https://openworks.mdanderson.org/sumexp22/1075/thumbnail.jp

Finkenbine, Ben

Grindel, Brian

Millward, Steven

Uddin, Md Nassir

English

OpenWorks @ MD Anderson

Title of the Poster Presentation Goes HereAuthors of the Poster Presentation Goes HereInstitutional and/or Graduate School of Biomedical Sciences Affiliation Goes Here Comparison of the DrugsDrug Type EC50 Non-ENO1 D423EC50 ENO1 D423ENO1/D423 RatioDrug 1 506 42,973 84.91Drug 2 1,135 276,377 243.50Drug 3 1,640 45,336 27.64IBuVCY27 850 172,583 203.04Previous IBuVCY27 530 139,318 262.47HEX 1,842 627,605 340.72• Inhibiting the glycolytic gene ENO2 is a known target for the destruction of ENO1-deleted tumor cells such as Glioblastoma.• The current best drug for targeting ENO2 is IBuVCY27 derived from HEX.• Three drugs similar in structure to IBuVCY27 may prove more effective at inhibiting ENO2.Fig 3. Synthesis of Drug 1 using 2-Hydroxy-5-methyl benzyl alcohol.Fig 4. Synthesis of Drug 2 using 2-Hydroxy-5-methoxy benzyl alcohol.Fig 5. Synthesis of Drug 3 using 3,5-Di-tert-butyl-2-hydroxy benzyl alcohol.Fig 2. Synthesis of IBuVCY27 using 2-Hydroxy benzyl alcohol.Fig 1. Synthesis of the intermediate from HEX.IntroductionMethodsFig 6. Proton NMR of Drug 1. The peaks on the graph represent the hydrogen atoms from the structure. It is used to confirm the compound. Each drug was confirmed this way. ResultsFig 7. Results of drugs vs the normalized effect on ENO1 D423 control cells. Each point represents the different concentration of drug added to the cells. As the concentration increases the percentage of cells affected increases.1 10 1001000100001000001000000-50050100150VCY27(iBu)nM Drug%Fraction AffectedD423ENO1 D423IBuVCY27 Non-ENO1 D423NO1 D4231 10 1001000100001000001000000-50050100150MNU-3-9nM Drug%Fraction AffectedD423ENO1 D423Drug 2 Non-ENO1 D423ENO1 D4231 10 1001000100001000001000000-50050100150MNU-3-11nM Drug%Fraction AffectedD423ENO1 D423Drug 3 Non-ENO1 D423ENO1 D4231 10 1001000100001000001000000-50050100150MNU-3-7nM Drug%Fraction AffectedD423ENO1 D423Drug 1 Non-ENO1 D423ENO1 D423Fig 10. The EC50 Non-ENO1 D423, says which compounds requires the lowest concentration to affect the most cells.• Drugs 1, 2, and 3, were successfully made and confirmed• Drug 1, Drug 2, and IBuVCY27 appear the best compounds.• The next step would be testing the stability of these drugs and advance to testing in vivo with mice in order to find the best drug.Conclusion• 1R01 CA266187 (S.W.M.)• MDACC Startup Funds (S.W.M.) • 2022 University Outreach Summer Programs, University of Texas MD Anderson Cancer CenterAcknowledgements1 10 100 1000 10000 100000-50050100150D423nM drug% Fraction AffectedVCY27 controlIBuVCY27Non-ENO1 D423101001000100001000001000000-50050100ENO1 D423nM drug% Fraction AffectedVCY27 controlIBuVCY27E O1 D423Fig 8. Previous run of IBuVCY27.V 27 ControlI CY27V 27 ControlI CY27101 102 103 104 105 106 107-50050100150HEXnM HEX% Fraction Affected D423D423 ENO1Non-ENO1 D423ENO1 D423HEXFig 9. Results of an unaltered HEX run. For comparisons.References• Lin, YH., Satani, N., Hammoudi, N. et al. An enolase inhibitor for the targeted treatment of ENO1-deleted cancers. Nat Metab 2, 1413–1426 (2020). https://doi.org/10.1038/s42255-020-00313-3baabaccccefgeggefgBen Finkenbine, Md Nassir Uddin, Brian Grindel, and Steven MillwardCancer Systems Imaging, UT MD Anderson Cancer Center, 1515 Holcombe Blvd. Houston. TX 77030, USAInvestigation of Ph sphate Pro-Drug Led Inhibition of ENO2 in ENO1-Deleted Cells 

Investigation of Phosphate Pro-Drug Led Inhibition of ENO2 in ENO1-Deleted Cells

https://openworks.mdanderson.org/cgi/viewcontent.cgi?article=1075&context=sumexp22

Investigation of Phosphate Pro-Drug Led Inhibition of ENO2 in ENO1-Deleted Cells

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