公开(公告)号：US20130166268A1

公开(公告)日：2013-06-27

申请号：US13533201

申请日：2012-06-26

申请人： Kristi A. Leonard ,  Richard Scott Alexander ,  Joseph Kent Barbay ,  Roger F. Bone ,  Ingrid Christa Deckman ,  Paul F. Jackson ,  Lawrence C. Kuo ,  Frank A. Lewandowski ,  Diane M. Maguire ,  Cynthia M. Milligan ,  Kenneth J. Rhodes ,  Robert H. Scannevin ,  Celine Schalk-Hihi ,  Barry Springer ,  John C. Spurlino ,  Matthew J. Todd ,  Brett Andrew Tongue ,  Aihua Wang

发明人： Kristi A. Leonard ,  Richard Scott Alexander ,  Joseph Kent Barbay ,  Roger F. Bone ,  Ingrid Christa Deckman ,  Paul F. Jackson ,  Lawrence C. Kuo ,  Frank A. Lewandowski ,  Diane M. Maguire ,  Cynthia M. Milligan ,  Kenneth J. Rhodes ,  Robert H. Scannevin ,  Celine Schalk-Hihi ,  Barry Springer ,  John C. Spurlino ,  Matthew J. Todd ,  Brett Andrew Tongue ,  Aihua Wang

IPC分类号： G06F19/12

CPC分类号： G06F19/706 ,  C12N9/6491 ,  G06F19/16 ,  G06F19/18 ,  Y02A90/26

摘要： The present invention includes a crystal comprising a complex of the pro form of a matrix metalloprotease (proMMP) and a small-molecule allosteric processing inhibitor that inhibits that activation of the proMMP, methods for identifying small-molecule allosteric processing inhibitors that inhibit the activation of a proMMP, and methods of treatment using small-molecule allosteric processing inhibitors that inhibit the activation of a proMMP. The present invention relates to the crystal structure of a complex of proMMP9 bound to a small-molecule allosteric processing inhibitor that inhibits activation of proMMP9. The invention further relates to the use of the methods and the crystal and related structural information for designing, selecting and/or optimizing small-molecule allosteric processing inhibitors that inhibit activation of proMMP9 and proMMP9 homologues. The present invention also relates to the use of small-molecule allosteric processing inhibitors for the treatment of diseases mediated by inappropriate matrix metalloproteinase (MMP) activity.

摘要翻译： 本发明包括晶体，其包含基质金属蛋白酶（proMMP）的形式的复合物和抑制该proMMP的激活的小分子变构的加工抑制剂，用于鉴定抑制激活的小分子变构加工抑制剂的方法 proMMP和使用抑制proMMP激活的小分子变构加工抑制剂的治疗方法。 本发明涉及与抑制proMMP9激活的小分子变构加工抑制剂结合的proMMP9的复合物的晶体结构。 本发明还涉及用于设计，选择和/或优化抑制proMMP9和proMMP9同源物激活的小分子变构加工抑制剂的方法和结晶及相关结构信息的使用。 本发明还涉及小分子变构加工抑制剂用于治疗由不适当的基质金属蛋白酶（MMP）活性介导的疾病的用途。

公开(公告)号：US20130040994A1

公开(公告)日：2013-02-14

申请号：US13533131

申请日：2012-06-26

申请人： Kristi A. Leonard ,  Richard Scott Alexander ,  Joseph Kent Barbay ,  Roger F. Bone ,  Carl Crysler ,  Ingrid Christa Deckman ,  Paul F. Jackson ,  Lawrence C. Kuo ,  Frank A. Lewandowski ,  Diane M. Maguire ,  Carl Manthey ,  Cynthia M. Milligan ,  Beverley Moore ,  Kenneth J. Rhodes ,  Robert H. Scannevin ,  Celine Schalk-Hihi ,  Barry Springer ,  John C. Spurlino ,  Matthew J. Todd ,  Brett Andrew Tongue ,  Aihua Wang

发明人： Kristi A. Leonard ,  Richard Scott Alexander ,  Joseph Kent Barbay ,  Roger F. Bone ,  Carl Crysler ,  Ingrid Christa Deckman ,  Paul F. Jackson ,  Lawrence C. Kuo ,  Frank A. Lewandowski ,  Diane M. Maguire ,  Carl Manthey ,  Cynthia M. Milligan ,  Beverley Moore ,  Kenneth J. Rhodes ,  Robert H. Scannevin ,  Celine Schalk-Hihi ,  Barry Springer ,  John C. Spurlino ,  Matthew J. Todd ,  Brett Andrew Tongue ,  Aihua Wang

