
AZD8055 is a potent and orally bioavailable ATP-competitive inhibitor of mTOR kinase with an IC50 of 0.8 nM. It inhibits both mTORC1 and mTORC2. AZD8055 shows excellent selectivity (1,000-fold) against all class I PI3K isoforms and other members of the PI3K-like kinase family. Furthermore, AZD8055 showed no significant activity against a panel of 260 kinases at concentrations up to 10 µM [1]. The serine/threonine kinase mTOR is crucial for cell growth and proliferation. It regulates cap-dependent translation through the mTORC1 complex and Akt activation through the mTORC2 complex. AZD8055 inhibits the phosphorylation of mTORC1 substrates p70S6K and 4E-BP1 as well as the phosphorylation of the mTORC2 substrate AKT. AZD8055 potently inhibits proliferation, induces autophagy and apoptosis in different cells. In vivo, AZD8055 induces a dose-dependent pharmacodynamic effect on phosphorylated S6 and phosphorylated AKT and results in significant tumor growth inhibition and/or regression in xenografts representing a broad range of tumor types [1-4].
Technical information:
Chemical Formula: | C25H31N5O4 | |
CAS #: | 1009298-09-2 | |
Molecular Weight: | 465.54 | |
Purity: | > 98% | |
Appearance: | White | |
Chemical Name: | (5-(2,4-bis((S)-3-methylmorpholino)pyrido[2,3-d]pyrimidin-7-yl)-2-methoxyphenyl)methanol | |
Solubility: | Up to 22 mM in DMSO | |
Synonyms: | AZD8055, AZD-8055 |
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. | Chresta CM, et al. AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity. Cancer Res. 2010. 70(1):288-98. Pubmed ID:20028854 |
2. | Sini P, et al. Simultaneous inhibition of mTORC1 and mTORC2 by mTOR kinase inhibitor AZD8055 induces autophagy and cell death in cancer cells. Autophagy. 2010. 6(4). Pubmed ID:20364113 |
3. | Willems L, et al. The dual mTORC1 and mTORC2 inhibitor AZD8055 has anti-tumor activity in acute myeloid leukemia. . Leukemia. 2012. 26(6):1195-202. Pubmed ID:22143671 |
4. | Naing A,et al. Safety, tolerability, pharmacokinetics and pharmacodynamics of AZD8055 in advanced solid tumours and lymphoma. Br J Cancer. 2012. 107(7):1093-9. Pubmed ID:22935583 |
Other Information:
Product Specification (pdf) MSDS (pdf) Certificate of Analysis is available upon request.
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RMgX + RX = R-R + MgX2.
这个反应需要的能量比生成格氏试剂的高,
因此降低反应温度是第一个选择。
其次, 增加镁得摩尔比, 让 RX与镁有更多机会反应, 而不是与RMgX。
第三, 降低RX的浓度, 即用更多的溶剂, 因为溶剂和格氏试剂有很显著的溶剂络合。
第四, 缓慢滴加RX., 即降低RX.在反应体系的浓度。
第五, 增加搅拌速率, 即, 让RX.与镁有更好的接触。
认领翻译的战友请跟帖注明“认领本文翻译,48小时内未完成,请其他站友认领”
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.
支原体培养则是取样后在培养基上培养,看有多少支原体菌落会长出,是比较直观和可信的结果。
总体来讲,这两种检查手段可信度都较高,结合一起,不仅可以可靠的知道有无解脲支原体感染,还能知道感染是否严重。

