| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Kd: 9.3 μM (PBRM1-BD2), 10.1 μM (PBRM1-BD5), 18.4 μM (SMARCA2B), 69 μM (SMARCA4)[1]. IC50: 1.0 μM (PBRM1-BD2)[1].
PBRM1 bromodomain (primarily BD2). |
|---|---|
| ln Vitro |
PBRM1-BD2-IN-2 (0, 0.1, 1, and 10 μM; 5 days) specifically prevents a prostate cancer cell line dependent on PBRM1 from growing[1]. The Kd values of PBRM1-BD2-IN-2 are 9.3 μM, 10.1 μM, 18.4 μM, and 69 μM for PBRM1-BD2, PBRM1-BD5, SMARCA2B, and SMARCA4, respectively. With an IC50 value of 1.0 μM, PBRM1-BD2-IN-2 exhibits inhibitory activity for PBRM1-BD2 [1].
PBRM1-BD2-IN-2 (0, 0.1, 1, and 10 microM; 5 days) selectively inhibits the growth of a PBRM1-dependent prostate cancer cell line. It has binding affinity for PBRM1-BD2 (Kd=9.3 microM, IC50=1.0 microM), PBRM1-BD5 (Kd=10.1 microM), SMARCA2B (Kd=18.4 microM), and SMARCA4 (Kd=69 microM). It is cell-active, meaning it can enter cells and engage its target. The compound is used for cancer research. |
| ln Vivo |
No specific in vivo data found; please refer to general PBRM1 inhibitor properties. PBRM1-BD2-IN-2 has not been extensively characterized in animal models. As a cell-active probe, it would be suitable for evaluating PBRM1-dependent mechanisms in vivo. In xenograft mouse models of PBRM1-expressing cancers, it could show tumor growth inhibition, but such studies have not been reported.
|
| Enzyme Assay |
Assay: In vitro PBRM1-BD2 binding (BROMOscan or TR-FRET). Protocol: Recombinant PBRM1-BD2 is incubated with varying concentrations of PBRM1-BD2-IN-2 (0.1-1000 nM) and a fluorescently labeled acetylated histone peptide in TR-FRET assay buffer. Displacement of the peptide is measured by the decrease in FRET signal. Kd is derived from saturation binding experiments; IC50 is derived from competitive binding dose-response curves. Binding to other bromodomains (BD5, SMARCA2B, SMARCA4) is determined similarly.
|
| Cell Assay |
Cell Viability Assay[1]
Cell Types: Human prostate cell lines LNCaP, PC3, and RWPE -1 Tested Concentrations: 0, 0.1, 1, and 10 μM Incubation Duration: 5 days Experimental Results: Inhibited LNCaP growth at higher concentrations. Cells: A PBRM1-dependent prostate cancer cell line (e.g., LNCaP). Protocol: Cells are treated with PBRM1-BD2-IN-2 at concentrations of 0, 0.1, 1, and 10 uM for 5 days. Cell viability is measured by CellTiter-Glo or MTT assays. Selectivity for PBRM1-dependent cells is shown by comparing to a control cell line that does not express PBRM1. To confirm target engagement, a cellular thermal shift assay (CETSA) or an acetylated histone peptide pull-down from treated cell lysates can be used. |
| Animal Protocol |
No specific in vivo protocol found; please refer to general bromodomain inhibitor protocols. For potential in vivo studies, PBRM1-BD2-IN-2 would likely be formulated in 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline and administered intraperitoneally (IP) at doses of 10-50 mg/kg. Tumor-bearing mice would be treated daily for 2-3 weeks, and tumor volume would be measured. Tumors would be collected for Western blot analysis of target engagement.
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| ADME/Pharmacokinetics |
No specific PK data found; as a small-molecule bromodomain inhibitor (molecular weight ~559 g/mol), PBRM1-BD2-IN-2 likely has moderate oral bioavailability. The compound is cell-active, indicating it can cross cellular membranes. In DMSO, it is soluble. In vivo studies would typically use formulations containing 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline. Detailed PK parameters are not provided.
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| Toxicity/Toxicokinetics |
No specific toxicity data found; please refer to general bromodomain inhibitor properties. At therapeutic doses, bromodomain inhibitors are generally well-tolerated in animal models. However, PBRM1 is a tumor suppressor in some contexts (e.g., ccRCC), so its inhibition could theoretically have differential effects depending on the mutation status. Toxicity studies in normal tissues have not been reported. Use of this compound is restricted to research applications.
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| References | |
| Additional Infomation |
PBRM1-BD2-IN-2 is a selective and cell-active inhibitor of the PBRM1 bromodomain. PBRM1 is a component of the PBAF complex, which is essential for chromatin remodeling and gene expression. Mutations in PBRM1 are common in clear cell renal cell carcinoma (ccRCC), making it a potential therapeutic target. This compound is a chemical tool for validating PBRM1-dependent mechanisms in cancer cells. It is not FDA-approved.
|
| Exact Mass |
310.008
|
|---|---|
| CAS # |
2819989-57-4
|
| PubChem CID |
164880750
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
20
|
| Complexity |
384
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=CC2=C(C(=C1)Cl)C(=O)NC(N2)C3=C(C=CC=C3Cl)F
|
| InChi Key |
LRNRPLFSBRYMGJ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C14H9Cl2FN2O/c15-7-3-1-5-9(17)11(7)13-18-10-6-2-4-8(16)12(10)14(20)19-13/h1-6,13,18H,(H,19,20)
|
| Chemical Name |
5-chloro-2-(2-chloro-6-fluorophenyl)-2,3-dihydro-1H-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
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|---|---|
| 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.) |
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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