公开(公告)号：US20140200201A1

公开(公告)日：2014-07-17

申请号：US13780587

申请日：2013-02-28

申请人： Andrzej T. Slominski ,  Robert C. Tuckey ,  Blazej Zbytek ,  Michal A. Zmijewski ,  Minh Ngoc Nguyen ,  Zorica Janjetovic ,  Jianjun Chen ,  Wei Li ,  Duane D. Miller ,  Jordan K. Zjawiony ,  Arnold E. Postlethwaite ,  Trevor W. Sweatman

发明人： Andrzej T. Slominski ,  Robert C. Tuckey ,  Blazej Zbytek ,  Michal A. Zmijewski ,  Minh Ngoc Nguyen ,  Zorica Janjetovic ,  Jianjun Chen ,  Wei Li ,  Duane D. Miller ,  Jordan K. Zjawiony ,  Arnold E. Postlethwaite ,  Trevor W. Sweatman

IPC分类号： C07C401/00 ,  C12P7/02

CPC分类号： C07C401/00 ,  A61K8/63 ,  A61K2800/81 ,  A61K2800/94 ,  A61Q19/00 ,  C07J3/00 ,  C07J11/00 ,  C12P7/02

摘要： Provided herein are steroidal compounds that are androsta-5,7-dienes or a pregna-5,7-dienes and ultraviolet B (UVB) conversion products thereof which includes pharmaceutical compositions of the steroidal compounds as shown in Tables 1 and 2. Also provided is a method for producing hydroxylated metabolites of cholecalciferol or ergocalciferol via the P450scc (CYP11A1) or CYP27B1 enzyme systems where the hydroxylase has an activity to hydroxylate position C20 of a secosteroid or its 5,7-dieneal precursor and the hydroxylated metabolites so produced. In addition, a method for inhibiting proliferation of either a normally or abnormally proliferating cell by contacting the cell with any of the compounds described herein. A related method is provided of treating a condition associated with the proliferating cell such as a cancer, a skin disorder, a defect in cell differentiation, cosmetic, prophylaxsis, or healthy cell maintenance.

摘要翻译： 本文提供的是类固醇化合物，其是雄甾-5,7-二烯或其前体-5,7-二烯和紫外线B（UVB）转化产物，其包括如表1和2所示的甾体化合物的药物组合物。还提供 是通过P450scc（CYP11A1）或CYP27B1酶系统产生胆钙化醇或麦角钙化醇的羟化代谢物的方法，其中羟化酶具有使羟基化为羟基化的第二类固醇或其5,7-二醛前体的位置C20和如此生成的羟基化代谢物的活性。 此外，通过使细胞与本文所述的任何化合物接触来抑制正常或异常增殖细胞增殖的方法。 提供了一种相关方法来治疗与增殖细胞相关的病症，例如癌症，皮肤病症，细胞分化缺陷，化妆品，预防或健康细胞维持。

公开(公告)号：US06803359B2

公开(公告)日：2004-10-12

申请号：US09997498

申请日：2001-11-19

申请人： Edward T. Wei ,  Andrzej T. Slominski

发明人： Edward T. Wei ,  Andrzej T. Slominski

IPC分类号： C07K1400

CPC分类号： A61K38/2228

摘要： The glutamic acid residue of corticotropin-releasing hormone analogs have had the position 20 amino acid residue replaced with a D-amino acid moiety. The resulting CRH analogs do not significantly lower blood pressure but have anti-proliferative actions in cell culture and inhibit experimental cancer growth in animals (mice and rats). Novel applications of such analogs are described, such as to inhibit abnormal cell proliferation for conditions such as cancer, including melanoma, and for inflammatory dermatoses, such as psoriasis.

摘要翻译： 促肾上腺皮质激素释放激素类似物的谷氨酸残基具有被D-氨基酸部分替代的20个氨基酸残基。 所得到的CRH类似物不显着降低血压，但在细胞培养中具有抗增殖作用并抑制动物（小鼠和大鼠）中的实验性癌症生长。 描述了这种类似物的新型应用，例如抑制诸如癌症（包括黑素瘤）和炎性皮肤病如牛皮癣等疾病的异常细胞增殖。

公开(公告)号：US06319900B1

公开(公告)日：2001-11-20

申请号：US09400716

申请日：1999-09-21

申请人： Edward T. Wei ,  Andrzej T. Slominski

发明人： Edward T. Wei ,  Andrzej T. Slominski

IPC分类号： C02K1400

CPC分类号： A61K38/2228

摘要： The glutamic acid residue of corticotropin-releasing hormone analogs have had the position 20 amino acid residue replaced with a D-amino acid moiety. The resulting CRH analogs do not significantly lower blood pressure but have anti-proliferative actions in cell culture and inhibit experimental cancer growth in animals (mice and rats). Novel applications of such analogs are described, such as to inhibit abnormal cell proliferation for conditions such as cancer, including melanoma, and for inflammatory dermatoses, such as psoriasis.

摘要翻译： 促肾上腺皮质激素释放激素类似物的谷氨酸残基已经被20个氨基酸残基置换为 D - 氨基酸部分。 所得到的CRH类似物不显着降低血压，但在细胞培养中具有抗增殖作用并抑制动物（小鼠和大鼠）中的实验性癌症生长。 描述了这种类似物的新型应用，例如抑制诸如癌症（包括黑素瘤）和炎性皮肤病如牛皮癣等疾病的异常细胞增殖。