Physicochemical Properties
| Molecular Formula | C25H18BRFN6O3 |
| Molecular Weight | 549.35 |
| CAS # | 3032451-66-1 |
| Appearance | White to off-white 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
| Targets | PARP-1 <0.001 nM (IC50) PARP-2 <0.001 nM (IC50) PARP3 1.1 nM (IC50) PARP4 1.0 nM (IC50) TNKS1 3.8 nM (EC50) TNKS2 12.4 nM (IC50) PARA6 9.5 nM (IC50) PARP-7 7.3 nM (IC50) ARTD10/PARP10 10.8 nM (IC50) PARA11 2.166 μM (IC50) human PARP12 14.1 nM (IC50) PARP14 35.914 μM (IC50) PARP15 51.623 nM (IC50) |
| ln Vitro | On Capan-1, Capan-1/OP, and Capan-1/TP cells, YCH1899 (7 days) exhibits strong anti-proliferative action with IC50 values of 0.10, 0.89, and 1.13 nM, respectively [1]. YCH1899 (0.001-1 nM, 4 h) suppresses PARP production while stabilizing the PARP1-DNA complex [1]. The growth of BRCA mutant/wild-type cells (V-C8, V79, HCT-15, and HCC1937) is inhibited by YCH1899 (3.5 h), with IC50s ranging from 1.19 to 44.24 nM[1]. Capan-1, Capan-1/OP, and Capan-1/TP cells are exposed to 1 μM of YCH1899 for 24 hours, which causes DNA damage and significantly increases the amount of γH2AX [1]. When administered at a concentration of 1 μM for 48 hours, YCH1899 significantly lowers the repair activity of homologous recombination (HR) in U2OS-DR-GFP cells [1]. |
| ln Vivo | In rats, YCH1899 (5 mg/kg, intravenously) exhibits a moderate capacity for scavenging [1]. In a tumor model derived from xenograft mice, YCH1899 in MDA-MB-436/OP (6.25, 12.5, and 25 mg/kg, given orally once daily for 27 days) and Capan-1/R (12.5 and 25 mg/kg, given orally once daily, lasting 21 days) overcome Talazoparib resistance and markedly decreased tumor volume [1]. |
| Cell Assay |
Cell Proliferation Assay[1] Cell Types: HCC1937, HCT-15, MDA-MB-436, UWB1.289, UWB1.289+BRCA1, V–C8, V79 cells Tested Concentrations: 0-1 μM approximately Incubation Duration: 24 h Experimental Results: Inhibited the proliferation of BRCA-Deficient/Wild-Type Cells and IC50s value were 4.54, 44.24, 0.52, 0.02, 0.34, 1.19, 29.32nM, respectively. Immunofluorescence[1] Cell Types: Capan-1, Capan-1/OP cells, Capan-1/TP cells Tested Concentrations: 0.01, 0.1, 1 μM Incubation Duration: 24 h Experimental Results: Increased γH2AX level in a dose-dependent manner. Western Blot Analysis[1] Cell Types: Capan-1 and Capan-1/ OP cells Tested Concentrations: 1, 10, 100 nM Incubation Duration: 4 h Experimental Results: Improved stability of PARP1-DNA complexes and induced chromatin-bound PARP1 accumulation in the presence of MMS(methanesulfonate). Inhibited PARP formation in the presence of 0.1% H2O2 . |
| Animal Protocol |
Animal/Disease Models: MDA-MB-436/OP xenografts and Capan-1/R-in vivo xenografts mice[1] Doses: 12.5 and 25 mg/kg Route of Administration: Oral administration Experimental Results: Inhibited MDA-MB-436/OP xenografts tumor growth with T/C of 36.74% and 15.29% at 12.5 and 25 mg/kg Inhibited Capan-1/R xenografts tumor growth with T/C of 48.92% and 13.87% at 12.5 and 25 mg/kg. Animal/Disease Models: rats[1 ] Doses: 5 mg/kg Route of Administration: intravenous (iv) injection Experimental Results: Had a moderate clearance rate (24.5 mL/min/kg) and half-life (3.25 h). |
| References |
[1]. YCH1899, a Highly Effective Phthalazin-1(2H)-one Derivative That Overcomes Resistance to Prior PARP Inhibitors. J Med Chem. 2023 Aug 21. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8203 mL | 9.1017 mL | 18.2033 mL | |
| 5 mM | 0.3641 mL | 1.8203 mL | 3.6407 mL | |
| 10 mM | 0.1820 mL | 0.9102 mL | 1.8203 mL |