Figure 1.

Structural consequences of the conversion from Abi to D4A that occurs in both mice, and patients, and requires 3βHSD. a, Schematic of Abi conversion to D4A. * double bond and C3-position for substrates and products of 3βHSD. b, Abi is converted to D4A in vivo. Abi acetate was injected i.p. in 5 mice. Blood was collected 2h and 4h after injection. Serum concentrations of Abi and D4A were quantified by mass spectrometry and are represented as the percentage of the sum total of Abi + D4A. c, D4A is detectable in all patients (n = 12) with CRPC treated with Abi acetate. d, Representative mass spectrometry tracing of D4A and Abi from the serum of a patient treated with Abi acetate. e, 3βHSD1 is capable of converting Abi to D4A. LAPC4 cells overexpressing 3βHSD1 were treated with 10μM Abi (or [³H]-DHEA) for 24h. Abi, D4A (as a percentage of Abi + D4A), [³H]-DHEA and [³H]-DHEA metabolites (labeled metabolites), were separated by HPLC. Results are shown as mean (n = 3) ± s.d. with biological replicates. The experiment was repeated independently at least 3 times.