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：US09763967B2

公开(公告)日：2017-09-19

申请号：US14561787

申请日：2014-12-05

Applicant: Ball State Innovation Corporation ,  STC.UNM

Inventor： Susan A. McDowell ,  Robert E. Sammelson ,  Larry A. Sklar ,  Mark K. Haynes

IPC: A61K31/415 ,  A61K31/63 ,  A61K31/635

CPC classification number: A61K31/635

Abstract: The present disclosure relates to molecules which function as selective modulators (i.e., inhibitors and agonists) of the Ras-homologous (Rho) family of small GTPases and, in particular, CDC42 GTPase, and their use to treat bacterial infection including systemic infection from sources such as Staphylococcus aureus and Streptococcus pyogenes.

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：US10039771B2

公开(公告)日：2018-08-07

申请号：US15131358

申请日：2016-04-18

Applicant: STC.UNM

Inventor： Alexandre Chigaev ,  Larry A. Sklar ,  Dominique Perez

IPC: A61K35/12 ,  A61K31/58 ,  A61K31/47 ,  A61K31/122 ,  G01N33/50 ,  A61K31/4425 ,  A61K31/357 ,  A61K31/343 ,  A61K31/35 ,  A61K31/437 ,  A61K31/00 ,  A61K31/365 ,  A61K45/06

Abstract: In one embodiment, the invention provides a method of inhibiting cAMP efflux and increasing intracellular cAMP in a subject who suffers from, or who is at risk of developing, a cancer by administering to the subject a therapeutically-effective amount of a cAMP efflux inhibitor. Novel compounds, pharmaceutical compositions, diagnostics and screening methods are also provided.

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：US09677989B2

公开(公告)日：2017-06-13

申请号：US15006817

申请日：2016-01-26

Applicant: STC.UNM

Inventor： Larry A. Sklar ,  Bruce Edwards ,  Frederick Kuckuck

IPC: G01N15/14 ,  G01N35/08 ,  G01N21/64 ,  B01L3/00 ,  G01N35/00 ,  G01N35/10 ,  G01N15/00 ,  G01N15/10

CPC classification number: G01N15/1436 ,  B01L3/5085 ,  G01N15/1404 ,  G01N15/1459 ,  G01N21/6428 ,  G01N21/6486 ,  G01N35/0099 ,  G01N35/085 ,  G01N35/1095 ,  G01N2015/0065 ,  G01N2015/1006 ,  G01N2015/1402 ,  G01N2015/1413 ,  G01N2015/1477 ,  G01N2015/149 ,  G01N2021/6439 ,  G01N2201/06113 ,  Y10T436/117497 ,  Y10T436/118339 ,  Y10T436/119163 ,  Y10T436/2575

Abstract: The present invention, provides a flow cytometry apparatus for the detection of particles from a plurality of samples comprising: means for moving a plurality of samples comprising particles from a plurality of respective source wells into a fluid flow stream; means for introducing a separation gas between each of the plurality of samples in the fluid flow stream; and means for selectively analyzing each of the plurality of samples for the particles. The present invention also provides a flow cytometry method employing such an apparatus.

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。

公开(公告)号：US20140088034A1

公开(公告)日：2014-03-27

申请号：US14115170

申请日：2012-05-10

Applicant: STC.UNM

Inventor： Alexandre Chigaev ,  Larry A. Sklar

IPC: A61K31/708 ,  A61K31/132

CPC classification number: A61K31/708 ,  A61K31/132 ,  A61K31/506 ,  A61K31/655 ,  A61K31/665 ,  A61K45/06 ,  G01N33/5008 ,  G01N33/57488 ,  G01N2500/10 ,  G01N2800/50

Abstract: The invention provides methods of treating nitric oxide/cGMP pathway-cell adhesion disorders and related pharmaceutical compositions, diagnostics, screening techniques and kits. In one embodiment, the invention relates to a method for down-regulating α4β1-integrin affinity and inhibiting and reversing adhesion formation in patients or subjects in need using a nitric oxide donor.

Abstract translation: 本发明提供了治疗一氧化氮/ cGMP途径 - 细胞粘附病症和相关药物组合物，诊断，筛选技术和试剂盒的方法。 在一个实施方案中，本发明涉及一种下调α4和bgr1整合素亲和力并抑制和逆转使用一氧化氮供体的患者或需要受试者的粘连形成的方法。