公开(公告)号：US20160244457A1

公开(公告)日：2016-08-25

申请号：US15147648

申请日：2016-05-05

Applicant: UNIVERSITY OF KANSAS ,  STC.UNM

Inventor： Richard Smith Larson ,  Larry A. Sklar ,  Bruce S. Edwards ,  Juan Jacob Strouse ,  Irena lvnitski-Steele ,  Hadya M. Khawaja ,  Jerec Warren Ricci ,  Jeffrey Aube ,  Jennifer Elizabeth Golden ,  TuanIi Yao ,  Warren S. Weiner ,  Chad E. Schroeder

IPC: C07D487/04 ,  A61K31/4745 ,  A61K31/519

CPC classification number: C07D487/04 ,  A61K31/437 ,  A61K31/4745 ,  A61K31/519 ,  A61K45/06

Abstract: The present invention provides novel compounds which inhibit cancer-associated transporter proteins, methods of treating or preventing the onset of a cancer-associated transporter protein-mediated disease by administering such compounds, and pharmaceutical compositions comprising such compounds. In one embodiment, the invention provides novel pyrazolo[1,5-a]pyrimidine efflux inhibitors that are selective toward ABCG2 over ABCB1.

公开(公告)号：US20150197526A1

公开(公告)日：2015-07-16

申请号：US14587925

申请日：2014-12-31

Applicant: STC.UNM ,  UNIVERSITY OF KANSAS

Inventor： Richard Smith Larson ,  Larry A. Sklar ,  Bruce S. Edwards ,  Juan Jacob Strouse ,  Irena Ivnitski-Steele ,  Hydya M. Khawaja ,  Jerec Warren Ricci ,  Jeffrey Aube ,  Jennifer Elizabeth Golden ,  Tuanli Yao ,  Warren S. Weiner ,  Chad E. Schroeder

IPC: C07D487/04 ,  A61K31/4745 ,  A61K45/06 ,  A61K31/519

CPC classification number: C07D487/04 ,  A61K31/437 ,  A61K31/4745 ,  A61K31/519 ,  A61K45/06

Abstract: The present invention provides novel compounds which inhibit cancer-associated transporter proteins, methods of treating or preventing the onset of a cancer-associated transporter protein-mediated disease by administering such compounds, and pharmaceutical compositions comprising such compounds. In one embodiment, the invention provides novel pyrazolo[1,5-a]pyrimidine efflux inhibitors that are selective toward ABCG2 over ABCB1.

Abstract translation: 本发明提供抑制癌症相关转运蛋白的新型化合物，通过施用这些化合物治疗或预防癌症相关转运蛋白介导的疾病发作的方法，以及包含这些化合物的药物组合物。 在一个实施方案中，本发明提供了关于ABCB1对ABCG2有选择性的新型吡唑并[1,5-a]嘧啶外排抑制剂。

公开(公告)号：US09056111B1

公开(公告)日：2015-06-16

申请号：US13622651

申请日：2012-09-19

Applicant: STC.UNM ,  UNIVERSITY OF KANSAS

Inventor： Richard Smith Larson ,  Larry A. Sklar ,  Bruce S. Edwards ,  Juan Jacob Strouse ,  Irena Ivnitski-Steele ,  Hadya M. Khawaja ,  Jerec Warren Ricci ,  Jeffrey Aube ,  Jennifer Elizabeth Golden ,  Tuanli Yao ,  Warren S. Weiner ,  Chad E. Schroeder

IPC: A01N43/90 ,  A61K31/519 ,  C07D487/00 ,  A61K31/437 ,  C07D487/04

CPC classification number: C07D487/04 ,  A61K31/437 ,  A61K31/4745 ,  A61K31/519 ,  A61K45/06

Abstract: The present invention provides pyrazolo[1,5-a]pyrimidine compounds which inhibit cancer-associated transporter proteins, methods of treating or preventing the onset of a cancer-associated transporter protein-mediated disease by administering such compounds, and pharmaceutical compositions comprising such compounds. In one embodiment, the invention provides pyrazolo[1,5-a]pyrimidine efflux inhibitors that are selective toward ABCG2 over ABCB1. Compounds and compositions according to the present invention may be used to treat cancer, including drug resistant (DR) and multiple drug resistant (MDR) cancers.

