FG-4592 is an orally-available isoquinoline-based inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase for the treatment of anemia and patients with chronic kidney disease. [1] Phase 2 studies indicate that oral administration of FG-4592 three times a week increased mean hemoglobin levels in the first eight weeks, regardless of supplementation with IV or oral iron, or no iron supplementation. FG-4592 is novel in that it allows integration of red blood cell production and efficient iron incorporation simultaneously. [1]Data from Phase 2 trials comparing with epoetin alpha indicate that treatment with FG-4592 alone results in a sustained reduction of total plasma cholesterol levels by an average of 20%, while no reduction was seen with epoetin alpha. [2, 3]In December, 2012, Fibrogen and Astellas Pharma announced the initiation of a Phase 3 clinical development program for the treatment of anemia associated with chronic kidney disease in patients not on dialysis and on dialysis. [4]
Technical information:
Chemical Formula: | C19H16N2O5 | |
CAS #: | 808118-40-3 | |
Molecular Weight: | 352.34 | |
Purity: | > 98% | |
Appearance: | Yellow | |
Chemical Name: | 2-(4-hydroxy-1-methyl-7-phenoxyisoquinoline-3-carboxamido)acetic acid | |
Solubility: | Up to 100 mM in DMSO | |
Synonyms: | FG-4592, FG4592, ASP1517 |
Shipping Condition: The product is shipped in a glass vial at ambient temperature.Storage condition: For longer shelf life, store solid powder at 4oC desiccated, or store DMSO solution at -20oC.
Reference:
1. | "Correction of anemia without IV iron supplementation in incident dialysis patients" Fibrogen press release, Nov. 5, 2012 |
2. | "FG-4592 and epoetin alpha in Phase II anemia study", Datamonitor Research Store, Nov. 11, 1012. |
3. | "Hemoglobin correction and maintenance in end-stage renal patients" Fibrogen press release, Nov. 5, 2012 |
4. | Fibrogen press release, Dec. 11, 2012 (Phase 3 announcement) |
Other Information:
Product Specification (pdf) MSDS (pdf) Certificate of Analysis is available upon request.
ebiomall.com
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1. 姜黄素是一个典型的HAT抑制剂。
2. 针对P300: 在大约10年前,Cole和他的同事设计出了一种p300/CBP抑制剂,发表在nature杂志上。
希望能帮到你,望采纳!
Vanderbilt-Ingram癌症中心的主任HalMoses博士和他的实验室研究人员,于1985年辨识出TGF-b,这种物质具有生长刺激物和生长抑制的作用。从那段时间之后,TGF-b在直肠、乳房和其他癌症中所扮演的角色便获得研究人员的广泛研究。
如今Vanderbilt-Ingram癌症中心的一组研究人员,发现了TGF-b矛盾的生物学作用之线索。他们的研究结果将发表于2003年12月的NationalAcademyofScience网络版,网址为www.pnas.org,这篇研究将于2003年12月稍后发表于纸本中。
TGF-b通常会抑制细胞生长,但是,很多实质性肿瘤会过度表现TGF-b,而使细胞不完全被抑制,事实上,有时候它们因为TGF-b的讯息使肿瘤细胞的生长比正常细胞更快。
TGF-b使用多种标记途径将它的指令送达细胞核心,已知大约有至少四条途径以上。研究人员去除一种特殊蛋白质组成的TGF-b标记:Rho-ROCK。细胞便不再受到抑制,而再度开始生长。
[信息来源:中国科技信息网站]
该试剂盒是一种时间分辨的荧光共振能量转移免疫分析,该反应是一个竞争免疫反应,即铕标的cAMP示踪复合物与体系中的cAMP竞争结合标有Alexa Fluor 647染料的cAMP抗体。铕标cAMP示踪复合物是通过Biotin标记的cAMP与铕标的抗生物素蛋白链菌素(streptavidin)与抗体的复合物紧密结合产生的。
当抗体结合到示踪剂上时,340nm的激发光激发铕标分子,导致能量转移到Alexa Fluor 647染料上,结果产生665nm的发射光。荧光的强度与样品中的cAMP含量成反比。
本试剂盒用于检测在GPCR激动剂刺激下活细胞或者细胞膜制备品产生的cAMP。对于偶联Gαs的受体,激动剂刺激导致665nm的荧光强度降低,而拮抗剂则可以逆转这一效应;对于偶联Gαi的受体,在激动剂刺激的同时用forskolin刺激cAMP产生,那么激动剂则抑制forskolin诱导的cAMP的生成,因此对照只给forskolin的细胞组可以通过665nm荧光强度的增加反应激动剂的效应。
该试剂盒的灵敏度很高,室温下反应在20h内是稳定的。本试剂盒适用于在384孔板中进行24μl的微量分析。
2.保存条件
避光2~4℃保存,过期时间见外包装。
3.盒内试剂
cAMP标准品:1管,1ml。(50μM)
生物素标记的cAMP(b-cAMP):1管,25μl。
铕标的抗生物素蛋白链菌素:1管,25μl。
荧光标记的cAMP抗体:1管,40μl。
检测缓冲液:1瓶,25ml。
4.需要自配的其他溶液
l Hank’s balanced salt solution (HBSS): NaCl 8.0g、CaCl2 0.14g、KCl 0.4g、 KH2PO4 0.06g、Na2HPO4?7H2O0.09g、MgCl2.6H2O0.10 g、MgSO4.7H2O0.10 g、NaHCO30.35g、葡萄糖1.0g,加H2O至 1000ml (用7.5%NaHCO调节PH值=7.4)
