| Moniliformin (sodium salt)induces mitotic arrest at the metaphase stage |
Sample solution is provided at 25 µL, 10mM.
Nature.2017 Jan 19;541(7637):417-420.
Nature.2018 Nov;563(7731):407-411.Nature.2018 Jun 13.Nature.2018 Jun 27.Nature.2018 Mar 29;555(7698):673-677.Nature.2017 Sep 7;549(7670):96-100.Nature.2016 Apr 21;532(7599):398-401.
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Chemical structure
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| Cas No. | 71376-34-6 | SDF | Download SDF |
| Synonyms | N/A | ||
| Chemical Name | 3-hydroxy-3-cyclobutene-1,2-dione, monosodium salt | ||
| Canonical SMILES | O=C1C(C=C1[O-])=O.[Na+] | ||
| Formula | C4HO3 • Na | M.Wt | 120.0 |
| Solubility | ≤10mg/ml in H2O | Storage | Store at 4°C |
| Physical Appearance | A crystalline solid | Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
Moniliformin induces mitotic arrest at the metaphase stage.
Mitosis is a part of the cell cycle when replicated chromosomes are separated into two new nuclei. The process of mitosis is divided into stages corresponding to the completion of one set of activities and the start of the next.
In vitro: Moniliformin, first isolated as a mycotoxin from Fusarium moniliforme, was found to be phytotoxic and arrests mitosis of maize root meristematic cells at the metaphase stage. The mitotic spindle could be disrupted by the treatment of moniliformin, but no direct effect on tubulin had been observed [1].
In vivo: A previous study was conducted on rat heart to in situ determine the myocardial toxicity of moniliformin, originally isolated from mouldy corn and soil samples in the Keshan disease prevalent area in China. Results showed that perfusion of moniliformin 10-7 mol/liter in isolated heart decreased myocardial contractile force by 52%. Intravenous injection of moniliformin at 1/6 and 1/4 LD50 could markedly inhibit cardiac hemodynamic variables associated with myocardial contractile function. Moreover, moniliformin was able to decrease +/- LV dP/dt max by 52%, and induce ventricular arrhythmia. These findings indicated that moniliformin was toxic to mammalian heart and might be an important factor relative to Keshan disease [2].
Clinical trial: So far, no clinical study has been conducted.
References:[1] Duke, S. O. and Dayan, F.E. Modes of action of microbially-produced phytotoxins. Toxins (Basel) 3(8), 1038-1064 (2011).[2] Fan LL, Li J, Sun LH. Effect of moniliformin on myocardial contractility in rats. Biomed Environ Sci. 1991 Sep;4(3):290-4.
ebiomall.com
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名称：氨氧基乙酸盐;羧甲氧基胺半盐酸盐；
分子式：C2H5NO3·0.5HCl
分子质量：109.30
熔点：156℃
果糖胺是血浆中的蛋白质与葡萄糖非酶糖化过程中形成的高分子酮胺结构类似果糖胺的物质，它的浓度与血糖水平成正相关，并相对保持稳定。它的测定却不受血糖的影响。由于血浆蛋白的半衰期为17～20天，故果糖胺可以反映糖尿病患者检测前1～3周内的平均血糖水平。从一定程度上弥补了糖化血红蛋白不能反映较短时期内血糖浓度变化的不足。果糖胺的测定快速而价廉（化学法），是评价糖尿病控制情况的一个良好指标，尤其是对血糖波动较大的脆性糖尿病及妊娠糖尿病，了解其平均血糖水平有实际意义。但果糖胺不受每次进食的影响，所以不能用来直接指导每日胰岛素及口服降糖药的用量。血清果糖胺正常值为1.64～2.64mmol/L，血浆中果糖胺较血清低0.3mmol/L。
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FDAApprovesLenalidomideasMaintenanceTherapyforPatientsWithMultipleMyelomaFollowingAutologousStemCellTransplant
OnFebruary22,theU.S.FoodandDrugAdmiNISTration(FDA)expandedtheexistingindicationforlenalidomide(Revlimid)10mgcapsulestoincludeuseforpatientswithmultiplemyelomaasmaintenancetherapyfollowingautologoushematopoieticstemcelltransplant.TheexpandedindicationmakeslenalidomidethefirstandonlytreatmenttoreceiveFDAapprovalformaintenanceusefollowingautologoushematopoieticstemcelltransplant.
