PROTAC FLT3/CDKs degrader-1

PROTAC FLT3/CDKs degrader-1 (Compound C3) (0.03-500 nM; 0-36 h) potently degrades CDK2 in HL-60 cells, with a DC₅₀ of 18.73 nM. Degradation initiates at 12 h, and the agent acts via a ubiquitin-proteasome-dependent bivalent mechanism^[1].
PROTAC FLT3/CDKs degrader-1 (2 nM; unspecified concentration for DC₅₀ determination) selectively degrades CDK2/CDK4/CDK6/CDK9 and FLT3 (including FLT3^-ITD) in HL-60, MV4-11, KASUMI-1 and THP-1 human acute myeloid leukemia (AML) cells. It exhibits the strongest degradation activity against FLT3^-ITD in MV4-11 cells, and shows no significant effects on CDK1 or CDK5^[1].
PROTAC FLT3/CDKs degrader-1 (1-6.25 nM; 3-5 days) potently induces myeloid differentiation of HL-60 cells, with the proportion of CD11b-positive cells reaching 72.77% after treatment with 6.25 nM for 5 days^[1].
PROTAC FLT3/CDKs degrader-1 exhibits broad antiproliferative activity in human acute myeloid leukemia (AML) cell lines, with the highest potency in MV4-11 cells (IC₅₀ = 2.90 nM) and the lowest potency in THP-1 cells (IC₅₀ = 37.08 nM)^[1].
PROTAC FLT3/CDKs degrader-1 forms stable ternary complexes with CDK2 and CRBN through multiple specific intermolecular interactions, and also forms stable complexes with HPK1 and CRBN^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.