
AMG-706 (Motesanib) is an orally-available, nicotinamide-based, ATP-competitive inhibitor of the VEGFR family of kinases, KIT, and PDGFR with IC50s of 2, 3, and 6 nM, 8 nM, and 84 nM(for VEGFR1, VEGFR2, and VEGFR3), respectively. Besides Ret activity (IC50 = 59 nM), AMG-706 is highly selective against other unrelated kinases, including Src and EGFR. [1] AMG-706 potently inhibits VEGF-induced proliferation of HUVECs with IC50 values of 10 nM. PDGF-induced proliferation and SCF-induced c-Kit phosphorylation was also inhibited at IC50 values of 207 and 37 nM, respectively.AMG-706 was shown to increase tumor response to radiation in UM-SCC1 and SCC-1483 xenografts of head and neck squamous cell carcinomas. [2]
Technical information:
Chemical Formula: | C22H23N5O.2H3PO4 | |
CAS #: | 453562-69-1 | |
Molecular Weight: | 569.44 | |
Purity: | >98% | |
Appearance: | White | |
Chemical Name: | 3-Pyridinecarboxamide, N-(2,3-dihydro-3,3-dimethyl-1H-indol-6-yl)-2-[(4-pyridinylmethyl)amino]- | |
Solubility: | Up to 100mM in DMSO | |
Synonyms: | AMG-706, AMG 706, AMG706, Motesanib |
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. | Polverino et al., AMG 706, an oral, multikinase inhibitor that selectively targets vascular endothelial growth factor, platelet-derived growth factor, and kit receptors, potently inhibits angiogenesis and induces regression in tumor xenografts. Cancer Res. 2006, 66, 8715-8721. Pubmed ID:16951187 |
2. | Kruser et al., Augmentation of radiation response by motesanib, a multikinase inhibitor that targets vascular endothelial growth factor receptors. Clin. Cancer Res. 2010, 16, 3639-3647. Pubmed ID:20507929 |
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。

