Uses
PU139 is a potent pan-histone acetyltransferase (HAT) inhibitor. PU139 blocks the HATs Gcn5, p300/CBP-associated factor (PCAF), CREB (cAMP response element-binding) protein (CBP) and p300 with IC50s of 8.39, 9.74, 2.49 and 5.35 μM, respectively[1][2].
Biological Activity
PU139 is a potent pan-histone acetyltransferase (HAT) inhibitor. PU139 blocks the HATs Gcn5, p300/CBP-associated factor (PCAF), CREB (cAMP response element-binding) protein (CBP) and p300 with IC50s of 8.39, 9.74, 2.49 and 5.35 μM, respectively[1][2].
PU139 inhibits cell growth with GI50s of <60 μM (A431, A549, A2780, HepG2, SW480, U-87 MG, HCT116 and SK-N-SH and MCF7 cells)[1].PU139 (0-100 μM; 24-72 hours) triggers caspase-independent cell death in the neuroblastoma cell line SK-N-SH[1].
PU139 (25 mg/kg; i.p.) synergizes with Doxorubicin used as a prototypic chemotherapeutic drug in growth inhibition[1].
in vivo
PU139 (25 mg/kg; i.p.) synergizes with Doxorubicin used as a prototypic chemotherapeutic drug in growth inhibition[1].
| Animal Model: | Male NMRI:nu/nu mice (Neuroblastoma xenografts)[1] |
| Dosage: | 25 mg/kg |
| Administration: | Intraperitoneally (PU139) with Dxorubicin at 8mg/kg i.v.; Administered on days 14 and 21 as a single dose of each compound or, for combination therapy; both drugs were administered successively within 1h. |
| Result: | Optimum growth inhibition following a single PU139 therapy was moderate, but significant as compared with the untreated group and confirmed the previous findings.
|
IC 50
GCN5: 8.39 μM (IC
50); CREBBP: 2.49 μM (IC
50); PCAF: 9.74 μM (IC
50); p300: 5.35 μM (IC
50)
References
[1]. Gajer JM, et al. Histone acetyltransferase inhibitors block neuroblastoma cell growth in vivo. Oncogenesis. 2015;4(2):e137. Published 2015 Feb 9.
[2]. Carneiro VC, et al. Epigenetic changes modulate schistosome egg formation and are a novel target for reducing transmission of schistosomiasis. PLoS Pathog. 2014;10(5):e1004116. Published 2014 May 8.
