Iberdomide

Iberdomide (CC-220) is an orally active and potent cereblon (CRBN) E3 ligase modulator (CELMoD) with an IC₅₀ of ~150 nM for cereblon-binding affinity. Iberdomide, a derivative of Thalidomide (HY-14658), has antitumor and immunostimulatory activities^[1][2]. In Vitro: Iberdomide (CC-220; 0.01, 0.1, 1, 10 μM; 72-96 hrs) has antiproliferative effects in a panel of multiple myeloma (MM) cell lines (EJM, H929, KMS11, KMS128M, KMS12PE, MM1.S, MM1.R, RPM-8226, U266 cells) across a range of concentrations^[1].
Iberdomide (0.1 μM; 96 hrs) induces apoptosis in all MM cell lines^[1].
Iberdomide (0.1 μM; 24, 48, 72 hrs) results in time-dependent increases in G0/G1 and sub-G1 cell cycle fractions on H929 cells^[1].
Iberdomide leads to rapid Aiolos depletion in the KMS12BM line^[1].
Iberdomide (0.1 μM) displays some anti-proliferative activity in two of the Pomalidomide-resistant (PR) lines with cereblon mutations (EJM/PR and H929/PR) along with decreased levels of cereblon protein^[1].
Iberdomide (0.1-1000 nM; 72 hrs) equally induces PBMC-mediated killing of both parental MM1.S cells and MM1.S/PR cells^[1].
In Vivo: Iberdomide (CC-220; 10 mg/kg; oral gavage) after 6 or 24 hours causes higher hCRBN expression in hC343 splenocytes correlated to deeper IKZF1/3 downregulation in WT (C57BL/6), hC123, or-343, (representing two different transgenic founder lines expressing hCRBN) and mCrbn^-/- mice^[2].