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.