Drug Discovery & Synthesis of Contraceptive Agents
Drug Discovery & Synthesis of Contraceptive Agents
批准号:
9107483
负责人:
Gunda I. Georg
金额:
$84.64万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2012
资助国家:
美国
项目状态:
已结题
起止时间:
2012-09-24 至 2017-06-30
关键词:
ActinsAdverse effectsAgonistAnimal ExperimentsAnimal TestingAnimalsBindingBioavailableBiological AssayBiological AvailabilityBundlingCalciumCationsChemicalsClinical TrialsCollaborationsContraceptive AgentsContraceptive methodsCouplesDevelopmentDrug DesignDrug KineticsEnzymesFemaleFemale Contraceptive AgentsFertilizationFundingGeneticGerm CellsGoalsGonadotropinsHealth SciencesHormonalHormonal Oral ContraceptivesHumanIn VitroInfertilityInstructionKansasKnock-outLeadMacacaMale Contraceptive AgentsMale InfertilityMarketingMedical centerMenstrual cycleMethodsModelingMusNational Institute of Child Health and Human DevelopmentNatural ProductsOocytesOralOregonPDE3A gene productPharmaceutical ChemistryPharmaceutical PreparationsPharmacologic SubstancePhosphotransferasesPregnancyPrimatesProdrugsPropertyRXRRegulationResearchResearch PersonnelRodentSpecificitySperm MotilityStructureUniversitiesVesicleWaterWomanWorkanalogbasecontraceptive targetdesigndrug discoverydrug synthesishigh throughput screeninghormonal contraceptionimprovedin vivoinhibitor/antagonistkinase inhibitorknock-downlarge scale productionmalemedical schoolsmennonhuman primatenoveloocyte maturationpreventprogramsretinoic acid receptor alphareversible contraceptivescaffoldscreeningsertoli cellsmall moleculesperm cellvirtual
中文摘要
三个男性和两个女性避孕药物的发现项目将进行,使用最先进的技术
英文摘要
Three male and two female contraceptive drug discovery projects will be pursued, using state-of-the-art
methods such as high throughput screening, structure-based drug design, and hit-to-lead optinnization by
medicinal chemistry: 1. H2-Gamendazole (H2-GMZ) and Analogues of Narciclasine (NAR) for Male
Contraception: The hypothesis of this project is that H2-GMZ and other small molecules such as NAR can
be developed as reversible non-hormonal anti-spermatogenic contraceptive agents that reversibly disrupt
eEFIA-actin bundling in Sertoli cells. 2. Retinoic Acid Receptor Alpha (RARalpha) as a Target for Male
Contraception: Knockout models of RARa (Rara"'") and animal experiments with a RAR pan-antagonist
have validated RARalpha as a viable target for establishing reversible male infertility. The discovery of an alpha-selective RAR antagonist with good oral bioavailability is expected to provide a male contraceptive agent that has fewer unwanted side effects than existing pan-antagonists. 3. CATSPER as a Target for Male Contraception: The Cation channel of Sperm (CatSper) is involved in the regulation of intracellular calcium, an important component required for the initiation of sperm hypermotility during mammalian fertilization. Our working hypothesis is that inhibitors of CatSper will reduce sperm hypermotility by preventing Ca2+ influx and rendering sperm unable to successfully penetrate and fertilize the oocyte. 4. WEE2 Kinase as a Target for Female Contraception: Knockdown of WEE2 prevents fertilization of mature primate oocytes, indicating that WEE2 represents a promising target for the development of non-hormonal, gamete-specific contraceptive for women. 5. PDE3A as a Target for Female Contraception: The principal catabolic enzyme in the oocyte is phosphodiesterase 3A (PDE3A). Pharmacologic inhibitors of PDE3A block oocyte maturation in many species, including primates. These observations have led to the hypothesis that a selective PDE3A inhibitor could be developed as a female contraceptive agent.
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DOI:
10.1021/cb500072z
发表时间:
2014-05-16
期刊:
ACS CHEMICAL BIOLOGY
影响因子:
4
作者:
[Ember, Stuart W. J., Zhu, Jin-Yi, Olesen, Sanne H., Martin, Mathew P., Becker, Andreas, Berndt, Norbert, Georg, Gunda I., Schoenbrunn, Ernst]
通讯作者:
Schoenbrunn, Ernst
DOI:
10.1158/1535-7163.mct-16-0568-t
发表时间:
2017-06
期刊:
Molecular cancer therapeutics
影响因子:
5.7
作者:
[Ember SW, Lambert QT, Berndt N, Gunawan S, Ayaz M, Tauro M, Zhu JY, Cranfill PJ, Greninger P, Lynch CC, Benes CH, Lawrence HR, Reuther GW, Lawrence NJ, Schönbrunn E]
通讯作者:
Schönbrunn E
DOI:
10.1002/cmdc.202000499
发表时间:
2022-08-03
期刊:
ChemMedChem
影响因子:
3.4
作者:
[]
通讯作者:
DOI:
10.1021/cb4003283
发表时间:
2013-11-15
期刊:
ACS CHEMICAL BIOLOGY
影响因子:
4
作者:
[Martin, Mathew P., Olesen, Sanne H., Georg, Gunda I., Schoenbrunn, Ernst]
通讯作者:
Schoenbrunn, Ernst
Scalable syntheses of the BET bromodomain inhibitor JQ1.