“Autologousstemcelltransplantafterinductiontherapyispartofthecontinuumofcarefortransplant-eligIBLe[patientswith]multiplemyeloma.However,mostpatientswillstillseetheirdiseaserecurorprogressafterthistreatment,”saidPhilipMcCarthy,MD,Director,BloodandMarrowTransplantCenter,DepartmentofMedicineatRoswellParkCancerInstitute.“Lenalidomidemaintenancetherapy,whichhasbeenshowntoincreaseprogression-freesurvivalfollowingautologousstemcelltransplantinclinicaltrials,canbeconsideredastandardofcareforthesepatients.”
ClinicalTrialFindings
Theapprovalwasbasedontwolargestudies—CALGB100104andIFM2005-02—includingmorethan1,000patientscomparinglenalidomidemaintenancetherapygivenuntildiseaseprogressionorunacceptabletoxicityafterautologoushematopoieticstemcelltransplantvsnomaintenance.Inbothstudies,theprimaryefficacyendpointwasprogression-freesurvival.
Inthemostcurrentprogression-freesurvivalanalysis,Study1(CALGB100104)demonstratedamedianprogression-freesurvivalof5.7years(95%confidenceinterval[CI]=4.4–notestimable)vs1.9years(95%CI=1.6–2.5)fornomaintenance,adifferenceof3.8years(hazardratio[HR]=0.38;95%CI=0.28–0.50).
Study2(IFM2005-02)alsoshowedabenefitwithamedianprogression-freesurvivalof3.9years(95%CI=3.3–4.7)vs2years(95%CI=1.8–2.3)fornomaintenance,adifferenceof1.9years(HR=0.53;95%CI=0.44–0.64).
Individualstudieswerenotpoweredforanoverallsurvivalendpoint.
AdescriptiveanalysisshowedthemedianoverallsurvivalinStudy1was9.3years(95%CI=8.5–notestimable)forpatientswhoreceivedlenalidomidevs7years(95%CI=5.9–8.6)fornomaintenance(HR=0.59;95%CI=0.4–0.78).InStudy2,medianoverallsurvivalwas8.8years(95%CI=7.4–notestimable)forpatientswhoreceivedlenalidomidevs7.3years(95%CI=6.7–9.0)fornomaintenance(HR=0.90;95%CI=0.72–1.13).
AdverseEvents
Themostfrequentlyreportedadversereactionsin≥20%(lenalidomidearm)acrossbothmaintenancestudies(Study1,Study2respectively)wereneutropenia(79%,61%);thrombocytopenia(72%,24%);leukopenia(23%,32%);anemia(21%,9%);upperrespiratorytractinfection(27%,11%);bronchitis(5%,47%);nasopharyngitis(2%,35%);cough(10%,27%);gastroenteritis(0%,23%);diarrhea(55%,39%);rash(32%,8%);fatigue(23%,11%);asthenia(0%,30%);musclespasm(0%,33%);andpyrexia(8%,21%).ThemostfrequentlyreportedGrade3or4reactions(morethan20%inthelenalidomidearm)includedneutropenia,thrombocytopenia,andleukopenia.
Thefrequenciesofonsetofadversereactionsweregenerallyhighestinthefirst6monthsoftreatmentandthenthefrequenciesdecreasedovertimeorremainedstablethroughouttreatment.
