- 生物活性
UNC0642是有效，选择性的赖氨酸甲基转移酶 G9a 和 GLP 抑制剂， 抑制 G9a 的IC50 值小于2.5 nM。
- 靶点
IC50: <2.5 nM (G9a)
- 体外研究
UNC0642 displays high
in vitro
and cellular potency, low cell toxicity, and excellent selectivity. UNC0642 is competitive with the peptide substrate and non-competitive with the cofactor SAM. The K
i
of UNC0642 is determined to be 3.7±1 nM. UNC0642 displays high
in vitro
potency for GLP (IC
50
< 2.5 nM), similar to G9a. UNC0642 is more than 300-fold selective for G9a and GLP over a broad range of kinases, GPCRs, transporters, and ion channels. UNC0642 exhibits high potency at reducing the H3K9me2 mark, low cell toxicity, and good separation of functional potency and cell toxicity in a number of cell lines. It reduces clonogenicity in PANC-1 cells, a pancreatic carcinoma cell line.
- 体内研究
A single intraperitoneal (IP) injection (5 mg/kg) of UNC0642 results in a plasma C
max
(maximum concentration) of 947 ng/mL and an AUC (area under the curve) of 1265 hr*ng/mL.
- 生物活性
5β-Dihydrocortisol，氢化可的松 (Cortisol) 的代谢产物，是潜在的盐皮质激素。5β-Dihydrocortisol 可以增强糖皮质激素的活性以提高眼压。5β-Dihydrocortisol 可引起乳腺癌细胞凋亡。
- 体外研究
5β-Dihydrocortisol (10-100 μM; 48 h) inhibits the viability of MCF-7 cells, with an IC
50
of 27.59 μM.
5β-Dihydrocortisol (14 μM; 24 h) induces 35.6% early apoptosis and 2.5% late apoptosis in MCF-7 cells.
5β-Dihydrocortisol (1-10 μM; 48 h) quenches the intrinsic fluorescence of human serum albumin (HAS) with a maximum emission peak at 360 nm, with no shift in fluorescence peak.
Cell Viability Assay
Cell Line:
MCF-7 and HEK 293 cells
Concentration:
10, 20, 40, 60, 80, 100 μM
Incubation Time:
48 hours
Result:
Inhibited the viability of MCF-7 cells in a dose-dependent manner.
No toxicity in terms of cell viability was observed with HEK293 cell line.
Apoptosis Analysis
Cell Line:
MCF-7 cells
Concentration:
14 μM
Incubation Time:
24 hours
Result:
Induced 35.6% and 2.5% of early and late apoptosis.
- 体内研究
5β-Dihydrocortisol (0.1-1.0%; 18 d) potentiates the action of topically applied Dexamethasone (0.06%) in raising the intraocular pressure (IOP) in young rabbits.