BET 溴结构域抑制剂 JQ1 的可扩展合成。
DOI:
10.1016/j.tetlet.2015.02.062
发表时间:
2015
期刊:
Tetrahedron letters
影响因子:
1.8
作者:
[Syeda,ShameemSultana, Jakkaraj,Sudhakar, Georg,GundaI]
通讯作者:
Georg,GundaI
Microbial Synthesis of Therapeutic Bile Acids for Alzheimer's Disease
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批准号:10602316
-
项目类别:
-
资助金额:$134.42万
-
财政年份:2020
-
负责人:Gunda I. Georg
-
依托单位:
Drug Discovery & Synthesis of Contraceptive Agents
-
批准号:8530619
-
项目类别:
-
资助金额:$88.84万
-
财政年份:2012
-
负责人:Gunda I. Georg
-
依托单位:
Drug Discovery & Synthesis of Contraceptive Agents
-
批准号:8700448
-
项目类别:
-
资助金额:$85.17万
-
财政年份:2012
-
负责人:Gunda I. Georg
-
依托单位:
Drug Discovery & Synthesis of Contraceptive Agents
-
批准号:8550538
-
项目类别:
-
资助金额:$84.14万
-
财政年份:2012
-
负责人:Gunda I. Georg
-
依托单位:
Drug Discovery & Synthesis of Contraceptive Agents
-
批准号:8551199
-
项目类别:
-
资助金额:$71.45万
-
财政年份:2012
-
负责人:Gunda I. Georg
-
依托单位:
Core - Drug, Discovery, Design and Synthesis
-
批准号:8152937
-
项目类别:
-
资助金额:$112.45万
-
财政年份:2010
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负责人:Gunda I. Georg
-
依托单位:
CORE--Drug, Discovery, Design and Synthesis
-
批准号:8066373
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项目类别:
-
资助金额:$44.28万
-
财政年份:2010
-
负责人:Gunda I. Georg
-
依托单位:
Libraries for HTS: Privileged Structures in Sparsely Populated Chemical Space
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批准号:7676007
-
项目类别:
-
资助金额:$46.96万
-
财政年份:2007
-
负责人:Gunda I. Georg
-
依托单位:
Libraries for HTS: Privileged Structures in Sparsely Populated Chemical Space
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批准号:7291334
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项目类别:
-
资助金额:$45.24万
-
财政年份:2007
-
负责人:Gunda I. Georg
-
依托单位:
Libraries for HTS: Privileged Structures in Sparsely Populated Chemical Space
-
批准号:7490019
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项目类别:
-
资助金额:$45.7万
-
财政年份:2007
-
负责人:Gunda I. Georg
-
依托单位:
COBRE: UKS: CORE C: MEDICINAL CHEMISTRY
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批准号:7381084
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项目类别:
-
资助金额:$34.48万
-
财政年份:2006
-
负责人:Gunda I. Georg
-
依托单位:
COBRE: UKS: CORE A: ADMINISTRATIVE CORE
-
批准号:7381082
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项目类别:
-
资助金额:$42.92万
-
财政年份:2006
-
负责人:Gunda I. Georg
-
依托单位:
CORE--FIRST AWARD & EQUIPMENT & FACILITY SUPPORT
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批准号:7170240
-
项目类别:
-
资助金额:$27.72万
-
财政年份:2005
-
负责人:Gunda I. Georg
-
依托单位:
COBRE: UKS: CORE A: ADMINISTRATIVE CORE
-
批准号:7170239
-
项目类别:
-
资助金额:$23.78万
-
财政年份:2005
-
负责人:Gunda I. Georg
-
依托单位:
CORE--MEDICINAL CHEMISTRY
-
批准号:7170242
-
项目类别:
-
资助金额:$29.96万
-
财政年份:2005
-
负责人:Gunda I. Georg
-
依托单位:
COBRE: UKS: CORE A: ADMINISTRATIVE CORE
-
批准号:7011656
-
项目类别:
-
资助金额:$24.92万
-
财政年份:2004
-
负责人:Gunda I. Georg
-
依托单位:
CORE--FIRST AWARD & EQUIPMENT & FACILITY SUPPORT
-
批准号:7011657
-
项目类别:
-
资助金额:$31.18万
-
财政年份:2004
-
负责人:Gunda I. Georg
-
依托单位:
COBRE: UKS: CORE D: MEDICINAL CHEMISTRY
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批准号:7011659
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项目类别:
-
资助金额:$22.56万
-
财政年份:2004
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负责人:Gunda I. Georg
-
依托单位:
Tyloindicines: Chemistry and Biology
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批准号:6438013
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项目类别:
-
资助金额:$29.14万
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财政年份:2002
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负责人:Gunda I. Georg
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依托单位:
Tyloindicines: Chemistry and Biology
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批准号:7003699
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项目类别:
-
资助金额:$31.61万
-
财政年份:2002
-
负责人:Gunda I. Georg
-
依托单位:
海外基金