PTC-028 is a potent and orally bioavailable compound that decreases BMI-1 levels by posttranslational modification. BMI-1, also known as a stem cell factor, is frequently upregulated in a number of cancers. Increased BMI-1 expression is associated with a poor prognosis, making it a promising therapeutic target in a variety of cancers, including ovarian cancer. Small-molecule inhibitors of BMI-1 are currently being developed due to its enormous pathologic significance. In clonal growth and viability assays, PTC-028 treatment preferentially inhibits cancer cells, while having no effect on normal cells. The mechanism by which PTC-028 causes the cellular BMI-1 to be depleted by hyperphosphorylation is what causes apoptosis to be caspase-dependent. This process is also accompanied by a temporal decrease in ATP and a compromised mitochondrial redox balance. In a mouse model of orthotopic ovarian cancer, PTC-028 taken orally as a single agent exhibits significant antitumor activity comparable to that of the conventional cisplatin/paclitaxel therapy. Therefore, PTC-028 has the potential to be used as an efficient therapeutic agent in patients with epithelial ovarian cancer who have few options for treatment.

Physicochemical Properties

Molecular Formula	C19H12F5N5
Molecular Weight	405.3241
Exact Mass	405.101
Elemental Analysis	C, 56.30; H, 2.98; F, 23.44; N, 17.28
CAS #	1782970-28-8
Related CAS #	1782970-28-8
PubChem CID	73427235
Appearance	White to off-white solid powder
LogP	4.7
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	3
Heavy Atom Count	29
Complexity	556
Defined Atom Stereocenter Count	0
InChi Key	JEZGPBWIZWPDHP-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H12F5N5/c1-10-26-15-6-13(20)14(21)7-16(15)29(10)18-9-25-8-17(28-18)27-12-4-2-11(3-5-12)19(22,23)24/h2-9H,1H3,(H,27,28)
Chemical Name	6-(5,6-difluoro-2-methylbenzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrazin-2-amine
Synonyms	PTC-028; PTC028; PTC 028
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	BMI-1
ln Vitro	PTC-028 is a substance that is orally bioavailable and lowers BMI-1 levels through posttranslational modification. In clonal growth and viability assays, PTC-028 treatment selectively inhibits cancer cells, whereas normal cells are unaffected. Caspase-dependent apoptosis is enhanced by PTC-028's hyperphosphorylation-mediated depletion of cellular BMI-1, which is accompanied by a temporal decrease in ATP and a compromised mitochondrial redox balance[1].
ln Vivo	In a mouse model of orthotopic ovarian cancer, PTC-028 taken orally as a single agent exhibits significant antitumor activity comparable to that of the conventional cisplatin/paclitaxel therapy. Total plasma AUC0-24h at doses of 10 mg/kg and 20 mg/kg, respectively, are 10.9 and 26.1 mg/h/mL after administration to CD-1 mice in a single oral dose, demonstrating dose-proportional pharmacokinetics. PTC-028 has a Cmax of 0.79 and 1.49 mg/mL at a dose of 10 and 20, respectively. One hour post-dose, plasma concentrations have reached their Cmax at both dose levels, and then they gradually start to decline[1].
Cell Assay	PTC-028 is administered to cells for 48 hours at the indicated concentrations, and then the MTS assay is used to determine the viability of the cells.
Animal Protocol	Preclinical model of ovarian cancer (NCr-nu mcie; 6 to 8 weeks old) 10 mg/kg and 20 mg/kg oral administration
References	[1]. Evaluating the Mechanism and Therapeutic Potential of PTC-028, a Novel Inhibitor of BMI-1 Function in Ovarian Cancer. Mol Cancer Ther. 2018 Jan;17(1):39-49.

Solubility Data

Solubility (In Vitro)

DMSO: 81~125 mg/mL (199.8~308.4 mM) Ethanol: ~17 mg/mL (~41.9 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.13 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.13 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		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

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.