公开(公告)号：US20180170897A1

公开(公告)日：2018-06-21

申请号：US15735840

申请日：2016-06-10

Applicant: STC.UNM ,  ROSALIND FRANKLIN UNIVERSITY

Inventor： Tudor I. Oprea ,  Cristian George Bologa ,  Oleg Ursu ,  Jun-Yong Choe ,  Cristina Iancu

IPC: C07D317/66 ,  A61K31/36 ,  A61K45/06 ,  C40B30/02 ,  A23L33/125

Abstract: The present invention relates to compounds which have been discovered to be potent ligands (inhibitors) of human GLUT5 (glucose transporter type 5), a facilitative glucose transporter that transports fructose, and their use as ligands assays which can uncover additional ligands of GLUT5, having the potential for being used as drugs. In addition, the present invention is directed to compounds, chemical compositions and methods for treating disease states and conditions which are mediated through GLUT5, including such disease states and conditions as GLUT5 deficiency syndrome, diabetes (type I and II), cancer, metabolic diseases including metabolic syndrome and fatty liver disease, among others.

公开(公告)号：US10822325B2

公开(公告)日：2020-11-03

申请号：US15735840

申请日：2016-06-10

Applicant: UNM RAINFOREST INNOVATIONS ,  ROSALIND FRANKLIN UNIVERSITY

Inventor： Tudor I. Oprea ,  Cristian George Bologa ,  Oleg Ursu ,  Jun-Yong Choe ,  Cristina Iancu

IPC: C07D317/66 ,  A61K31/36 ,  A61P3/10 ,  G16B35/00 ,  G16C20/60 ,  C07C317/36 ,  A23L33/125 ,  A61K45/06

Abstract: The present invention relates to compounds which have been discovered to be potent ligands (inhibitors) of human GLUT5 (glucose transporter type 5), a facilitative glucose transporter that transports fructose, and their use as ligands assays which can uncover additional ligands of GLUT5, having the potential for being used as drugs. In addition, the present invention is directed to compounds, chemical compositions and methods for treating disease states and conditions which are mediated through GLUT5, including such disease states and conditions as GLUT5 deficiency syndrome, diabetes (type I and II), cancer, metabolic diseases including metabolic syndrome and fatty liver disease, among others.

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：US20150087886A1

公开(公告)日：2015-03-26

申请号：US14510476

申请日：2014-10-09

Applicant: STC.UNM

Inventor： Robert Hromas ,  Andrei Leitao ,  Tudor I. Oprea ,  Larry A. Sklar ,  Elizabeth A. Williamson ,  Justin Wray ,  Wei Wang

IPC: C07D215/56 ,  C07D401/06 ,  A61K31/475 ,  A61N5/10 ,  C07D401/12 ,  A61K45/06 ,  C07D401/10 ,  A61K31/7048 ,  A61K31/47 ,  A61K31/496

CPC classification number: C07D215/56 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/475 ,  A61K31/496 ,  A61K31/7048 ,  A61K45/06 ,  A61N5/1001 ,  A61N5/1045 ,  A61N2005/1087 ,  A61N2005/1098 ,  C07D401/06 ,  C07D401/10 ,  C07D401/12 ,  A61K2300/00

Abstract: This invention relates to novel cancer treatment compositions and associated therapeutic methods. More particularly, this invention relates in part to small chemical bifunctional inhibitors of DNA replication and repair proteins Metnase and/or Intnase (also termed Gypsy Integrase, Gypsy Integrease-1, Gypsy Retransposon Integrase 1, or GIN-1) that simultaneously damage DNA, and to a therapeutic method that utilizes the inhibitors to increase the effectiveness of cancer treatment protocols, including radiation therapy.In preferred embodiments, compounds, compositions and methods of treatment of the invention are used to treat a patient suffering from leukemia (e.g. acute myeloid leukemia (AML) and related cancers. In certain aspects of such treatments, compounds, compositions and methods of treatment of the invention are administered as a monotherapy (in some cases, to patients who have exhibited resistance to Topo IIalpha inhibitors such as VP-16), or are co-administered with a Topo IIalpha inhibitor or other anti-cancer agents as otherwise described herein or in combination with radiation therapy.

Abstract translation: 本发明涉及新的癌症治疗组合物和相关的治疗方法。 更具体地说，本发明部分涉及同时损伤DNA的DNA复制和修复蛋白质Metnase和/或Intnase（也称为Gypsy整合酶，Gypsy Integrease-1，Gypsy Retransposon Integrase 1或GIN-1）的小型化学双功能抑制剂， 以及利用抑制剂增加包括放射治疗在内的癌症治疗方案的有效性的治疗方法。 在优选的实施方案中，本发明的化合物，组合物和治疗方法用于治疗患有白血病的患者（例如急性骨髓性白血病（AML）和相关的癌症）。在这些治疗的某些方面，化合物，组合物和治疗方法 本发明作为单一疗法（在某些情况下，对已显示出对Topo IIalpha抑制剂如VP-16具有抗性的患者）施用，或者与本文另有描述的Topo IIal抑制剂或其它抗癌剂共同施用，或 结合放射治疗。

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。