CPI203 | BET bromodomain inhibitor

CPI203 (1446144-04-2), a JQ1 analog, is a potent and selective inhibitor of the BET bromodomain BRD4 (IC₅₀ = 26 nM).¹ It helps promote the maintenance of hematopoietic stem cells via repression of Myc expression.² CPI203 reversibly suppressed intestinal stem cell differentiation in a mouse model.³ It enhanced the expansion of human cord blood hematopoietic stem cells without losing cell viability.⁴ CPI203 displays synergistic antitumor activity with various agents including lenalidomide⁵, bortezomib⁶, and PARP inhibitors⁷.

Refences/Citations:

1. Devaiah et al. (2012), BRD4 is an atypical kinase that phosphorylates serine2 of the RNA polymerase II carboxy-terminal domain; Proc.  Nat. Acad. Sci. USA 109 6927
2. Knudsen et al. (2015), ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation; Genes Dev., 29 1915
3. Nakagawa et al. (2016), Selective and reversible suppression of intestinal stem cell differentiation by pharmacological inhibition of BET bromodomains; Sci. Rep. 6 20390
4. Hua et al. (2020), The BET inhibitor CPI203 promotes ex vivo expansion of cord blood long-term repopulating HSCs and megakaryocytes; Blood 136 2410
5. Diaz et al. (2017), The BET bromodomain inhibitor CPI203 improves lenalidomide and dexamethasone activity in in vitro and in vivo models of multiple myeloma by blockade of Ikaros and MYC signaling; Haematologica 102 1776
6. Siegel et al. (2015), Small molecule inhibitor screen identifies synergistic activity of the bromodomain inhibitor CPI203 and bortezomib in drug resistant myeloma; Oncotarget 6 18921
7. Lui et al. (2020), BET, SRC, and BCL2 family inhibitors are synergistic drug combinations with PARP inhibitors in ovarian cancer; EBioMedicine 60 102988