Inpatientsreceivinglenalidomidemaintenancetherapy,hematologicsecondprimarymalignanciesoccurredin7.5%ofpatientscomparedto3.3%inpatientsreceivingplacebo.Theincidenceofhematologicplussolidtumor(excludingsquamouscellcarcinomaandbasalcellcarcinoma)secondprimarymalignancieswas14.9%,comparedto8.8%inpatientsreceivingplacebowithamedianfollow-upof91.5months.Nonmelanomaskincancersecondprimarymalignancies,includingsquamouscellcarcinomaandbasalcellcarcinoma,occurredin3.9%ofpatientsreceivinglenalidomidemaintenance,comparedto2.6%intheplaceboarm.
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ICML2017:PhaseIIIbMAGNIFYStudyofLenalidomideandRituximabCombinationinRelapsed/RefractoryFollicularandMarginalZoneLymphoma
AninterimanalysisofMAGNIFY,aphaseIIIb,randomized,open-label,multicenterstudyoftheR2combinationregimen(lenalidomide[Revlimid]plusrituximab[Rituxan])inpatientswithrelapsedorrefractorymarginalzonelymphoma,waspresentedattheInternationalConferenceonMalignantLymphoma(ICML)inLugano,Switzerland.ThisanalysisexpandedupondatapresentedearlierinthemonthattheASCOAnnualMeeting(Abstract7502).
TheMAGNIFYstudycontinuestoevaluatetheclinicalactivityof12cyclesofR2combinationtherapyfollowedbyrandomizationtoeither18cyclesofR2maintenanceor18cyclesofrituximabmonotherapy,inpatientswithrelapsedorrefractoryfollicularlymphoma,marginalzonelymphoma,ormantlecelllymphoma.Approximately500patientsareplannedtobeenrolledinthestudy.
Theprimaryendpointisprogression-freesurvival.Secondaryendpointsincludeoverallsurvival,overallresponserate,completeresponse,improvementofresponse,durationofresponse,durationofcompleteresponse,timetonextlymphomatreatment,timetohistologictransformation,safety,andexploratoryquality-of-lifemeasures.EnrollmentintheMAGNIFYstudyisongoing.
ASCOData
AttheASCOAnnualMeeting,interimdatawerepresentedfromananalysisofasubsetofpatientsfromtheMAGNIFYstudywithrelapsedorrefractoryfollicularlymphoma(n=160)withearly-relapse(n=52)anddouble-refractory(n=50)disease.
AttheJanuary9,2017,datacutoff,the1-yearprogression-freesurvivalforallfollicularlymphomapatientswas70%,with65%fordouble-refractorypatientsand49%forearly-relapsepatients.Additionally,evaluablefollicularlymphomapatients(n=128)hadanoverallresponserateof66%withacompleteresponse/completeresponse–unconfirmedrateof38%.Fordouble-refractorypatients(n=42),overallresponseratewas45%withacompleteresponse/completeresponse–unconfirmedrateof21%andforearly-relapsepatients(n=43),overallresponseratewas47%withacompleteresponse/completeresponse–unconfirmedrateof21%.Mediandurationofresponsewasnotmetatamedianfollow-upof10.2months.
Themostcommongrade3or4adverseeventsobservedinthestudyforallfollicularlymphoma,double-refractory,andearly-relapsepatients,respectively,wereneutropenia(29%,42%,37%),fatigue(6%,4%,8%),leukopenia(5%,8%,10%),thrombocytopenia(4%,8%,4%),andlymphopenia(3%,6%,4%).
ICMLData
DatapresentedatICMLinaseparateanalysisfocusedonpatientswithmarginalzonelymphoma(n=38),includingnodalmarginalzonelymphoma(n=18),splenicmarginalzonelymphoma(n=10),andmucosa-associatedlymphoidtissuelymphoma(n=10).
