pilaralisib (SAR245408)

Parsaclisib was detected by gradient elution on an Acquity UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) using acetonitrile and 0.1% formic acid as mobile phases, and pilaralisib was used as an internal standard (IS). Finally, in vitro results showed that parsaclisib had a slow intrinsic clearance (Clint) value of 2.4 µL/min/mg protein with a half-life (t1/2) value of 571.3 min. These findings theoretically supported the potential metabolism of parsaclisib in vivo.

Furthermore, anti-programmed cell death protein 1 immunotherapy strongly downregulated the expression of APOC1 in patients with ACC. Both pilaralisib and elesclomol strongly inhibited SW13 cell growth.ConclusionsThis study preliminarily clarified that APOC1 and APOE might be potential therapeutic and prognostic targets for ACC, and identified new targets and treatment strategies for ACC.

Aims To characterize functional responses to 10 PI3Ki in CLL To study PI3Ki drug class activity in idelalisib-refractory CLL To investigate whether ex vivo drug sensitivity can predict in vivo treatment responses Methods CLL cells from patients that were treatment naïve (n=7), idelalisib refractory (n=9), or on idelalisib treatment (longitudinal samples from n=6 patients) were screened against 10 PI3Ki (buparlisib, compound 7n, copanlisib, duvelisib, idelalisib, nemiralisib, pictilisib, pilaralisib, umbralisib, ZSTK474), both alone and in combination with the B-cell lymphoma 2 (Bcl-2) antagonist venetoclax...Ex vivo drug testing on CLL cells from a patient who presented with relapsed disease after sequential treatment with FCR, ibrutinib, idelalisib and venetoclax revealed sensitivity to PI3Ki+venetoclax treatment...Conclusion Our findings indicate PI3Ki drug class activity in idelalisib-refractory CLL, and suggest that ex vivo drug sensitivity may guide precision medicine and predict treatment responses. These results warrant further testing in larger cohorts and in clinical trials.