IPC分类号： A61K31/427 ,  A61P35/00 ,  A61P19/02 ,  A61P9/00 ,  A61P1/04 ,  A61P9/12 ,  A61P11/00 ,  A61P1/02 ,  A61P17/02 ,  A61P1/16 ,  A61P9/10 ,  A61P25/00 ,  A61P11/06 ,  A61P13/12 ,  A61P25/06 ,  C12N9/99 ,  A61K31/4439

CPC分类号： A61K31/425 ,  A61K31/4439 ,  C07K2299/00 ,  G01N2333/96486

摘要： The present invention includes a crystal comprising a complex of the pro form of a matrix metalloprotease (proMMP) and a small-molecule allosteric processing inhibitor that inhibits that activation of the proMMP, methods for identifying small-molecule allosteric processing inhibitors that inhibit the activation of a proMMP, and methods of treatment using small-molecule allosteric processing inhibitors that inhibit the activation of a proMMP. The present invention relates to the crystal structure of a complex of proMMP9 bound to a small-molecule allosteric processing inhibitor that inhibits activation of proMMP9. The invention further relates to the use of the methods and the crystal and related structural information for designing, selecting and/or optimizing small-molecule allosteric processing inhibitors that inhibit activation of proMMP9 and proMMP9 homologues. The present invention also relates to the use of small-molecule allosteric processing inhibitors for the treatment of diseases mediated by inappropriate matrix metalloproteinase (MMP) activity.

摘要翻译： 本发明包括晶体，其包含基质金属蛋白酶（proMMP）的形式的复合物和抑制该proMMP活化的小分子变构加工抑制剂，用于鉴定抑制激活的小分子变构加工抑制剂的方法 proMMP和使用抑制proMMP激活的小分子变构加工抑制剂的治疗方法。 本发明涉及与抑制proMMP9激活的小分子变构加工抑制剂结合的proMMP9的复合物的晶体结构。 本发明还涉及用于设计，选择和/或优化抑制proMMP9和proMMP9同源物激活的小分子变构加工抑制剂的方法和结晶及相关结构信息的使用。 本发明还涉及小分子变构加工抑制剂用于治疗由不适当的基质金属蛋白酶（MMP）活性介导的疾病的用途。

公开(公告)号：US20130040360A1

公开(公告)日：2013-02-14

申请号：US13533108

申请日：2012-06-26

申请人： Kristi A. Leonard ,  Richard Scott Alexander ,  Joseph Kent Barbay ,  Roger F. Bone ,  Ingrid Christa Deckman ,  Paul F. Jackson ,  Lawrence C. Kuo ,  Frank A. Lewandowski ,  Diane M. Maguire ,  Cynthia M. Milligan ,  Kenneth J. Rhodes ,  Robert H. Scannevin ,  Celine Schalk-Hihi ,  Barry Springer ,  John C. Spurlino ,  Matthew J. Todd ,  Brett Andrew Tongue ,  Aihua Wang

发明人： Kristi A. Leonard ,  Richard Scott Alexander ,  Joseph Kent Barbay ,  Roger F. Bone ,  Ingrid Christa Deckman ,  Paul F. Jackson ,  Lawrence C. Kuo ,  Frank A. Lewandowski ,  Diane M. Maguire ,  Cynthia M. Milligan ,  Kenneth J. Rhodes ,  Robert H. Scannevin ,  Celine Schalk-Hihi ,  Barry Springer ,  John C. Spurlino ,  Matthew J. Todd ,  Brett Andrew Tongue ,  Aihua Wang

IPC分类号： C12N9/96

CPC分类号： C12N9/6491 ,  C12Y304/24017 ,  C12Y304/24035

摘要： The present invention includes a crystal comprising a complex of the pro form of a matrix metalloprotease (proMMP) and a small-molecule allosteric processing inhibitor that inhibits that activation of the proMMP, methods for identifying small-molecule allosteric processing inhibitors that inhibit the activation of a proMMP, and methods of treatment using small-molecule allosteric processing inhibitors that inhibit the activation of a proMMP. The present invention relates to the crystal structure of a complex of proMMP9 bound to a small-molecule allosteric processing inhibitor that inhibits activation of proMMP9. The invention further relates to the use of the methods and the crystal and related structural information for designing, selecting and/or optimizing small-molecule allosteric processing inhibitors that inhibit activation of proMMP9 and proMMP9 homologues. The present invention also relates to the use of small-molecule allosteric processing inhibitors for the treatment of diseases mediated by inappropriate matrix metalloproteinase (MMP) activity.