l Versene消化液(1L):EDTA 0.372 g,NaCl 8.0g,KCl 0.20 g,KH2PO40.20g,Na2HPO4 1.15 g,D-glucouse 0.2 g,pH 7.4
l HEPES缓冲液(1mol/L):取2.383gHEPES溶于10ml去离子水中。
l 7.5%BSA溶液:取0.75gBSA溶于10ml去离子水中
l 0.5M IBMX溶液:11.11mg IBMX溶于100μl DMSO中,-20℃冻存。
l 刺激缓冲液(SB):14 ml HBSS(1×)+75μlHEPES(1mol/L)+200μlBSA (7.5%)。(注:在测定细胞cAMP时,反应缓冲液中要加入IBMX 0.5mmol/L)
l 吗啡贮存液(10mM):盐酸吗啡37.585mg溶于10ml生理盐水中,0.22μm滤膜过滤除菌,4℃保存备用。
l 纳络酮母液(100mM):纳络酮4mg溶于100μl 生理盐水中,用时工作液按照1:500稀释,溶剂为含有IBMX的反应缓冲液。
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MaggotsFasterThanScalpelinWoundDebridement
December19,2011—Maggotdebridementtherapy(MDT)appearstobemoreeffectiveforwounddebridementcomparedwithconventionaltherapy,butonlyat1week;afterthattime,anothertypeofdressingshouldbeused,newresearchsuggests.
KristinaOpletalovà,MD,fromtheDepartmentofDermatology,UniversityofCaen,France,andcolleaguespublishedonlineDecember19intheArchivesofDermatology.
MedicalmaggotswereapprovedbytheUSFoodandDrugAdmiNISTrationasamedicaldeviceforwounddebridementin2004.Accordingtotheresearchers,useofmaggotsintreatingwoundsisassociatedwitheffectivewounddebridement,antibacterialeffects,andstimulationofwoundhealing.
However,theypointout,"[r]elativelyfewclinicalstudieshavebeenconductedandtheresultsarenotclear,partlyowingtomethodologicassessmentproblems."
InthecurrentProspective,randomizedcontrolled,phase3clinicaltrial,theresearcherssoughttodeterminetheefficacyofbaggedlarvaeonwounddebridementincomparisonwithconventionaltreatment.
TheprimaryobjectivewastocomparethemeanpercentageofsloughinwoundstreatedwithMDTwiththatofconventionaltreatmentatday15.Thestudyincluded119patientswithanonhealing,sloughywoundthatwas40cm2orsmallerandlessthan2cmdeep.Patientsalsohadananklebrachialindexof0.8orhigher.
Treatmentwasadministeredduringa2-weekhospitalstay.Conventionaltreatmentconsistedofsurgicaldebridement3timesaweekwithascalpel,withuseoftopicalanesthesia.TheMDTwasadministeredusinganencloseddressing(Vitapad,BioMondeLaboratories)containing80sterilemaggots.Atdischarge,aconventionaldressingwasapplied,andpatientswerefollowed-upatday30.
DebridementbyMDTwassignificantlyfasterthansurgicaldebridementduringthefirstweekoftreatment,reachingthesamelevelthecontrolgroupreachedatday15.NobenefitforMDTcomparedwithconventionaltreatmentinhealingrateswasobserved.Atday8,54.5%intheMDTgroupvs66.5%inthecontrolgroup(P=.04)hadevidenceofsloughandwoundhealing.However,byday15,themeanpercentageofsloughwas55.4%intheMDTgroupand53.8%inthecontrolgroup(P=.78).
"AthoughMDTshowsnosignificantbenefitatday15comparedwithconventionaltreatment,debridementbyMDTissignificantlyfasterandoccursduringthefirstweekoftreatment,"theresearchersconclude."Becausethereisnobenefitincontinuingthetreatmentafter1week,anothertypeofdressingshouldbeusedafter2or3applicationsofMDT."
Painscoresweresimilarandmildinbothgroups,althoughincontrasttoconventionaltreatment,MDTwasperformedwithouttopicalanesthesia.
Accordingtotheresearchers,noneofthepatientswerereticentaboutundergoingMDT."[A]crawlingsensationonthewoundwasrarelyandalmostequallynotedinbothgroups,revealingthatthesensationwassubjective,"Dr.Opletalovàandcolleaguespointout.
TwoquestionsregardingMDTremainunanswered,theauthorsnote."Candebridementbeimprovedusingmoremaggotsperdressing?Ifso,wouldthesedressingsbemorepainful?Furtherstudiesareneededtoanswerthesequestions."
ThestudywassupportedbygrantsfromtheClinicalResearchHospitalProgramandfromtheFrenchSocietyofDermatology.Theauthorshavedisclosednorelevantfinancialrelationships.
ajtr0009-1230.pdf(2384.3k)
抑制剂刺激细胞后,需要用PBS清洗后再做后续实验吗