[CAS NO. 1782970-28-8] PTC-028
PRODUCTS SPECIFICATIONS [1782970-28-8]
DESCRIPTION [1782970-28-8]
Overview
| MDL | MFCD28716152 |
|---|---|
| Molecular Weight | 405.32 |
| Molecular Formula | C19H12F5N5 |
| SMILES | FC(C1=CC=C(NC2=NC(N3C4=CC(F)=C(F)C=C4N=C3C)=CN=C2)C=C1)(F)F |
Summary
IC50 & Target
BMI-1 [1]
In Vitro
PTC-028 (25-500 nM; 48 hours) significantly decreases CP20, OVCAR4 and OV90 epithelial ovarian cancer cells viability. However, in normal ovarian surface epithelial cells (OSE) and fallopian tube epithelial cells (FTE) cells, up to 500 nM treatment with PTC-028 for 48 hours has minimal effect (~18-30% decrease)
[1]
.
PTC-028 (100 nM; 2-12 hours) increases the phosphorylated BMI-1 species in a time-dependent manner. PTC-028 subsequently reduces BMI-1 in the biochemical functional readout
[1]
.
uH2A is observed up to 12 h with PTC-028 (100 nM) in both CP20 and OV90 cells while total H2A levels remain unchanged
[1]
.
PTC-028 (100 nM; 48 hours) decreases the expression of XIAP and RIPK1 while LC3B levels remains unchanged compared to that of the control
[1]
.
Significant cleavage of Caspase 7, Caspase 9 and PARP is observed in PTC-028 (100 nM; 48 hours)
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay [1]
| Cell Line: | OVCAR4, OV90 and CP20 cells |
| Concentration: | 0, 25, 50, 100, 200, 500 nM |
| Incubation Time: | 48 hours |
| Result: | OVCAR4, OV90 and CP20 cells demonstrated significant dose dependent decrease in cell viability with an IC 50 of ~100 nM and ~95% decrease at 500 nM. |
Western Blot Analysis [1]
| Cell Line: | OV90 and CP20 cells |
| Concentration: | 100 nM |
| Incubation Time: | 2, 4, 6, 12 hours |
| Result: |
A time-dependent increase in the phosphorylated BMI-1 species and subsequent reduction in the biochemical functional readout.
uH2A was observed up to 12 h while total H2A levels remained unchanged. |
In Vivo
PTC-028 (15 mg/kg; administered orally twice weekly) causes ~94% (0.169 g) reduction in tumor weight compared to the control (average tumor weight, ~3g)
[1]
.
No obvious toxicity is noted in the animals during therapy experiments as assessed by mean body weight
[1]
.
PTC-028 (10 mg/kg or 20mg/kg; single oral doses) is administrated to the CD-1 mice. The C
max
is reached at both dose levels 1h post dose after which plasma concentrations slowly reduce
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Female athymic nude mice with implanted OV90 cells [1] |
| Dosage: | 15 mg/kg |
| Administration: | Orally administered; twice weekly |
| Result: | Caused ~94% (0.169 g) reduction in tumor weight. |
| Animal Model: | Female CD-1 mice [1] |
| Dosage: | 10 mg/kg or 20mg/kg |
| Administration: | Oral administered; single dose |
| Result: | Total plasma AUC 0-24h were 10.9 and 26.1 μg•h/mL at doses of 10 and 20 mg/kg. The C max for PTC-028 at 10 and 20 mg/kg was 0.79 and 1.49 ug/mL, respectively. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 125 mg/mL ( 308.40 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.4672 mL | 12.3359 mL | 24.6719 mL |
| 5 mM | 0.4934 mL | 2.4672 mL | 4.9344 mL |
| 10 mM | 0.2467 mL | 1.2336 mL | 2.4672 mL |
-
1.
-
2.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.08 mg/mL (5.13 mM); Clear solution