Scriptaid (GCK-1026; Scriptide)

In vitro activity: Scriptaid (6 μM) causes a >100-fold increase in histone acetylation in PANC-1 cell. Scriptaid (8 μM) has minimal effects (80% survival rate) on MDAMB-468 but is not fatal to PANC-1 cells. Independent of a positive transcription inducer, scriptaid increases the transcription of pCMVb, p6SBE-luc, and p6MBE-luc. Using viral (SV40 and CMV) or human (ubiquitin c, UB6) promoters, Scriptaid can induce high expression of p6MBE-luc, pCMVb, and pUB6/V5-LacZ. This is independent of the reporter gene product (luciferase versus b-gal), the type of promoter (viral versus cellular), or the integration status of the reporter construct.[1] Scriptaid causes oocytes from somatic cell nuclear transfer (SCNT) to develop at high rates to the blastocyst stage. At all concentrations (50, 100, 250, 500, and 2000 nM, respectively), full-term development (3.4, 4.2, 7.6, 6.8, and 4.1%) is permitted. With a dose-dependent effect that peaks at 250 nM, scriptaid enhances the long-term development of cloned B6D2F1 embryos. The key inbred mouse strains, including DBA/2, C57BL/6, C3H/He, and 129/Sv, can all be cloned thanks to Scriptaid. Cloned embryos treated with Scriptaid have higher levels of newly synthesized mRNA. An ICSI-fertilized embryo's ability to develop is unaffected by a 48-hour exposure to 250 nM Scriptaid.[2] At an IC50 of 39 nM, scriptaid suppresses the growth of T. gondii tachyzoites. The HS68 monolayers are totally shielded from T. gondii tachyzoite by scriptaid (0.225 μM).[3] Scriptaid, after 48 hours of treatment, inhibits the growth of ER negative cell lines, MDA-MB-231, MDA-MB-435, and Hs578t, with an IC50 of 0.5-1.0 μg/mL. One microgram per milliliter After 48 hours of scriptaid treatment, ER mRNA transcript can increase by up to 20,000 times and both acetylated H3 and H4 histone tail proteins accumulate.[4] Scriptaid exhibits minimal sensitivity on normal human endometrial epithelial cells, but it inhibits the growth and viability of the Ishikawa endometrial cancer cell line and the SK-OV-3 ovarian cancer cell line with IC50 values of 9 μM and 55 μM, respectively. Cultured for two days in the presence of Scriptaid, endometrial and ovarian cancer cells exhibit an accumulation in the G0/G1 phase (5 μM of Scriptaid) and G2/M phase (10 μM of Scriptaid) of the cell cycle, accompanied by a decrease in the proportion of those in the S phase. Scriptaid at a concentration of 10 μM causes 56.1% of Ishikawa cells to undergo apoptosis, resulting in a loss of mitochondrial membrane potential and a 50% and 20% reduction in cyclin A and bcl-2 levels, respectively.[5]