Abstract translation: 本发明提供了抑制癌症相关转运蛋白的吡唑并[1,5-a]嘧啶化合物，通过施用这些化合物来治疗或预防与癌症相关的转运蛋白介导的疾病发作的方法，以及包含这些化合物的药物组合物 。 在一个实施方案中，本发明提供对ABCB1而言对ABCG2有选择性的吡唑并[1,5-a]嘧啶外排抑制剂。 根据本发明的化合物和组合物可用于治疗癌症，包括耐药性（DR）和多重耐药性（MDR）癌症。

公开(公告)号：US20160320402A1

公开(公告)日：2016-11-03

申请号：US15013102

申请日：2016-02-02

Applicant: STC.UNM ,  TORREY PINES INSTITUTE FOR MOLECULAR STUDIES

Inventor： Bruce S. Edwards ,  Larry A. Sklar ,  Clemencia Pinilla ,  Richard A. Houghten ,  Jon R. Appel ,  Marc A. Giulianotti ,  Jose Medina-Franco

IPC: G01N33/68 ,  A61K31/17 ,  A61K31/496 ,  C40B30/02 ,  G01N33/74

CPC classification number: G01N33/6845 ,  A61K31/17 ,  A61K31/496 ,  A61K38/00 ,  A61K45/06 ,  B01J2219/00585 ,  C07C275/28 ,  C07D241/08 ,  C07D403/14 ,  C07K1/047 ,  C40B30/02 ,  G01N33/74 ,  G01N2333/726 ,  A61K2300/00

Abstract: The present invention provides novel methods and assays for high-throughput screening of combinatorial libraries to identify FPR1 and/or FPR2 ligands (e.g., agonists and/or antagonists), preferably FPR1 agonists and/or FPR2 antagonists, by positional scanning deconvolution.The invention also provides novel FPR1 and FPR2 ligands (e.g, agonists and antagonists), related pharmaceutical compositions and methods of treating FPR1 and FPR2-related disorders.

Abstract translation: 本发明还提供新的FPR1和FPR2配体（例如激动剂和拮抗剂），相关的药物组合物和治疗FPR1和FPR2相关疾病的方法。

公开(公告)号：US10048272B2

公开(公告)日：2018-08-14

申请号：US15013102

申请日：2016-02-02

Applicant: STC.UNM ,  TORREY PINES INSTITUTE FOR MOLECULAR STUDIES

Inventor： Bruce S. Edwards ,  Larry A. Sklar ,  Clemencia Pinilla ,  Richard A. Houghten ,  Jon R. Appel ,  Marc A. Giulianotti ,  Jose Medina-Franco

IPC: A61K31/497 ,  A61K31/517 ,  A61K31/17 ,  G01N33/68 ,  C07D403/14 ,  A61K31/496 ,  A61K45/06 ,  C07C275/28 ,  C40B30/02 ,  G01N33/74 ,  A61K38/00 ,  C07D241/08 ,  C07K1/04

Abstract: The present invention provides novel methods and assays for high-throughput screening of combinatorial libraries to identify FPR1 and/or FPR2 ligands (e.g., agonists and/or antagonists), preferably FPR1 agonists and/or FPR2 antagonists, by positional scanning deconvolution.The invention also provides novel FPR1 and FPR2 ligands (e.g, agonists and antagonists), related pharmaceutical compositions and methods of treating FPR1 and FPR2-related disorders.

公开(公告)号：US09326974B2

公开(公告)日：2016-05-03

申请号：US14449957

申请日：2014-08-01

Applicant: STC.UNM

Inventor： Todd A. Thompson ,  Debra Mackenzie ,  Tudor I. Oprea ,  Larry A. Sklar ,  Bruce S. Edwards ,  Mark Haynes

IPC: A01N43/66 ,  A61K31/437 ,  A61K31/165 ,  A61K31/445 ,  A61K31/135 ,  A61K45/06 ,  A61N5/10

CPC classification number: A61K31/437 ,  A61K31/135 ,  A61K31/165 ,  A61K31/445 ,  A61K45/06 ,  A61N5/10

Abstract: A method of treatment and/or prevention of cancer comprises administering agents which cause increased intracellular granularity in cancer cells, at least in an amount sufficient to inhibit proliferation of such cells and preferably in an amount sufficient to lead to cancer cell death. The method is particularly directed to refractory cancer, particularly hormone refractory prostate cancer. The agents identified cause increased intracellular granularity in the cancer cells, and also convert adherent cancer cells to non-adherent cancer cells, leading to cancer cell death. Using the present invention, cancer cells undergo increased intracellular granularity at relatively low agent concentrations, while also inhibiting cell proliferation. Increased concentrations lead to conversion of adherent cancer cells to non-adherent cancer cells, then to cell death. While the exact mechanism of cancer cell degradation and death is not completely understood, the treated cancer cells, including refractory prostate cancer cells, give indications of cell death through an autophagic mechanism. Pharmaceutical compositions related to the presently disclosed methods are also disclosed.

