| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| ln Vitro |
In MDA-MB-468 cells, PARP1/BRD4-IN-2 (compound BP44) can bind to BRD4 and PARP1 directly and increase their heat stability[1]. The antiproliferative effect of PARP1/BRD4-IN-2 is demonstrated against MDA-MB-231 and MDA-MB-468, with IC50 values of 3.01±0.83 μM and 6.61±0.58 μM, respectively[1]. In MDA-MB-468 cells, PARP1/BRD4-IN-2 (5, 10, and 20 μM) decreases colony formation and increases cell death by down-regulating Bcl-2, up-regulating Bax, and cleaving caspase-3 at 20 μM. DNA damage repair problems are caused by down-regulating Rad51 and p-RPA32, which is a dose-dependent way that PARP1/BRD4-IN-2 (5, 10, and 20 μM) down-regulates DNA damage-related proteins CtIP, Mre11, Rad51, and p-RPA32[1].
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|---|---|
| ln Vivo |
PARP1/BRD4-IN-2 (40 and 80 mg/kg; intragastric; for 16 days) significantly down-regulates the expression of CtIP, c-Myc, PAR, and Rad51 in tumor tissues and significantly inhibits tumor growth in xenograft mice without causing significant toxicities[1]. Sprague-Dawley rats' PARP1/BRD4-IN-2 pharmacokinetic parameters[1]. IV (1 mg/kg) PO (10 mg/kg) T1/2 (h) 3.02 ± 0.57 3.33 ± 0.71 Cmax (ng/mL) 258 ± 11 242 ± 6 AUC0-t (ng/mL·h) 629 ± 49 1489 ± 130 AUC0-∞ (ng/mL·h) 642 ± 36 1530 ± 146 VZ (L /kg) 21.1 ± 2.6 CL (mL/min/kg) 33.7 ± 1.5 F (%) 23.8 ± 1.3
|
| Animal Protocol |
Animal/Disease Models: Female BALB/c nude mice (implanted subcutaneously (sc) with MDA-MB-468 tumor cells)[1]
Doses: 40 and 80 mg/kg Route of Administration: IG, for 16 days Experimental Results: Dramatically inhibited tumor growth and exhibits no significant toxicities; and Dramatically down-regulated the expression of CtIP, c-Myc, PAR, and Rad51 in tumor tissues. |
| References |
| Molecular Formula |
C25H20N4O4
|
|---|---|
| Molecular Weight |
440.45
|
| Exact Mass |
440.148
|
| CAS # |
3037993-97-5
|
| PubChem CID |
164887499
|
| Appearance |
Typically exists as solid at room temperature
|
| Hydrogen Bond Donor Count |
2
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
33
|
| Complexity |
827
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
COC1=CC2=C(C(=C1)OC)C(=O)NC(=N2)C3=CC=CC(=C3)CC4=NNC(=O)C5=CC=CC=C54
|
| InChi Key |
VNFNYBBLPFNLBF-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C25H20N4O4/c1-32-16-12-20-22(21(13-16)33-2)25(31)27-23(26-20)15-7-5-6-14(10-15)11-19-17-8-3-4-9-18(17)24(30)29-28-19/h3-10,12-13H,11H2,1-2H3,(H,29,30)(H,26,27,31)
|
| Chemical Name |
5,7-dimethoxy-2-[3-[(4-oxo-3H-phthalazin-1-yl)methyl]phenyl]-3H-quinazolin-4-one
|
| 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)
|
| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2704 mL | 11.3520 mL | 22.7041 mL | |
| 5 mM | 0.4541 mL | 2.2704 mL | 4.5408 mL | |
| 10 mM | 0.2270 mL | 1.1352 mL | 2.2704 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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