Description:
IC50 Value: 1.7/5.0/1.8/2.8 nM (HDAC1/2/3/10); 19/54/39 nM (PI3Kα/β/δ) [1]
CUDC-907 potently inhibits class I PI3Ks as well as classes I and II HDAC enzymes.
in vitro: CUDC-907 induced the accumulation of acetylated histone H3, tubulin, and p53, as well as p21 expression in a dose-dependent manner (Supplementary Figs. S2-S5). Similarly, we observed that CUDC-907 inhibited the PI3K pathway, as indicated by the dose-dependent decreases in phosphorylation of AKT and its downstream targets, 4EBP-1 and p70S6, in H460 cells. CUDC-907 induced caspase-3 and -7 activation in HCT-116 colon cancer cells in a dose-dependent manner [1].
in vivo: oral administration of CUDC-907 inhibited growth of the Daudi cancer cell xenografts in a dose-dependent manner. Tumor stasis was observed at 100 mg/kg in this model without obvious toxicity. Furthermore, CUDC-907 caused tumor regression or stasis after intravenous (50 mg/kg) or oral administration (100 mg/kg) in a xenograft tumor model of SU-DHL4 diffuse large B-cell lymphoma (DLBCL) and caused tumor stasis in KRAS-mutant A549 NSCLC cell xenografts [1].
Toxicity: oral administration of CUDC-907 inhibited growth of the Daudi cancer cell xenografts in a dose-dependent manner. Tumor stasis was observed at 100 mg/kg in this model without obvious toxicity [1].
Clinical trial: Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of CUDC-907 in Patients With Lymphoma or Multiple Myeloma. Phase 1