Lenalidomide-13C5-15N-CC-5013-sup-13-sup-C-sub-5-sub-sup-15-sup-N-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemELenalidomide-13C5,15NCat.No.:HY-A0003S2Synonyms:CC-5013-13C5,15N分子式:C₈₁₃C₅H₁₃N₂₁₅NO₃分子量:265.22作用靶点:LigandsforE3Ligase;Apoptosis;MolecularGlues;Isotope-LabeledCompounds作用通路:PROTAC;Apoptosis;Others储存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性Lenalidomide-13C5,15N是15N和13C标记的Lenalidomide(HY-A0003)。Lenalidomide(CC-5013)是Thalidomide的衍生物，也是一种具有口服活性免疫调节剂，以分子胶的方式作用。Lenalidomide(CC-5013)是一种泛素E3连接酶cereblon(CRBN)的配体，可通过CRBN-CRL4泛素连接酶对两种淋巴转录因子IKZF1和IKZF3进行选择性泛素化和降解。Lenalidomide(CC-5013)特别地抑制成熟B细胞淋巴瘤(包括多发性骨髓瘤)的生长，并诱导T细胞释放白细胞介素-2(IL-2)[1][2]。体外研究Stableheavyisotopesofhydrogen,carbon,andotherelementshavebeenincorporatedintodrugmolecules,largelyastracersforquantitationduringthedrugdevelopmentprocess.Deuterationhasgainedattentionbecauseofitspotentialtoaffectthepharmacokineticandmetabolicprofilesofdrugs[1].LenalidomideispotentinstimulatingTcellproliferationandIFN-γandIL-2production.LenalidomidehasbeenshowntoinhibitproductionofproinflammatorycytokinesTNF-α,IL-1,IL-6,IL-12andelevatetheproductionofanti-inflammatorycytokineIL-10fromhumanPBMCs.LenalidomidedownregulatestheproductionofIL-6directlyandalsobyinhibitingmultiplemyeloma(MM)cellsandbonemarrowstromalcells(BMSC)interaction,whichaugmentstheapoptosisofmyelomacells[3].Dose-dependentinteractionwiththeCRBN-DDB1complexisobservedwithThalidomide,LenalidomideandPomalidomide,withIC50valuesof~30μM,~3μMand~3μM,respectively,ThesereducedCRBNexpressioncells(U266-CRBN60andU266-CRBN75)arelessresponsivethantheparentalcellstoantiproliferativeeffectsLenalidomideacrossadose-responserangeof0.01to10μM[4].Lenalidomide,athalidomideanalog,functionsasamoleculargluebetweenthehumanE3ubiquitinligasecereblonandCKIαisshowntoinducetheubiquitinationanddegradationofthiskinase,thuspresumablykillingleukemiccellsbyp53activation[6].体内研究ThetoxicityofLenalidomidedosesupto15,22.5,and45mg/kgviaIV,IP,andPOroutesofadministration.1/2 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemELimitedbysolubilityinourPBSdosingvehicle,thesemaximumachievableLenalidomidedosesarewelltoleratedwiththeexceptionofonemousedeath(offourtotaldosed)atthe15mg/kgIVdose.Notably,noothertoxicitiesareobservedinthestudyatIVdosesof15mg/kg(n=3)or10mg/kg(n=45)oratanyotherdoselevelthroughIV,IP,andPOroutes[5].REFERENCESNagashima,Takeyuki,etal.PHARMACEUTICALCOMPOSITIONCOMPRISINGBICYCLICNITROGEN-CONTAININGAROMATICHETEROCYCLICAMIDECOMPOUNDASACTIVEINGREDIENT.Patent.20170360780A1.OmranA,etal.EffectsofMRP8,LPS,andlenalidomideontheexpressionsofTNF-α,brain-enriched,andinflammation-relatedmicroRNAsintheprimaryastrocyteculture.ScientificWorldJournal.2013Sep21;2013:208309.MinzelW,etal.SmallMoleculesCo-targetingCKIαandtheTranscriptionalKinasesCDK7/9ControlAMLinPreclinicalModels.Cell.2018Sep20;175(1):171-185.e25.KrönkeJ,etal.LenalidomideinducesdegradationofIKZF1andIKZF3.Oncoimmunology.2014Jul3;3(7):e941742.Lopez-GironaA,etal.Cereblonisadirectproteintargetforimmunomodulatoryandantiproliferativeactivitiesoflenalidomideandpomalidomide.Leukemia.2012Nov;26(11):2326-35.RozewskiDM,etal.Pharmacokineticsandtissuedispositionoflenalidomideinmice.AAPSJ.2012Dec;14(4):872-82.KotlaV,etal.Mechanismofactionoflenalidomideinhematologicalmalignancies.JHematolOncol.2009Aug12;2:36.RussakEM,etal.ImpactofDeuteriumSubstitutiononthePharmacokineticsofPharmaceuticals.AnnPharmacother.2019Feb;53(2):211-216.McePdfHeightCaut