公开(公告)号：US20080108569A1

公开(公告)日：2008-05-08

申请号：US11910389

申请日：2006-03-31

申请人： Alexandra Newton ,  Tianyan Gao ,  John Brognard

发明人： Alexandra Newton ,  Tianyan Gao ,  John Brognard

IPC分类号： A61K38/00 ,  G01N33/53 ,  C12Q1/68 ,  C12N5/00

CPC分类号： C07K16/40 ,  A61K38/465 ,  C12N9/16 ,  G01N2333/916 ,  G01N2500/04 ,  G01N2510/00

摘要： The present invention relates generally to PHLPP, a novel phosphatase that inactivates Akt (protein kinase B) by directly dephosphorylating the hydrophobic domain of the C-terminus. More specifically, the invention relates to PHLPP polynucleotides and the polypeptides encoded by these polynucleotides and the use of these polynucleotides and polypeptides in the treatment and diagnosis of biological conditions mediated by Akt phosphorylation, particularly cancer. This invention relates to PHLPP polynucleotides and polypeptides as well as vectors, host cells, antibodies directed to PHLPP polynucleotides and polypeptides and recombinant and synthetic methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of PHLPP polynucleotides and polypeptides of the invention.

摘要翻译： 本发明一般涉及通过直接去磷酸化C-末端的疏水结构域而使Akt（蛋白激酶B）失活的新型磷酸酶。 更具体地，本发明涉及PHLPP多核苷酸和由这些多核苷酸编码的多肽以及这些多核苷酸和多肽在治疗和诊断由Akt磷酸化，特别是癌症介导的生物学条件中的用途。 本发明涉及PHLPP多核苷酸和多肽以及载体，宿主细胞，针对PHLPP多核苷酸和多肽的抗体以及用于制备其的重组和合成方法。 本发明还涉及用于鉴定本发明的PHLPP多核苷酸和多肽的激动剂和拮抗剂的筛选方法。

公开(公告)号：US20050272708A1

公开(公告)日：2005-12-08

申请号：US10526851

申请日：2003-09-03

申请人： Alan Kozikowski ,  Phillip Denis ,  Haiying Sun ,  John Brognard

发明人： Alan Kozikowski ,  Phillip Denis ,  Haiying Sun ,  John Brognard

IPC分类号： A61K31/683 ,  A61K31/66 ,  A61P9/00 ,  A61P11/00 ,  A61P11/08 ,  A61P15/00 ,  A61P17/00 ,  A61P19/02 ,  A61P25/00 ,  A61P29/00 ,  A61P31/04 ,  A61P31/12 ,  A61P31/14 ,  A61P33/00 ,  A61P35/00 ,  A61P35/02 ,  A61P43/00 ,  C07C43/196 ,  C07F9/02 ,  C07F9/117

CPC分类号： C07C43/196 ,  C07C2601/14 ,  C07F9/117

摘要： Disclosed are inhibitors of the serine/threonine kinase Akt, pharmaceutical compositions comprising such inhibitors, and a method of preventing or treating a disease or condition in an animal by the use of such inhibitors. The Akt inhibitors have the formula (I) wherein X and Y are independently selected from the group consisting of O, CF2, CH2, and CHF; wherein A is independently selected from the group consisting of P(O)OH, CH2000H, and CH(COOH)2; R2 is selected from the group consisting of H, OH, isosteres of OH, C1-C25 alkyloxy, C6-C10 aryloxy, C3-C8 cycloalkyloxy, C3-C8 cycloalkyl C1-C6 alkoxy, C2-C22 alkenyloxy, C3-C8 cycloalkenyloxy, C7-C32 aralkyloxy, C7-C32 alkylaryloxy, C9-C32 aralkenyloxy, and C9-C32 alkenylaryloxy; R3-R6 are independently selected from the group consisting of H, OH, isosteres of OH; and R1 and R7 are independently selected from the group consisting of C1-C25 alkyl, C6-C10 aryl, C3-C8 cycloalkyl, C2-C22 alkenyl, C3-C8 cycloalkenyl, C7-C32 aralkyl, C7-C32 alkylaryl, C9-C32 aralkenyl, and C9-C32 alkenylaryl; with the provisos that (i) when X is O, Y is O or CH2, and R3 is H, at least one of R2 and R4-R6 is not OH; (ii) when A is CH2COOH or CH(COOH)2, X and Y cannot be simultaneously O; and (iii) all of R2-R6 are not simultaneously H. The inhibitors can be in the form of a salt also.

公开(公告)号：US07378403B2

公开(公告)日：2008-05-27

申请号：US10526851

申请日：2003-09-03

申请人： Alan P. Kozikowski ,  Phillip Dennis ,  Haiying Sun ,  John Brognard

发明人： Alan P. Kozikowski ,  Phillip Dennis ,  Haiying Sun ,  John Brognard

IPC分类号： A61K31/662 ,  A61K31/683 ,  C07F9/09 ,  C07F9/30

CPC分类号： C07C43/196 ,  C07C2601/14 ,  C07F9/117

摘要： Disclosed are inhibitors of the serine/threonine kinase Akt, pharmaceutical compositions comprising such inhibitors, and a method of preventing or treating a disease or condition in an animal by the use of such inhibitors. The Akt inhibitors have the formula (I) wherein X and Y are independently selected from the group consisting of O, CF2, CH2, and CHF; wherein A is independently selected from the group consisting of P(O)OH, CH2000H, and CH(COOH)2; R2 is selected from the group consisting of H, OH, isosteres of OH, C1-C25 alkyloxy, C6-C10 aryloxy, C3-C8 cycloalkyloxy, C3-C8 cycloalkyl C1-C6 alkoxy, C2-C22 alkenyloxy, C3-C8 cycloalkenyloxy, C7-C32 aralkyloxy, C7-C32 alkylaryloxy, C9-C32 aralkenyloxy, and C9-C32 alkenylaryloxy; R3-R6 are independently selected from the group consisting of H, OH, isosteres of OH; and R1 and R7 are independently selected from the group consisting of C1-C25 alkyl, C6-C10 aryl, C3-C8 cycloalkyl, C2-C22 alkenyl, C3-C8 cycloalkenyl, C7-C32 aralkyl, C7-C32 alkylaryl, C9-C32 aralkenyl, and C9-C32 alkenylaryl; with the provisos that (i) when X is O, Y is O or CH2, and R3 is H, at least one of R2 and R4-R6 is not OH; (ii) when A is CH2COOH or CH(COOH)2, X and Y cannot be simultaneously O; and (iii) all of R2-R6 are not simultaneously H. The inhibitors can be in the form of a salt also