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：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：US10183032B2

公开(公告)日：2019-01-22

申请号：US15691977

申请日：2017-08-31

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

Abstract: The present disclosure relates to molecules that 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：US20170112813A1

公开(公告)日：2017-04-27

申请号：US15287323

申请日：2016-10-06

Applicant: STC.UNM

Inventor： Vojo Deretic ,  Eliseo Castillo ,  Steven Bradfute ,  Larry A. Sklar

IPC: A61K31/436 ,  A61K31/136 ,  A61K31/12 ,  A61K31/4184

CPC classification number: A61K31/436 ,  A61K31/12 ,  A61K31/136 ,  A61K31/4184 ,  A61K31/4365 ,  A61K31/4535 ,  A61K31/472 ,  A61K31/473 ,  A61K31/517 ,  A61K31/519 ,  A61K31/522 ,  A61K31/54 ,  A61K31/546 ,  A61K31/5685 ,  A61K31/585 ,  A61K31/65 ,  C07K16/18 ,  G01N33/56972 ,  G01N33/6893 ,  G01N2333/9015

Abstract: The invention provides methods of treating autophagy mediated diseases and disorders and related pharmaceutical compositions, diagnostics, screening techniques and kits. In one embodiment, the invention provides a method of determining whether a subject suffers from, or is at risk of developing, and autophagy mediated disease state and/or condition by evaluating LC3 levels.

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：US20180021357A1

公开(公告)日：2018-01-25

申请号：US15691977

申请日：2017-08-31

Applicant: Ball State Innovation Corporation ,  STC.UNM

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

IPC: A61K31/635

CPC classification number: A61K31/635

Abstract: The present disclosure relates to molecules that 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：US20160228457A1

公开(公告)日：2016-08-11

申请号：US15131358

申请日：2016-04-18

Applicant: STC.UNM

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

IPC: A61K31/58 ,  A61K31/47 ,  A61K31/357 ,  A61K45/06 ,  A61K31/365

CPC classification number: A61K31/58 ,  A61K31/00 ,  A61K31/122 ,  A61K31/343 ,  A61K31/35 ,  A61K31/357 ,  A61K31/365 ,  A61K31/437 ,  A61K31/4425 ,  A61K31/47 ,  A61K45/06 ,  G01N33/5011 ,  G01N2500/10 ,  G01N2800/52

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.

Abstract translation: 在一个实施方案中，本发明提供了通过向受试者施用治疗有效量的cAMP外排抑制剂来抑制患有或有风险发展为癌症的受试者的cAMP外排和增加细胞内cAMP的方法。 还提供了新颖的化合物，药物组合物，诊断和筛选方法。

公开(公告)号：US09267892B2

公开(公告)日：2016-02-23

申请号：US14134754

申请日：2013-12-19

Applicant: STC.UNM

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

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

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.