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. Author manuscript; available in PMC: 2020 Jun 2.
Published in final edited form as: Nat Med. 2019 Dec 2;25(12):1938–1947. doi: 10.1038/s41591-019-0668-z

Extended Data Fig. 1. Expression of anti-apoptotic BCL-2 members and VHL in cancer, and the synthetic schemes of DT2216 and DT2216NC.

Extended Data Fig. 1

a, A representative of three immunoblot analyses of VHL in three different human tumor cell lines and platelets from three different individuals (indicated as units 1–3). b, Immunoblot analyses of the basal protein levels of BCL-XL, BCL-2, MCL-1 and VHL in different solid tumor cells. Data are a representative of two independent experiments. c, BCL2L1 and VHL mRNA expression (Log2 transformed) and mutational status were analyzed using TCGA PanCancer Atlas studies via cBioPortal. d, Synthetic schemes of DT2216, DT2216NC and VHL-L. Reagents and conditions: (i) (1) N-methylmorpholine, isobutyl chloroformate, THF, −25 °C then −15 °C; (2) NaBH4, H2O; (ii) Bu3P, diphenyl disulfide, toluene, 80 °C; (iii) DIBAL-H, toluene, −78 °C (iv) compound 5, NaBH(OAc)3, TEA, DCM; (v) TFA, DCM; (vi) TEA, acetonitrile, reflux; (vii) compound 10, EDCI, DMAP, DCM; (viii) Zn, HOAc, THF; (ix) HATU, TEA, DCM; (x) (1) LiOH monohydrate, MeOH, H2O; (2) compound 12, HATU, TEA, DCM; (xi) Ac2O, TEA, DCM.