BPA-B9 is a RXRα ligand and antagonist that targets the pRXRα-PLK1 interaction. BPA-B9 has excellent RXRα binding affinity (KD=39.29 ± 1.12 nM). BPA-B9 inhibits cancer cell proliferation/growth by inducing mitotic arrest and apoptosis.

Physicochemical Properties

Molecular Formula	C25H26N4O2
Molecular Weight	414.50
Appearance	Typically exists as solid at room temperature
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 Bcl-2 Mcl-1
ln Vitro	In MDA-MB-231 cells, BPA-B9 (0-250 nM, 24 h) causes apoptosis [1]. The G2/M phase of the A549 cell cycle is inhibited by BPA-B9 (0-125 nM, 12 h) [1]. A dose- and time-dependent rise in the expression of cleaved PARP and a dose-dependent decrease in the anti-apoptotic proteins Bcl-2 and Mcl-1 are caused by BPA-B9 (0-500 nM, 0-24 h) [1]. BPA-effect B9 on TNBC Against HCC1937, A549, H460, HepG2, and HeLa cells, the IC50 values were 0.561 μM, 0.201 μM, and HeLa cells, respectively. The cell line MDA-MB-231 shown remarkable anti-proliferative activity (IC50=16 ± 3 nM, SI > 3). 0.128, 0.077, and 0.253 μM[1].
ln Vivo	BPA-B9 (0–25 mg/kg, intraperitoneal injection, once day for 15 days straight) exhibits strong anti-tumor actions in the body with few side effects [1]. In comparison to XS-060 (HY-149085), BPA-B9 (25 mg/kg, intraperitoneally or orally, once) has superior pharmacokinetics [1].
Cell Assay	Apoptosis Analysis[1] Cell Types: MDA-MB-231 cells and A549 cells Tested Concentrations: 0, 31.25, 62.50, 125, and 250 nM Incubation Duration: 24 h Experimental Results: Induced a dose-dependent t(0, 31.25, 62.50, 125, and 250 nM) increase(7.96, 16.94, 28.30, 30.40, 40.40%) of apoptotic cells in MDA-MB-231 cells. Cell Cycle Analysis[1] Cell Types: MDA-MB-231 cells and A549 cells Tested Concentrations: 0, 15.625, 31.25, 62.50, and 125 nM Incubation Duration: 12 h Experimental Results: Inhibited the cell cycle of A549 in the G2/M phase. After incubation with BPA-B9 at 62.50 nM and 125 nM, the percentage of A549 cells in the G2/M phase reached 12.89% and 46.49%, respectively, compared to 8.62% in untreated cells. Western Blot Analysis[1] Cell Types: MDA-MB-231 cells Tested Concentrations: 0, 7.8, 31.3, 125, and 500 nM Incubation Duration: 0, 1, 3, 6, 8, 10, 12, 16, and 24 h Experimental Results: Induced a time-dependent increase in the expression of cleaved PARP. Moreover, cleaved PARP was elevated, and anti-apoptosis proteins Bcl -2 and Mcl-1 were decreased dose-depend
Animal Protocol	Animal/Disease Models: balb/c (Bagg ALBino) mouse (aged 4-6 weeks, with injection of MDA-MB-231 cells)[1] Doses: 0, 12.5, 25 mg/kg Route of Administration: IP, once every day for 15 days Experimental Results: Inhibited tumor growth by causing mitotic arrest, chromosome aberrations, and DNA-damage response. Dramatically decreased the tumor volume and the tumor growth inhibition (TGI) of BPA-B9 was 59.3% at a dosage of 25.0 mg/kg/day, but a slight difference was shown at the dose of 12.5 mg/kg/day with no statistical significance. Animal/Disease Models: SD (Sprague-Dawley) rats (10-14 weeks, 200-220g)[1] Doses: 25 mg/kg Route of Administration: Oral absorption (po ) and intraperitoneal (ip)injection, once, (pharmacokinetic/PK Analysis) Experimental Results: The oral absorption of BPA-B9 is very poor, while intraperitoneal (ip)injection displayed good absorption. pharmacokinetic/PK Parameters of XS-060 in SD (Sprague-Dawley) rats[1]. BPA -B9 25 mg/kg (ip) Tmax (h) 0.14 ± 0.10 Cmax (μg/L) 8083.33 ± 1193.04 AUC0-∞ (μg⋅h/L) 14615.65 ± 5508.77 T1/2 (h) 2.23 ± 0.17 CLz/F (L/(h⋅kg)) 1.55 ±
References	[1]. Discovery of bipyridine amide derivatives targeting pRXRα-PLK1 interaction for anticancer therapy. Eur J Med Chem. 2023 Apr 6;254:115341.

Solubility Data

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	2.4125 mL	12.0627 mL	24.1255 mL
	5 mM	0.4825 mL	2.4125 mL	4.8251 mL
	10 mM	0.2413 mL	1.2063 mL	2.4125 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.