Atamedianfollow-upof13.8monthsfrominitiationoftherapywiththeR2combination,evaluablepatientswithmarginalzonelymphoma(n=32)achievedanoverallresponserateof66%withacompleteresponse/completeresponse–unconfirmedrateof44%.Evaluablenodalmarginalzonelymphomapatients(n=14)hadanoverallresponserateof57%withacompleteresponse/completeresponse–unconfirmedrateof57%.Evaluablesplenicmarginalzonelymphomapatients(n=8)hadanoverallresponserateof63%withacompleteresponserateof25%;andevaluablemucosa-associatedlymphoidtissuelymphomapatients(n=10)hadanoverallresponserateof80%withacompleteresponse/completeresponse–unconfirmedrateof40%.Mediandurationofresponsewasnotreachedforanygroup.
Themostcommongrade3or4adverseeventsobservedinpatientswithmarginalzonelymphomawereneutropenia(32%),thrombocytopenia(16%),andleukopenia(11%).
“Thechemotherapy-freecombinationoflenalidomideandrituximab,withcomplementarymechanismsofactionthatarethoughttoenhanceantibodydependentcellularcytotoxicity,continuestoshowencouragingactivityandatolerablesafetyprofileinindolentlymphomas,andparticularlyindifficult-to-treatpatientsubsets,”saidDavidJ.Andorsky,MD,co–principalinvestigatorofthestudyandmedicaloncologistattheRockyMountainCancerCentersinBoulder,Colorado.“Theseresultsinpatientswhohadfailedmultipletherapiesorrelapsedearly,aswellastheactivityinmarginalzonepatientsmeritfurtherstudyinthisareaofindolentlymphoma.”
AboutMAGNIFY
MAGNIFYisaphaseIIIb,multicenter,open-labelstudyofpatientswithgrades1–3bortransformedfollicularlymphoma,marginalzonelymphoma,ormantlecelllymphomawhoreceivedatleast1priortherapyandhadstageI–IV,measurabledisease.Approximately500patientsareplannedforenrollmentin12cyclesofR2induction,withaprojected314patientswithatleaststablediseaseafterinductionrandomized(1:1)to2maintenancearms.
Inductionincludesorallenalidomideat20mg/d,days1–21per28-daycycle(d1–21/28)plusintravenousrituximabat375mg/m2,days1,8,15,and22ofcycle1andday1ofcycles3,5,7,9,and11(28-daycycles).Patientsarethenrandomizedtomaintenancelenalidomideat10mg/d,days1to21/28,cycles13to30,plusrituximabat375mg/m2,day1ofcycles13,15,17,19,21,23,25,27,and29(R2,armA),orrituximabalone(sameschedule,armB).PatientsreceivingR2maintenanceafter18cyclesmaycontinuemaintenancelenalidomidemonotherapyat10mg/d,days1–21/28(perpatientand/orinvestigatordiscretion),untildiseaseprogressionastolerated.Patientswillbefollowedfor≥5yearsafterthelastpatientinitiatesinductiontherapy.
如题，之前买的sigma的粉末，太贵。加培养基又不方便
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AdditionofIxazomibtoLenalidomide/DexamethasoneImprovesProgression-FreeSurvivalinRelapsed/RefractoryMultipleMyeloma
Moreauetalfoundthataddingtheoralproteasomeinhibitorixazomib(Ninlaro)tolenalidomide(Revlimid)anddexamethasonesignificantlyprolongedprogression-freesurvivalamongpatientswithrelapsed,refractory,orrelapsedandrefractorymultiplemyeloma.TheyreportedthefindingsfromthephaseIIITOURMALINE-MM1trialinTheNewEnglandJournalofMedicine.ThetrialsupportedtherecentU.S.FoodandDrugAdmiNISTration(FDA)approvalofixazomibinpreviouslytreatedmultiplemyeloma,makingitthefirstapprovedoralproteasomeinhibitor.
