Physicochemical Properties
| Molecular Formula | C38H33CLFN7O5S |
| Molecular Weight | 754.23 |
| Appearance | Solid powder |
| 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
| ln Vitro | Polθ/PARP-IN-1 (compound 25d) (0-80 µM; 3 days) showed antiproliferative activity against HCC1937, MDA-MB-436, HCT116, SW48, SKOV-3, and MCF-10A with IC50 values of 20.9, 2.7, 8.9, 2.9, 18.9, and >80 µM, respectively[1]. Polθ/PARP-IN-1 (compound 25d) (2 µM; 3 days) induced apoptosis and cell cycle arrest at the G2/M phase, leading to DNA damage[1]. Cell Proliferation Assay[1] Cell Line: HCC1937, MDA-MB-436, HCT116, SW48, SKOV-3, MCF-10A cells Concentration: 0-80 µM Incubation Time: 5 days Result: Showed antiproliferative activity with IC50s of 20.9, 2.7, 8.9, 2.9, 18.9, >80 µM for H CC1937, MDA-MB-436, HCT116, SW48, SKOV-3, MCF-10A cells, respectively. Apoptosis Analysis[1] Cell Line: MDA-MB-436 cells Concentration: 2 µM Incubation Time: 3 days Result: Induced apoptosis with a higher apoptosis rate (26.7%) and arrested cell cycle progression at the G2/M phase. |
| ln Vivo | Polθ/PARP-IN-1 (20, 40 mg/kg; ip; daily for 21 consecutive days) inhibits tumor growth in the MDA-MB-436 xenograft model [1]. |
| Animal Protocol |
Animal/Disease Models:18-20 g, Six-week-old female BALB/C nude mice (MDA-MB-436 xenograft model)[1] Doses: 20, 40 mg/kg Route of Administration: I.p.; daily for 21 consecutive days Experimental Results: Significantly inhibited the growth of MDA-MB-436 xenografts in a dose-dependent manner, exerted an optimal inhibitory potency with a tumor growth inhibition (TGI) rate of 54.4%, 74.7% at 20, 40 mg/kg, respectively. |
| References |
[1]. Discovery and Proof of Concept of Potent Dual Polθ/PARP Inhibitors for Efficient Treatment of Homologous Recombination-Deficient Tumors. J Med Chem. 2024 Feb 20. |
Solubility Data
| Solubility (In Vitro) | DMSO : 50 mg/mL (66.29 mM; with sonication (<60°C)) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.31 mM)(Saturation unknown) in 10% DMSO 40% PEG300 5% Tween-80 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, add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix well; then add 50 μL Tween-80 to the above system and mix well; then add 450 μL saline to make up 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: ≥ 2.5 mg/mL (3.31 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, add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3259 mL | 6.6293 mL | 13.2586 mL | |
| 5 mM | 0.2652 mL | 1.3259 mL | 2.6517 mL | |
| 10 mM | 0.1326 mL | 0.6629 mL | 1.3259 mL |