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Purity: ≥98%
PLX51107 is a novel, potent and selective BET (Bromodomain and Extra-Terminal motif) inhibitor, also called BRD4 (bromodomain and extra terminal domain) inhibitor with Kd values of 1.6, 2.1, 1.7, and 5 nM for BD1 and 5.9, 6.2, 6.1, and 120 nM for BD2 of BRD2, BRD3, BRD4, and BRDT, respectively; BRD4 is overexpressed in CLL and is enriched proximal to genes upregulated or de novo expressed in CLL with known functions in disease pathogenesis and progression. PLX51107 also interacts with the bromodomains of CBP and EP300 with Kd in the 100 nM range. As a structurally distinct BET inhibitor, PLX51107 demonstrated potent in vitro and in vivo pharmacologic properties that emulates or exceeds the efficacy of BCR signaling agents in preclinical models of CLL. PLX51107 binds to the acetylated lysine recognition motifs in the bromodomains of the BRD4 protein, thereby preventing the binding of BRD4 to acetylated lysines on histones, which disrupts chromatin remodeling and gene expression. The discovery of the involvement of BRD4 in the core CLL transcriptional program provides a compelling rationale for clinical investigation of PLX51107 as epigenetic therapy in CLL and application of BRD4 profiling in other cancers.
| ln Vitro |
With Kds of 1.6, 2.1, 1.7, and 5 nM for BD1, 5.9, 6.2, 6.1, and 120 nM for BRD2, BRD3, and BRD4, respectively, and BRDT, PLX51107 is a strong and selective BET inhibitor. Additionally, PLX51107 interacts with EP300's and CBP's bromodomains (Kd, within a 100 nM range). PLX51107 (0.156-10 μM) prevents primary chronic lymphocytic leukemia (CLL) cells from proliferating when exposed to CpG. In addition, PLX51107 lowers c-MYC levels, increases p21 and IκBα accumulation, and modifies pro- and anti-apoptotic proteins. CLL driver genes are specifically regulated by PLX51107 [1].
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| ln Vivo |
In the Ba/F3 (mouse IL3-dependent pre-B cell line) splenomegaly mouse model, PLX51107 (2 mg/kg, orally) reduced splenomegaly by 75%, with results resembling those of 25 mg/kg OTX015. When taken orally once daily, PLX51107 (20 mg/kg, qd, po) shows strong antileukemia effects in models of Richter transformation (RT) and aggressive chronic lymphocytic leukemia (CLL) [1].
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| References |
[1]. Ozer HG, et al. BRD4 Profiling Identifies Critical Chronic Lymphocytic Leukemia Oncogenic Circuits and Reveals Sensitivity to PLX51107, a Novel Structurally Distinct BET Inhibitor. Cancer Discov. 2018 Apr;8(4):458-477
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| Molecular Formula |
C26H22N4O3
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| Molecular Weight |
438.49
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| CAS # |
1627929-55-8
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| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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| SMILES |
O=C(O)C1=CC=C(C2=CN([ C@H](C3=NC=CC=C3)C)C4=CC(C5=C(C)ON=C5C)=CN=C42)C=C1
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| Chemical Name |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.70 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 (5.70 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.70 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2806 mL | 11.4028 mL | 22.8055 mL | |
| 5 mM | 0.4561 mL | 2.2806 mL | 4.5611 mL | |
| 10 mM | 0.2281 mL | 1.1403 mL | 2.2806 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.
Scaffold-based discovery and cellular profile of PLX51107 as a nonbenzodiazepine BET inhibitor targeting the inducible ZA channel.Cancer Discov.2018 Apr;8(4):458-477. |
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Cytotoxic effect of BET inhibition in malignant B-cell lines and CLL patient-derived B cells is independent of survival signals.Cancer Discov.2018 Apr;8(4):458-477. |
Epigenetic characterization of BET inhibition in primary CLL.Cancer Discov.2018 Apr;8(4):458-477. |
Targeting BRD4 with PLX51107 proves potent antileukemic effects in disease models of aggressive CLL and RT.Cancer Discov.2018 Apr;8(4):458-477. |
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PLX51107 demonstratesin vivoantitumor effects in a preclinical model of aggressive leukemia/lymphoma.Cancer Discov.2018 Apr;8(4):458-477. |
BRD4 inhibition modulates key CLL pathways.Cancer Discov.2018 Apr;8(4):458-477. |
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