StudyDetails
Inthedouble-blindtrial,722patientsfrom147sitesin26countrieswererandomizedbetweenAugust2012andMay272014toreceiveixazomib(n=360)orplacebo(n=362)pluslenalidomideanddexamethasone.Treatmentconsistedof28-daycyclesoforalixazomibat4mgorplaceboondays1,8,and15;orallenalidomideat25mgondays1through21(10mginthosewithcreatinineclearance≤60or≤50mL/min/1.73m2accordingtolocalprescribinginformation);andoraldexamethasoneat40mgondays1,8,15,and22.Theprimaryendpointwasprogression-freesurvival.
Fortheixazomibvsplacebogroups,medianagewas66yearsinboth(53%vs51%>65years);58%vs56%weremale;86%vs83%werewhite;EasternCooperativeOncologyGroupperformancestatuswas0or1in95%vs93%;InternationalStagingSystem(ISS)stagewasIin63%vs64%,IIin25%vs24%,andIIIin12%inboth;78%vs72%hadcreatinineclearance≥60mL/min/1.73m2;55%vs60%hadstandard-and21%vs17%hadhigh-riskcytogenetics;numberofpriortherapieswas1in62%vs60%,2in27%vs31%,and3in11%vs9%;59%vs55%hadpriorstemcelltransplantation;diseasecategorywasrelapsedin77%inboth,refractoryin12%vs11%,relapsedandrefractoryin11%vs12%,andprimaryrefractoryin7%vs6%;priorproteasomeinhibitortherapywasbortezomib(Velcade)in69%inbothandcarfilzomib(Kyprolis)in<1%vs1%,with1%vs2%ofpatientshavingdiseaserefractorytopriortreatment;andpriorimmunomodulatorytherapywaslenalidomidein54%vs56%andthalidomide(Thalomid)in44%vs47%,with21%vs25%havingdiseaserefractorytopriortherapy.
ImprovedProgression-FreeSurvival
Aftermedianfollow-upof14.7months,medianprogression-freesurvivalwas20.6monthsintheixazomibgroupvs14.7monthsintheplacebogroup(hazardratio[HR]=0.74,P=.01).Benefitofixazomibwasconsistentacrossprespecifiedsubgroups,includingpoor-prognosissubgroupssuchasthosewithhigh-riskcytogenetics(24.1vs9.7months,HR=0.54),ISSstageIIIdisease(18.4vs10.1months,HR=0.72),thoseaged>75years(18.5vs13.1months,HR=0.87),andthosewhohadreceivedtwo(17.5vs14.1months,HR=0.75)orthree(notestimablevs10.2months,HR=0.37)priortherapies.
Overallresponserateswere78%vs72%,withtheratesofcompleteresponseplusverygoodpartialresponseof48%vs39%.Mediantimetoresponsewas1.1vs1.9months.Mediandurationofresponsewas20.5vs15.0months.Atmedianfollow-upofapproximately23months,medianoverallsurvivalhadnotbeenreachedineithergroup.
AdverseEvents
Adverseeventsof≥grade3occurredin74%oftheixazomibgroupvs69%oftheplacebogroup,withthemostcommonintheixazomibgroupbeingneutropenia(23%vs24%)andthrombocytopenia(19%vs9%).Rashofanygradewasmorecommonintheixazomibgroup(36%vs23%),asweregastrointestinaladverseevents(mostlylowgrade);22%ofixazomibpatientsand19%ofplacebopatientsreceivedantidiarrhealagents,and21%and13%receivedantiemeticdrugs.Peripheralneuropathyofanygradeoccurredin27%vs22%(grade3in2%ineach).
Seriousadverseeventsoccurredin47%vs49%.Adverseeventsledtodosereductionofanydrugin56%vs50%,discontinuationofanydrugin25%vs20%,anddiscontinuationofthestudyregimenin17%vs14%.Deathoccurredduringthestudyperiodin4%vs6%.
Theinvestigatorsconcluded:“Theadditionofixazomibtoaregimenoflenalidomideanddexamethasonewasassociatedwithsignificantlylongerprogression-freesurvival;theadditionaltoxiceffectswiththisall-oralregimenwerelimited.”
