently H, halo, hydroxy, cyano, amino, nitroso, carboxyl, C1-12 alkyl, C2-6 alkenyl, C3-8 cycloalkyl, C5-7 cycloalkenyl, C1-6 alkylamino, C1-6 alkoxy, aryl, heteroaryl, arylalkyl, arylalkenyl or alkylaryl; each X and Y is independently O or S; Z is H, halo, hydroxy, cyano, amino, nitro, nitroso, carboxyl, C1-12 alkyl, C2-6 alkenyl, C3-8 cycloalkyl, C5-7 cycloalkenyl, C1-6 alkylamino, C1-6 alkoxy, aryl, heteroaryl, arylalkyl, arylalkenyl, alkylaryl or -NH-R8; R8 is H, halo, hydroxy, cyano, amino, nitro, nitroso, carboxyl, C1-12 alkyl, C2-6 alkenyl, C3-8 cycloalkyl, C5-7 cycloalkenyl, C1-6 alkylamino, C1-6 alkoxy, aryl, heteroaryl, arylalkyl, arylalkenyl, or alkylaryl; and n is an integer from 0 to 3. A pharmaceutical composition for treating or preventing hyperproliferative vascular disorders comprises a pharmaceutically effective amount of the compound of the formula(1) and a pharmaceutically acceptable carrier.
    • 提供了一种新型化合物,以显示对于血管平滑肌细胞和癌细胞的IC 50值小于0.16muM,以防止血管平滑肌细胞和癌细胞的有效增殖,从而确保预防或治疗过度增殖性血管疾病如动脉硬化和再狭窄, 和癌症。 用于抑制平滑肌细胞增殖的组合物包含由式(1)表示的化合物作为有效成分。 在式(1)中,每个R 1,R 2,R 3,R 4,R 5,R 6和R 7独立地为H,卤素,羟基,氰基,氨基,亚硝基,羧基,C 1-12烷基,C 2-6烯基, 8环烷基,C 5-7环烯基,C 1-6烷基氨基,C 1-6烷氧基,芳基,杂芳基,芳基烷基,芳基烯基或烷基芳基; 每个X和Y独立地是O或S; Z是H,卤素,羟基,氰基,氨基,硝基,亚硝基,羧基,C 1-12烷基,C 2-6烯基,C 3-8环烷基,C 5-7环烯基,C 1-6烷基氨基,C 1-6烷氧基,芳基, 杂芳基,芳基烷基,芳基烯基,烷基芳基或-NH-R8; R8是H,卤素,羟基,氰基,氨基,硝基,亚硝基,羧基,C1-12烷基,C2-6烯基,C3-8环烷基,C5-7环烯基,C1-6烷基氨基,C1-6烷氧基,芳基, 杂芳基,芳基烷基,芳基烯基或烷基芳基; 并且n为0至3的整数。用于治疗或预防过度增殖性血管病症的药物组合物包含药学有效量的式(1)化合物和药学上可接受的载体。
    • 49. 发明公开
    • 인간 유래 조직형 플라스미노겐 활성화 인자의 대량발현용 재조합 유전자 및 그 단백질의 재구성 방법
    • 通过使用重组TPA基因的天然TPA蛋白质的氨基末端的生成人类组织型PLASMINOGEN激活剂(TPA)的重组基因,其中蛋白质可用性最大化的蛋白质可用性最大化和蛋白质重建方法
    • KR1020050018231A
    • 2005-02-23
    • KR1020030056597
    • 2003-08-14
    • 주식회사 앤씨비아이티
    • 정광회손영덕안수현최원석고유석
    • C12N15/12
    • C07K14/4702C07K1/1136C12N15/70
    • PURPOSE: A recombinant gene for mass production of human tissue type plasminogen activator(tPA) and a protein refolding method thereof are provided, which mass production of human tPA is accomplished by mutation of the amino terminal of a natural tPA protein using a recombinant tPA gene construct of which protein codon availability is maximized, and the recombinant tPA mass produced is refolded without loss of its activity. CONSTITUTION: The recombinant tissue type plasminogen activator(tPA) gene has the nucleotide sequence set forth in SEQ ID NO:1 wherein a codon in the nucleotide sequence of the amino terminal of the matured tPA protein. The recombinant tPA gene having the nucleotide sequence of SEQ ID NO:2 comprises the nucleotide sequence of SEQ ID NO:1 and a restriction enzyme BamHI site. An expression vector pMtPA comprises the recombinant tPA gene of SEQ ID NO:2. A transformed E. coli EMtPA (KCCM 10479) with the expression vector pMtPA is provided. The method for producing tPA comprises the steps of: (a) expressing a large quantity of the recombinant tPA inclusion body from the transformed E. coli EMtPA (KCCM 10479); (b) isolating the recombinant tPA inclusion body expressed; (c) treating the isolated the recombinant tPA inclusion body with unfolding solution; and (d) treating the unfolded recombinant protein in solution with a refolding reaction mixture and refolding the recombinant protein at 20 to 30 deg. C.
    • 目的:提供大量生产人体组织型纤溶酶原激活物(tPA)的重组基因及其蛋白质重折叠方法,通过使用重组tPA基因突变天然tPA蛋白的氨基末端来实现人类tPA的大规模生产 构建了最大化的蛋白质密码子可用性,并且所产生的重组tPA量重新折叠而不损失其活性。 构成:重组组织型纤溶酶原激活物(tPA)基因具有SEQ ID NO:1所示的核苷酸序列,其中成熟tPA蛋白的氨基末端的核苷酸序列中的密码子。 具有SEQ ID NO:2的核苷酸序列的重组tPA基因包含SEQ ID NO:1的核苷酸序列和限制酶BamHI位点。 表达载体pMtPA包含SEQ ID NO:2的重组tPA基因。 提供了具有表达载体pMtPA的转化的大肠杆菌EMtPA(KCCM 10479)。 生产tPA的方法包括以下步骤:(a)从转化的大肠杆菌EMtPA(KCCM10479)中表达大量的重组tPA包涵体; (b)分离表达的重组tPA包涵体; (c)用解折叠溶液处理分离的重组tPA包涵体; 和(d)用重折叠反应混合物处理溶液中未折叠的重组蛋白,并在20至30℃重新折叠重组蛋白。 C。