Abstract translation: 治疗和/或预防癌症的方法包括在癌细胞中引起增加的细胞内颗粒度的给药剂，至少足以抑制这些细胞增殖的量，优选以足以导致癌细胞死亡的量。 该方法特别涉及难治性癌症，特别是激素难治性前列腺癌。 所鉴定的试剂导致癌细胞中的细胞内颗粒度增加，并且将粘附的癌细胞转化为非贴壁癌细胞，导致癌细胞死亡。 使用本发明，癌细胞在相对低的药物浓度下经历增加的细胞内粒度，同时也抑制细胞增殖。 增加的浓度导致粘附的癌细胞转化为非粘附的癌细胞，然后转移到细胞死亡。 虽然癌细胞降解和死亡的确切机制尚未完全了解，但治疗的癌细胞（包括难治性前列腺癌细胞）通过自噬机制给予细胞死亡的指示。 还公开了与目前公开的方法相关的药物组合物。

公开(公告)号：US09752964B1

公开(公告)日：2017-09-05

申请号：US13717279

申请日：2012-12-17

Applicant: STC.UNM

Inventor： Bruce S. Edwards ,  Larry A. Sklar ,  Ronald D. Salesky

IPC: G01N21/00 ,  G01N15/06 ,  G01N33/00 ,  G01N1/14

CPC classification number: G01N1/14 ,  G01N15/1459 ,  G01N35/08 ,  G01N35/109

Abstract: A flow cytometry apparatus includes a flow cytometer having a suction or negative-pressure intake probe, a support for a microplate having a plurality of sample wells, and motive elements operatively connected to at least one of the probe and the support for moving the intake probe and the support relative to one another so that the intake probe is sequentially aligned with different sample wells of the microplate. The apparatus has no fluid pumping elements between the support and the flow cytometer so that a bubble-separated sample stream is forced to the flow cytometer solely by virtue of a negative pressure communicated via the intake probe.

公开(公告)号：US20140343347A1

公开(公告)日：2014-11-20

申请号：US14449957

申请日：2014-08-01

Applicant: STC.UNM

Inventor： Todd A. Thompson ,  Debra Mackenzie ,  Tudor I. Oprea ,  Larry A. Sklar ,  Bruce S. Edwards ,  Mark Haynes

IPC: A61K31/437 ,  A61K45/06 ,  A61N5/10 ,  A61K31/135

CPC classification number: A61K31/437 ,  A61K31/135 ,  A61K31/165 ,  A61K31/445 ,  A61K45/06 ,  A61N5/10

Abstract: A method of treatment and/or prevention of cancer comprises administering agents which cause increased intracellular granularity in cancer cells, at least in an amount sufficient to inhibit proliferation of such cells and preferably in an amount sufficient to lead to cancer cell death. The method is particularly directed to refractory cancer, particularly hormone refractory prostate cancer. The agents identified cause increased intracellular granularity in the cancer cells, and also convert adherent cancer cells to non-adherent cancer cells, leading to cancer cell death. Using the present invention, cancer cells undergo increased intracellular granularity at relatively low agent concentrations, while also inhibiting cell proliferation. Increased concentrations lead to conversion of adherent cancer cells to non-adherent cancer cells, then to cell death. While the exact mechanism of cancer cell degradation and death is not completely understood, the treated cancer cells, including refractory prostate cancer cells, give indications of cell death through an autophagic mechanism. Pharmaceutical compositions related to the presently disclosed methods are also disclosed.

Abstract translation: 治疗和/或预防癌症的方法包括在癌细胞中引起增加的细胞内颗粒度的给药剂，至少足以抑制这些细胞增殖的量，优选以足以导致癌细胞死亡的量。 该方法特别涉及难治性癌症，特别是激素难治性前列腺癌。 所鉴定的试剂导致癌细胞中的细胞内颗粒度增加，并且将粘附的癌细胞转化为非贴壁癌细胞，导致癌细胞死亡。 使用本发明，癌细胞在相对低的药物浓度下经历增加的细胞内粒度，同时也抑制细胞增殖。 增加的浓度导致粘附的癌细胞转化为非粘附的癌细胞，然后转移到细胞死亡。 虽然癌细胞降解和死亡的确切机制尚未完全了解，但治疗的癌细胞（包括难治性前列腺癌细胞）通过自噬机制给予细胞死亡的指示。 还公开了与目前公开的方法相关的药物组合物。