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    Use of BUBR1 as a biomarker of drug response to furazanobenzimidazoles
    2.
    发明授权
    Use of BUBR1 as a biomarker of drug response to furazanobenzimidazoles 有权

    公开(公告)号：US09970938B2

    公开(公告)日：2018-05-15

    申请号：US15060998

    申请日：2016-03-04

    Applicant: Basilea Pharmaceutica AG

    Inventor： Heidi Alexandra Lane ,  Felix Bachmann ,  Madlaina Breuleux ,  Michael Boutros ,  Daniel Gilbert ,  Xian Zhang

    IPC: G01N33/574 ,  A61K31/4245 ,  G01N33/50 ,  A61K31/4439 ,  C12Q1/68

    CPC classification number: G01N33/57484 ,  A61K31/4245 ,  A61K31/4439 ,  C12Q1/6886 ,  C12Q2600/158 ,  G01N33/5011 ,  G01N33/5026 ,  G01N33/57496 ,  G01N2333/91205 ,  G01N2800/44 ,  G01N2800/52

    Abstract: Use of BUBR1 as a biomarker for predicting the response to a compound, preferably resistance of a disease such as cancer in a subject, wherein the compound is a compound of general formula I wherein R represents phenyl, thienyl or pyridinyl wherein phenyl is optionally substituted by one or two substituents independently selected from alkyl, halo-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, acyloxy-lower alkyl, phenyl, hydroxy, lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, phenyl-lower alkoxy, lower alkylcarbonyloxy, amino, monoalkylamino, dialkylamino, lower alkoxycarbonylamino, lower alkylcarbonylamino, substituted amino wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, carboxy, lower alkoxycarbonyl, cyano, halogen, and nitro; and wherein two adjacent substituents are methylenedioxy; and wherein pyridinyl is optionally substituted by lower alkoxy, amino or halogen; X represents a group C═Y, wherein Y stands for oxygen or nitrogen substituted by hydroxy or lower alkoxy; R1 represents hydrogen, lower alkylcarbonyl, hydroxy-lower alkyl or cyano-lower alkyl; R2, R3 and R6 represent hydrogen; R4 and R5, independently of each other, represent hydrogen, lower alkyl or lower alkoxy; or R4 and R5 together represent methylenedioxy; and pharmaceutically acceptable derivatives thereof; or wherein R represents phenyl or pyridinyl wherein phenyl is optionally substituted by one or two substituents independently selected from alkyl, halo-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, acyloxy-lower alkyl, phenyl, hydroxy, lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, phenyl-lower alkoxy, lower alkylcarbonyloxy, amino, monoalkylamino, dialkylamino, lower alkoxycarbonylamino, lower alkylcarbonylamino, substituted amino wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, carboxy, lower alkoxycarbonyl, formyl, cyano, halogen, and nitro; and wherein two adjacent substituents are methylenedioxy; and wherein pyridinyl is optionally substituted by lower alkoxy, amino or halogen; X represents oxygen; R1 represents hydrogen, lower alkylcarbonyl, hydroxy-lower alkyl or cyano-lower alkyl; R2, R3 and R6 represent hydrogen; R4 and R5, independently of each other, represent hydrogen, lower alkyl or lower alkoxy; or R4 and R5 together represent methylenedioxy; and pharmaceutically acceptable derivatives thereof. Methods of treatment of neoplastic and autoimmune diseases with these compounds are also disclosed.

    USE OF BUBR1 AS A BIOMARKER OF DRUG RESPONSE TO FURAZANOBENZIMIDAZOLES
    4.
    发明申请
    USE OF BUBR1 AS A BIOMARKER OF DRUG RESPONSE TO FURAZANOBENZIMIDAZOLES 有权
    使用BUBR1作为药物反应的生物标志物对呋喃巴比妥

    公开(公告)号：US20160320397A1

    公开(公告)日：2016-11-03

    申请号：US15060998

    申请日：2016-03-04

    Applicant: Basilea Pharmaceutica AG

    Inventor： Heidi Alexandra Lane ,  Felix Bachmann ,  Madlaina Breuleux ,  Michael Boutros ,  Daniel Gilbert ,  Xian Zhang

