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1. 发明申请

US20090246785A1 NOVEL STEROID 5-ALPHA-REDUCTASE 有权
标题翻译：新型甾体5-ALPHA-REDUCTASE
公开(公告)号：US20090246785A1
公开(公告)日：2009-10-01
申请号：US12404590
申请日：2009-03-16
申请人： James L. Mohler , Mark Titus , Olga Kozyreva , O. Harris Ford, III , Elsbieta Kawinski , Yun Li
发明人： James L. Mohler , Mark Titus , Olga Kozyreva , O. Harris Ford, III , Elsbieta Kawinski , Yun Li
IPC分类号： C12Q1/68 , C12Q1/26
CPC分类号： C12Q1/26 , C07K2319/21 , C07K2319/40 , C12N9/001 , C12N2799/022 , G01N33/57434
摘要： The invention provides an isolated, novel steroid 5α-reductase enzyme termed SRD5AIII. The protein has an estimated molecular weight of 37 kDa and is capable of converting testosterone to dihydrotestosterone at a pH of about 7.0. Also provided is a method for identifying inhibitors of SRD5AIII by contacting SRD5AIII with a test compound and measuring the activity of the enzyme. A reduced activity relative to a control indicates that the test compound is an inhibitor of SRD5AIII. A method is also provided for detecting androgen stimulated prostate cancer or recurrent prostate cancer in an individual. The method comprises obtaining a prostate biopsy from an individual and determining the level of expression of SRD5AIII gene or protein relative to a normal control. An increased expression of SRD5AIII relative to the control is indicative of androgen stimulated prostate cancer or recurrent prostate cancer.
摘要翻译：本发明提供了一种分离的新型类固醇5α-还原酶，称为SRD5AIII。蛋白质具有37kDa的估计分子量，并且能够在约7.0的pH下将睾酮转化为二氢睾酮。还提供了通过使SRD5AIII与测试化合物接触并测量酶的活性来鉴定SRD5AIII的抑制剂的方法。相对于对照的降低的活性表明测试化合物是SRD5AIII的抑制剂。还提供了用于检测个体中激素刺激的前列腺癌或复发性前列腺癌的方法。该方法包括从个体获得前列腺活检，并确定相对于正常对照的SRD5AIII基因或蛋白质的表达水平。 SRD5AIII相对于对照的增加的表达指示雄激素刺激的前列腺癌或复发性前列腺癌。

2. 发明授权

US08241845B2 Steroid 5α-reductase 有权
标题翻译：类固醇5α-还原酶
公开(公告)号：US08241845B2
公开(公告)日：2012-08-14
申请号：US12404590
申请日：2009-03-16
申请人： James L. Mohler , Mark Titus , Olga Kozyreva , O. Harris Ford, III , Elsbieta Kawinski , Yun Li
发明人： James L. Mohler , Mark Titus , Olga Kozyreva , O. Harris Ford, III , Elsbieta Kawinski , Yun Li
IPC分类号： C12Q1/68 , C12Q1/26 , C12N15/53 , C12N9/02
CPC分类号： C12Q1/26 , C07K2319/21 , C07K2319/40 , C12N9/001 , C12N2799/022 , G01N33/57434
摘要： The invention provides an isolated, novel steroid 5α-reductase enzyme termed SRD5AIII. The protein has an estimated molecular weight of 37 kDa and is capable of converting testosterone to dihydrotestosterone at a pH of about 7.0. Also provided is a method for identifying inhibitors of SRD5AIII by contacting SRD5AIII with a test compound and measuring the activity of the enzyme. A reduced activity relative to a control indicates that the test compound is an inhibitor of SRD5AIII. A method is also provided for detecting androgen stimulated prostate cancer or recurrent prostate cancer in an individual. The method comprises obtaining a prostate biopsy from an individual and determining the level of expression of SRD5AIII gene or protein relative to a normal control. An increased expression of SRD5AIII relative to the control is indicative of androgen stimulated prostate cancer or recurrent prostate cancer.
摘要翻译：本发明提供了一种分离的新型类固醇5α-还原酶，称为SRD5AIII。蛋白质具有37kDa的估计分子量，并且能够在约7.0的pH下将睾酮转化为二氢睾酮。还提供了通过使SRD5AIII与测试化合物接触并测量酶的活性来鉴定SRD5AIII的抑制剂的方法。相对于对照的降低的活性表明测试化合物是SRD5AIII的抑制剂。还提供了用于检测个体中激素刺激的前列腺癌或复发性前列腺癌的方法。该方法包括从个体获得前列腺活检，并确定相对于正常对照的SRD5AIII基因或蛋白质的表达水平。 SRD5AIII相对于对照的增加的表达指示雄激素刺激的前列腺癌或复发性前列腺癌。

3. 发明申请

US20080176269A1 Method for determination of DHT levels in tissue samples 审中-公开
标题翻译：测定组织样品中DHT水平的方法
公开(公告)号：US20080176269A1
公开(公告)日：2008-07-24
申请号：US11973127
申请日：2007-10-08
申请人： James L. Mohler , Mark Titus , Kenneth Tomer
发明人： James L. Mohler , Mark Titus , Kenneth Tomer
IPC分类号： C12Q1/02 , G01N33/92
CPC分类号： G01N33/743 , G01N30/724
摘要： Provided is a method for determining the presence or amount of 5-α-dihydro-3-keto steroids (ADKSs) comprising the steps of preparing a sample for chromatographic separation, subjecting the sample to chromatographic separation, subjecting the chromatographically separated sample to atmospheric pressure photoionization (APPI), and detecting the amount of alkylated parent ions using mass spectrometry or methylated daughter ions by mass spectrometry after collisionally induced dissociation of the alkylated parent ions. Tandem mass spectrometry of ADKSs with a 6-member A ring and a 3-keto group using APPI and methanol as the alkoxy donor will produce methylated daughter ions with a mass/charge ratio of 85.0. Quantitation of this alkylated daughter ion provides a method to detect very low levels of ADKSs such as DHT. This method can also be used for the simultaneous detection of ADKSs and non-ADKSs.
摘要翻译：提供了一种用于确定5-α-二氢-3-酮类固醇（ADKS）的存在或量的方法，包括以下步骤：准备用于色谱分离的样品，使样品进行色谱分离，使色谱分离的样品经受大气压光电离（APPI），并且在碰撞诱导的烷基化母体离子解离之后通过质谱法检测使用质谱法或甲基化子离子的烷基化亲本离子的量。使用APPI和甲醇作为烷氧基供体的具有6个成员的A环和3个酮基的ADKS的串联质谱法将产生质量/电荷比为85.0的甲基化的子离子。这种烷基化的子离子的定量提供了检测非常低水平的ADKS如DHT的方法。该方法也可用于同时检测ADKS和非ADKS。

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