Asnuciclib

CDKI-73 (LS-007) is an orally active and highly efficacious CDK9 inhibitor, with K_i values of 4 nM, 4 nM and 3 nM for CDK9, CDK1 and CDK2, respectively. CDKI-73 down-regulates the RNAPII phosphorylation. CDKI-73 is also a novel pharmacological inhibitor of Rab11 cargo delivery and innate immune secretion^[1][2][3][4].
In Vitro: CDKI-73 is highly cytotoxic to primary leukemia cells derived from CLL patients (mean LD₅₀ = 0.08 μM) and shows>500-fold selectivity for primary leukemia cells over normal B-lymphocytes (LD₅₀ = 40.5 μM)^[1].
CDKI-73 (0.1 μM, 4 h) inhibits the phosphorylation of serine 2 of RNA polymerase II and MCL1 protein expression in CLL cells^[1].
CDKI-73 induced caspase-dependent apoptosis that was preceded by dephosphorylation of cdk9 and serine 2 of RNA polymerase II^[1].
CDKI-73 is highly effective against all cell lines tested with an IC₅₀ in the range of 0.012-0.517 μM; in particular three MLL-AML cell lines, namely MOLM13, MV4-11 and THP-1, were highly sensitive to CDKI-73 with IC₅₀ values <0.062 μM^[3].
In Vivo: CDKI-73 (25, 50, 100 mg/kg) markedly decreases tumor growth in a dose-dependent manner and results in a prolongation of animal life span (P < 0.001) without causing body weight loss and other overt toxicities.^[3].