Tarloxotinib-bromide-TH-4000-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETarloxotinib bromideCat. No.: HY-17632CAS No.: 1636180-98-7Synonyms: TH-4000分式: CHBrClNO分量: 681.77作靶点: EGFR作通路: JAK/STAT Signaling; Protein Tyrosine Kinase/RTK储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 mont

2、h溶解性数据体外实验 DMSO : 33 mg/mL (48.40 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.4668 mL 7.3339 mL 14.6677 mL5 mM 0.2934 mL 1.4668 mL 2.9335 mL10 mM 0.1467 mL 0.7334 mL 1.4668 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验 请根据您的实验动物和给药式选择适当的溶解案，配制

3、前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (3.67 mM); Clear solution1/2 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 Tarloxotinib bromide (TH-4000)EGF

4、R/HER2 的个不可逆抑制剂。IC50 & Target EGFR/HER2体外研究 To confirm the mechanism of action, Tarloxotinib bromide is shown to be metabolized efficiently underhypoxia using a panel of human NSCLC cell lines (rate of TKI release 0.4-2.1 nM/hr/106 cells), a processthat is inhibited by oxygen (TKI release 6 cells).

5、Cellular anti-proliferative and receptor phosphorylationassays demonstrate a 14-80 fold reduction of Tarloxotinib bromide activity relative to TKI. Using PC9 tumors,hyperbaric oxygen breathing suppresse release of TKI from Tarloxotinib bromide by 80% (538 vs 99 nM/kg;p 2.体内研究 A prototypic WT EGFR dr

6、iven xenograft model (A431) is used to benchmark Tarloxotinib bromide activityagainst each EGFR-TKI by “retrotranslation” of reported plasma exposure for each agent in human subjectsback to the xenograft model. Only treatment with clinically relevant doses and schedules of Tarloxotinibbromide is ass

7、ociated with tumor regression and durable inhibition of WT EGFR tumor phosphorylation.Consistent with these findings, Tarloxotinib bromide treatment can also regress the WT EGFR NSCLC tumormodels H125 and H1648, demonstrating Tarloxotinib bromide provides the necessary therapeutic index toinhibit WT

8、 EGFR in vivo 1.REFERENCES1. Shevan Silva, Abstract A67: Preclinical efficacy of tarloxotinib bromide (TH-4000), a hypoxia-activated EGFR/HER2 inhibitor: rationalefor clinical evaluation in EGFR mutant, T790M-negative NSCLC following progression on EGFR-TKI therapy. Abstracts: AACR-NCI-EORTCInternat

9、ional Conference: Molecular Targets and Cancer Therapeutics; November 5-9, 2015; Boston, MA.2. Adam V. Patterson, Abstract 5358: The hypoxia-activated EGFR-TKI TH-4000 overcomes erlotinib-resistance in preclinical NSCLCmodels at plasma levels achieved in a Phase 1 clinical trial. AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA.McePdfHeightCaution: Product has not been fully validated for me