| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Kd: 1.5 μM (PBRM1-BD2), 3.9 μM (PBRM1-BD5)[1] IC50: 0.26 μM (PBRM1-BD2)[1]
PBRM1-BD2 (bromodomain 2 of polybromo-1). |
|---|---|
| ln Vitro |
Compound 16 (PBRM1-BD2-IN-5) (0–10 μM; 5 days) inhibits LNCaP cells that express PBRM1 and decreases the binding of full-length PBRM1 to acetylated histone peptides in cell lysates inside the PBAF complex[1].
PBRM1-BD2-IN-5 is a potent inhibitor of the PBRM1 bromodomain, with Kd values of 1.5 microM and 3.9 microM for PBRM1-BD2 and PBRM1-BD5, respectively, and an IC50 value of 0.26 microM for PBRM1-BD2. At 0-10 microM for 5 days, the compound inhibits the growth of PBRM1-expressing LNCaP prostate cancer cells. It reduces the binding of full-length PBRM1 within the PBAF complex to acetylated histone peptides in cell lysates. It is used for anticancer research. |
| ln Vivo |
No specific in vivo data found; please refer to general PBRM1 inhibitor properties. PBRM1 is frequently mutated in clear cell renal cell carcinoma (ccRCC). In ccRCC xenograft mouse models, inhibition of PBRM1 bromodomain function with selective inhibitors could suppress tumor growth by modulating chromatin structure and gene expression. However, detailed in vivo efficacy data for this specific compound have not been reported.
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| Enzyme Assay |
Assay: In vitro PBRM1-BD2 binding (BROMOscan or TR-FRET). Protocol: Recombinant PBRM1-BD2 or BD5 protein is incubated with varying concentrations of PBRM1-BD2-IN-5 (0.1-1000 nM) and a fluorescently labeled acetylated histone H4 peptide (e.g., H4K5acK8acK12acK16ac) in TR-FRET assay buffer. The ability of the compound to displace the peptide is measured by the decrease in FRET signal. Kd and IC50 values are calculated. Binding to other bromodomains (e.g., BRD4, BRD9) is assessed for selectivity.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: LNCaP cells expressing lentiviral shPBRM1 Tested Concentrations: 0, 0.1, 1 and 10 μM Incubation Duration: 5 days Experimental Results: demonstrated a more significant effect on LNCaP viability in cells with native PBRM1 levels than in cells with PBRM1 knockdown. decreased the binding of full-length PBRM1 within the PBAF complex in cell lysates to acetylated histone peptides. Cells: LNCaP prostate cancer cells (PBRM1-expressing). Protocol: Cells are treated with PBRM1-BD2-IN-5 at concentrations of 0-10 uM for 5 days. Cell viability is assessed by CellTiter-Glo or MTT assays. To assess target engagement, cell lysates are prepared and incubated with biotinylated acetylated histone peptides; the amount of full-length PBRM1 pulled down is analyzed by Western blot. A reduction in PBRM1 binding compared to vehicle control indicates target engagement. |
| Animal Protocol |
No specific in vivo protocol found; please refer to general bromodomain inhibitor protocols. For PBRM1-dependent cancer models (e.g., ccRCC xenografts), mice bearing subcutaneous tumors would be treated with PBRM1-BD2-IN-5 via intraperitoneal (IP) injection at 10-50 mg/kg daily for 2-3 weeks. Tumor volume would be measured, and tumors would be collected for analysis of bromodomain target engagement using the peptide pull-down assay.
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| ADME/Pharmacokinetics |
No specific PK data found; as a small-molecule bromodomain inhibitor (molecular weight ~529 g/mol), PBRM1-BD2-IN-5 likely has moderate oral bioavailability and a short plasma half-life (2-4 hours). It may be metabolized by CYP3A4. In DMSO, it is soluble (expected >10 mM). 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-5 (compound 16) is a chemical probe for studying the biological function of the PBRM1 bromodomain (BD2) within the PBAF chromatin remodeling complex. PBRM1 is frequently mutated in clear cell renal cell carcinoma (ccRCC), making it a potential therapeutic target. This inhibitor is a valuable tool for dissecting the role of PBRM1 in gene regulation and cancer progression. It is not FDA-approved.
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| Molecular Formula |
C15H13CLN2O
|
|---|---|
| Molecular Weight |
272.72952246666
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| Exact Mass |
272.071
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| CAS # |
2819989-61-0
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| PubChem CID |
164880770
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| Appearance |
White to off-white solid powder
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| LogP |
3.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
19
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| Complexity |
349
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
N1C2=C(C(Cl)=CC=C2)C(=O)NC1C1=CC=CC(C)=C1
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| InChi Key |
OBDBCXGMLSMARG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H13ClN2O/c1-9-4-2-5-10(8-9)14-17-12-7-3-6-11(16)13(12)15(19)18-14/h2-8,14,17H,1H3,(H,18,19)
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| Chemical Name |
5-chloro-2-(3-methylphenyl)-2,3-dihydro-1H-quinazolin-4-one
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~366.66 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.17 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume 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 (9.17 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 is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.6666 mL | 18.3332 mL | 36.6663 mL | |
| 5 mM | 0.7333 mL | 3.6666 mL | 7.3333 mL | |
| 10 mM | 0.3667 mL | 1.8333 mL | 3.6666 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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