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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。
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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.
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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
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.
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Patent Agency Ranking
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
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.
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15.发明申请SELECTIVE EFFLUX INHIBITORS AND RELATED PHARMACEUTICAL COMPOSITIONS AND METHODS OF TREATMENT 审中-公开选择性抑制剂和相关药物组合物和治疗方法公开(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。
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16.发明授权Selective efflux inhibitors and related pharmaceutical compositions and methods of treatment 有权选择性外排抑制剂及相关药物组合物和治疗方法公开(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。
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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。
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18.发明申请NITRIC OXIDE/cGMP PATHWAY INHIBITION OF VLA-4 RELATED CELL ADHESION 审中-公开硝酸氧化酶/ cGMP途径抑制VLA-4相关细胞粘附公开(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。
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