    IPC: G01N33/574 ,  A61K31/4439 ,  C12Q1/68 ,  A61K31/4245

    CPC classification number: G01N33/57484 ,  A61K31/4245 ,  A61K31/4439 ,  C12Q1/6886 ,  C12Q2600/158 ,  G01N33/5011 ,  G01N33/5026 ,  G01N33/57496 ,  G01N2333/91205 ,  G01N2800/44 ,  G01N2800/52

    Abstract: Use of BUBR1 as a biomarker for predicting the response to a compound, preferably resistance of a disease such as cancer in a subject, wherein the compound is a compound of general formula I wherein R represents phenyl, thienyl or pyridinyl wherein phenyl is optionally substituted by one or two substituents independently selected from alkyl, halo-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, acyloxy-lower alkyl, phenyl, hydroxy, lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, phenyl-lower alkoxy, lower alkylcarbonyloxy, amino, monoalkylamino, dialkylamino, lower alkoxycarbonylamino, lower alkylcarbonylamino, substituted amino wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, carboxy, lower alkoxycarbonyl, cyano, halogen, and nitro; and wherein two adjacent substituents are methylenedioxy; and wherein pyridinyl is optionally substituted by lower alkoxy, amino or halogen; X represents a group C═Y, wherein Y stands for oxygen or nitrogen substituted by hydroxy or lower alkoxy; R1 represents hydrogen, lower alkylcarbonyl, hydroxy-lower alkyl or cyano-lower alkyl; R2, R3 and R6 represent hydrogen; R4 and R5, independently of each other, represent hydrogen, lower alkyl or lower alkoxy; or R4 and R5 together represent methylenedioxy; and pharmaceutically acceptable derivatives thereof; or wherein R represents phenyl or pyridinyl wherein phenyl is optionally substituted by one or two substituents independently selected from alkyl, halo-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, acyloxy-lower alkyl, phenyl, hydroxy, lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, phenyl-lower alkoxy, lower alkylcarbonyloxy, amino, monoalkylamino, dialkylamino, lower alkoxycarbonylamino, lower alkylcarbonylamino, substituted amino wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, carboxy, lower alkoxycarbonyl, formyl, cyano, halogen, and nitro; and wherein two adjacent substituents are methylenedioxy; and wherein pyridinyl is optionally substituted by lower alkoxy, amino or halogen; X represents oxygen; R1 represents hydrogen, lower alkylcarbonyl, hydroxy-lower alkyl or cyano-lower alkyl; R2, R3 and R6 represent hydrogen; R4 and R5, independently of each other, represent hydrogen, lower alkyl or lower alkoxy; or R4 and R5 together represent methylenedioxy; and pharmaceutically acceptable derivatives thereof. Methods of treatment of neoplastic and autoimmune diseases with these compounds are also disclosed.

    METHODS AND SYSTEMS FOR PREDICTING DRUG-RESPONSE
    6.
    发明申请
    METHODS AND SYSTEMS FOR PREDICTING DRUG-RESPONSE 审中-公开
    预防药物反应的方法和系统

    公开(公告)号：US20150024409A1

    公开(公告)日：2015-01-22

    申请号：US14380064

    申请日：2013-02-21

    Applicant: Nahid Razi

    Inventor： Nahid Razi

    IPC: G01N33/574

    CPC classification number: C12Q1/025 ,  G01N33/57492 ,  G01N2333/42 ,  G01N2333/46 ,  G01N2333/705 ,  G01N2400/40 ,  G01N2800/44 ,  G01N2800/52

    Abstract: Disclosed herein are methods and systems for determining whether a cell is resistant to one or more drugs. Also, disclosed herein are methods and systems for monitoring the treatment of a cancer patient to determine whether the cancerous cells being treated are resistant to the treatment. Further, disclosed herein are methods and systems for predicting the responsiveness of a cell to a drug. Also, disclosed herein are methods and systems to determine the rate of the efficacy of a chemotherapeutic drug on a cancerous, neoplastic or damaged cells

    Abstract translation: 本文公开了用于确定细胞是否对一种或多种药物具有抗性的方法和系统。 此外，本文公开了用于监测癌症患者的治疗以确定被治疗的癌细胞是否耐受治疗的方法和系统。 此外，本文公开了用于预测细胞对药物的反应性的方法和系统。 此外，本文公开了确定化疗药物对癌，肿瘤或损伤细胞的功效的速率的方法和系统

