Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemECXD101Cat.No.:HY-100748CASNo.:934828-12-3分?式:C??H??N?O分?量:403.52作?靶點(diǎn):HDAC作?通路:CellCycle/DNADamage;Epigenetics儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥31mg/mL(76.82mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.4782mL12.3910mL24.7819mL5mM0.4956mL2.4782mL4.9564mL10mM0.2478mL1.2391mL2.4782mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(6.20mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.20mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.20mM);ClearsolutionBIOLOGICALACTIVITY?物活性CXD101?種有效的，選擇性的，具有?服活性的I類HDAC抑制劑，對(duì)HDAC1，HDAC2和HDAC3的IC50分別為63nM，570nM和550nM。CXD101對(duì)II類HDAC沒有活性，并具有抗腫瘤活性。IC50&TargetHDAC1HDAC3HDAC263nM(IC50)550nM(IC50)570nM(IC50)體外研究CXD101hasbeentestedinvitroincolon,lung,non-Hodgkinlymphoma,andmyelomacelllineswithIC50srangedfrom0.2to15μM[2].體內(nèi)研究CXD101substantiallyreducestumorsizeinmurinexenograftlung(A549a)andcolon(HT29)modelsatadoseof50mg/kg.Tumorreductionsarefoundtobeassociatedwithincreasedhistoneacetylationand

decreasedHDACenzymeactivity[2].ForCXD101,afteroraldosinginmurineandcaninemodels,peakplasmaconcentrations(Cmax)arereached1to2hoursafterthedoseandterminalhalf‐livesare6hoursand8hours,respectively.Aftermurineoral[14C]-CXD101atadoseof1.6mg/kg(4μmol/kg),tissueradioactivitypeaked3to6hoursafterthedoseanddeclinedslowlythereafterwithCXD101‐relatedmaterialstillpresentintissue21daysafterthedose[2].REFERENCES[1].EyreTA,etal.Predictivebiomarkersfordiseasesensitivityinlymphoma-theholygrailforHDACinhibitors?Oncotarget.2018Dec18;9(99):37280-37281.[2].EyreTA,etal.Aphase1studytoassessthesafety,tolerability,andpharmacokineticsofCXD101inpatientswithadvancedcancer.Cancer.2019Jan1;125(1):99-108.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications