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| Targets |
The primary target of BCL6-IN-8c is the B-cell lymphoma 6 (BCL6) protein, a transcriptional repressor that is frequently dysregulated in diffuse large B-cell lymphoma (DLBCL) and other B-cell malignancies. The compound inhibits the interaction between BCL6 and its corepressors, which is essential for BCL6-mediated transcriptional repression. By disrupting this protein-protein interaction, BCL6-IN-8c reactivates BCL6 target genes, including those involved in cell cycle control and apoptosis, leading to the inhibition of BCL6-driven tumor cell growth.
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| ln Vitro |
Additionally, TP-021 (BCL6-IN-8c, compound 8c) shows good submicromolar (M2H IC50 = 0.72 µM) cellular PPI inhibitory activity. Even at 30 µM, TP-021 (BCL6-IN-8c) does not show any appreciable cytotoxicity [1].
BCL6-IN-8c exhibits good cellular protein-protein interaction (PPI) inhibitory activity in the submicromolar range, with a mammalian two-hybrid (M2H) IC50 of 0.72 μM. In cell-free ELISA assays, it demonstrates an IC50 of 0.10 μM for inhibiting the BCL6-corepressor interaction. Importantly, BCL6-IN-8c does not exhibit significant cytotoxicity even at concentrations up to 30 μM, indicating a favorable selectivity profile for the BCL6 target. These in vitro data confirm the compound's potency and specificity as a BCL6 inhibitor. |
| ln Vivo |
TP-021 (BCL6-IN-8c, compound 8c) was studied at doses of 0.1 mg/kg iv and 1 mg/kg po using mouse box dosing procedures to determine its pharmacokinetic properties. With Cmax = 233 ng/mL, Tmax = 2 hours, MRT = 3.3 h, AUC = 1.27 mg·h/mL, and F (oral bio Utilization) = 79.9%, TP-021 (BCL6-IN-8c) demonstrated favorable pharmacokinetic characteristics[1].
BCL6-IN-8c exhibits a good pharmacokinetic profile in mouse cassette-dosing studies, with an oral bioavailability (F) of 79.9%. Key pharmacokinetic parameters include a Cmax of 233 ng/mL, a Tmax of 2 hours, and a mean residence time (MRT) of 3.3 hours. These properties, combined with its oral activity, make BCL6-IN-8c a suitable tool compound for in vivo efficacy studies in mouse models of BCL6-driven lymphomas. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for BCL6-IN-8c typically involve measuring its ability to disrupt the BCL6-corepressor interaction in a cell-free system. The assay uses an enzyme-linked immunosorbent assay (ELISA) format where BCL6 protein is immobilized, and a labeled corepressor peptide is added in the presence of varying concentrations of the compound. The inhibition of corepressor binding is measured, and the IC50 is calculated, with BCL6-IN-8c showing an IC50 of 0.10 μM.
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| Cell Assay |
Cellular assays for BCL6-IN-8c are performed in BCL6-dependent lymphoma cell lines to assess its effects on BCL6 target gene reactivation and cell proliferation. Cells are treated with varying concentrations of the compound, and the expression of BCL6 target genes is measured by quantitative PCR. The compound's effects on cell viability and proliferation are assessed using cell viability assays. The mammalian two-hybrid (M2H) assay is used to measure cellular PPI inhibitory activity, with BCL6-IN-8c showing an IC50 of 0.72 μM.
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| Animal Protocol |
In vivo animal studies with BCL6-IN-8c are typically performed in mouse xenograft models of B-cell lymphoma. Immunodeficient mice are implanted with BCL6-dependent human lymphoma cells, and after tumor establishment, BCL6-IN-8c is administered orally at specified doses. Tumor growth is monitored over time, and at the end of the study, tumors are excised and analyzed for BCL6 target gene expression and apoptosis markers. However, specific efficacy data from these models are not detailed in the available literature.
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| ADME/Pharmacokinetics |
BCL6-IN-8c has a molecular weight of 417.84 and a molecular formula of C20H20ClN3O5. It is soluble in DMSO and is stable when stored as a powder at -20°C for up to 3 years or in solution at -80°C for up to 1 year. The compound exhibits good oral bioavailability (79.9%) in mice, with a Cmax of 233 ng/mL and a Tmax of 2 hours. Detailed pharmacokinetic parameters such as half-life and clearance are not extensively reported.
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| Toxicity/Toxicokinetics |
BCL6-IN-8c does not exhibit significant cytotoxicity even at concentrations up to 30 μM, indicating a favorable safety profile in vitro. However, comprehensive toxicology data for this compound are not extensively reported. As a research-grade compound, it is not intended for human consumption. The compound's selectivity for the BCL6-corepressor interaction suggests a low risk of off-target toxicity, but specific toxicological data are not available in the literature.
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| References | |
| Additional Infomation |
BCL6-IN-8c is a research-grade compound not approved for clinical use. Its primary application is as a pharmacological tool for studying the role of BCL6 in B-cell malignancies. The compound is used to investigate the mechanisms of BCL6-mediated transcriptional repression and to validate BCL6 as a therapeutic target for the treatment of diffuse large B-cell lymphoma and other B-cell cancers. Its oral activity and favorable pharmacokinetic profile make it a valuable tool for preclinical studies.
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| Molecular Formula |
C20H20CLN3O5
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| Molecular Weight |
417.842904090881
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| Exact Mass |
417.109
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| CAS # |
2130878-25-8
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| PubChem CID |
131801156
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
3.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
29
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| Complexity |
597
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=C(C(=CC=1NC1C=CC2=C(C=1)CCC(N2)=O)OC1CCOCC1)[N+](=O)[O-]
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| InChi Key |
RRELDGDKULRRDM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H20ClN3O5/c21-15-10-18(24(26)27)19(29-14-5-7-28-8-6-14)11-17(15)22-13-2-3-16-12(9-13)1-4-20(25)23-16/h2-3,9-11,14,22H,1,4-8H2,(H,23,25)
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| Chemical Name |
6-[2-chloro-4-nitro-5-(oxan-4-yloxy)anilino]-3,4-dihydro-1H-quinolin-2-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 : ≥ 50 mg/mL (~119.66 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.71 mg/mL (1.70 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 7.1 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3933 mL | 11.9663 mL | 23.9326 mL | |
| 5 mM | 0.4787 mL | 2.3933 mL | 4.7865 mL | |
| 10 mM | 0.2393 mL | 1.1966 mL | 2.3933 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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