    METHOD FOR SCREENING ANTI-CANCER DRUGS AND METHOD OF CANCER TREATMENT
    8.
    发明申请
    METHOD FOR SCREENING ANTI-CANCER DRUGS AND METHOD OF CANCER TREATMENT 审中-公开
    筛选抗癌药物的方法和癌症治疗方法

    公开(公告)号：US20140148482A1

    公开(公告)日：2014-05-29

    申请号：US14079949

    申请日：2013-11-14

    Applicant: National Taiwan University

    Inventor： Da-Liang Ou ,  Chung-Wai Shiau ,  Chiun Hsu

    IPC: G01N33/50

    CPC classification number: G01N33/57438 ,  G01N33/6872 ,  G01N2800/44

    Abstract: The present application provides a method for screening compounds for cancer treatment comprising treating cancer cells with a candidate compound for sufficient time for detectable expression of a gene selected from GADD45 family; and detecting the level of expression of the gene as compared to the level of expression in the absence of the candidate compound; wherein an increased level of expression in the presence of the candidate compound as compared to expression in the absence of the candidate compound indicates that the candidate compound acts as an inhibitor of the cancer cells. In some embodiments, the method can be used for screening compounds for treatment of sorafenib-resistant hepatocellular carcinoma. The present application further provides a method for treating hepatocellular carcinoma comprising administering to a subject having hepatocellular carcinoma a therapeutic effective amount of an agonist of GADD45 family.

    Abstract translation: 本申请提供了一种筛选用于癌症治疗的化合物的方法，包括用候选化合物治疗癌细胞足够的时间以检测表达选自GADD45家族的基因; 并且与不存在候选化合物的表达水平相比，检测基因的表达水平; 其中与不存在候选化合物时的候选化合物相比，在候选化合物存在下增加的表达水平表明候选化合物作为癌细胞的抑制剂起作用。 在一些实施方案中，该方法可用于筛选用于治疗索拉非尼抗性肝细胞癌的化合物。 本申请还提供了一种治疗肝细胞癌的方法，其包括向具有治疗有效量的GADD45家族的激动剂的患有肝细胞癌的受试者施用。

    High Throughput Screening for Antimicrobial Dosing Regimens
    9.
    发明申请
    High Throughput Screening for Antimicrobial Dosing Regimens 审中-公开
    高通量筛选抗微生物剂量方案

    公开(公告)号：US20140011762A1

    公开(公告)日：2014-01-09

    申请号：US13899876

    申请日：2013-05-22

    Applicant: Vincent H. Tam ,  Michael Nikolaou

    Inventor： Vincent H. Tam ,  Michael Nikolaou

    IPC: G06F19/12 ,  C12Q1/02

    CPC classification number: G16B5/00 ,  C12Q1/025 ,  G01N2500/10 ,  G01N2800/44 ,  Y02A90/26

    Abstract: Provided herein are methods and computer-implemented systems for using computer simulations to predict likelihood of a cell population associated with a pathophysiological condition acquiring resistance to a therapeutic agent, to screen for therapeutic agents effective to suppress acquisition of resistance within a cell population and to treat the pathophysiological conditions associated therewith. The computer simulation comprises at least an input/out system and a mathematical model, including operably linked equations, parameter values and constant values, of growth response over a period of time of a cell population in contact with an therapeutic agent. Also provide is a method for determining a best-fit mathematical model of adaptation of a microbial population to a therapeutic agent over time and using the model to simulate microbial population behavior to a therapeutic agent.

    Abstract translation: 本文提供的方法和计算机实现的系统用于使用计算机模拟来预测与获得对治疗剂的抗性的病理生理条件相关联的细胞群体的可能性，筛选有效抑制细胞群体内的抗性获得并治疗的治疗剂 与之相关的病理生理条件。 计算机模拟至少包括输入/​​输出系统和数学模型，包括在与治疗剂接触的细胞群体的时间段内的生长响应的可操作地连接的方程，参数值和恒定值。 还提供了一种用于确定微生物群体随时间推移向治疗剂适应的最佳拟合数学模型的方法，并且使用该模型来模拟对治疗剂的微生物群体行为。

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