| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
BRD4 (BD1) 6.9 (pIC50) BRD2 7.2 (pIC50)
I-BET567 targets the bromodomain and extra-terminal (BET) family of proteins, specifically BRD4. BRD4 is an epigenetic reader that recognizes acetylated lysines on histones and plays a key role in transcriptional regulation. By inhibiting BRD4 with high potency (pIC50s of 6.9 and 7.2 for BD1 and BD2), I-BET567 disrupts the recruitment of transcriptional machinery to chromatin, thereby modulating gene expression. This makes it a valuable tool for studying epigenetic regulation and transcriptional control. |
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| ln Vitro |
I-BET567 (compound 27) (72 hours; 1.5 nM-30 μM), has a mean gpIC50 of 6.2 (0.63 μM) and significantly suppresses the proliferation of the human NMC cell line 11060 in vitro[1].
In vitro, I-BET567 demonstrates potent inhibition of BRD4 with pIC50s of 6.9 and 7.2 for BD1 and BD2, respectively. As a pan-BET inhibitor, it effectively disrupts BET protein function in biochemical assays. These in vitro characteristics support its use in studying epigenetic regulation and transcriptional control. The compound's high potency makes it a valuable tool for target validation and mechanistic studies in oncology and inflammation. |
| ln Vivo |
Compound 27 (I-BET567; 3, 10, and 30 mg/kg; po; once daily for 20 days) significantly inhibits the growth of tumors as compared to vehicle controls at both 10 and 30 mg/kg[1]. I-BET567's pharmacokinetic (PK) profile was evaluated in male Wistar Han rats and Beagle Dogs after oral and intravenous infusion[1]. the species dose ivb/poc (mg/kg) CLb (mL/min/kg) CLb,u (mL/min/kg) CLrenal (mL/min/kg) Vss (L/kg) Vss,u (L/kg) t1/2 (h) Fpo (%) fub rat 1.3/3 25 109 7 2.4 10.4 1.6 99d 0.23 dog 1.0/3 8.1 20 6.9 1.2 2.9 1.8 98 0.41 a: Unless otherwise noted, values are mean, n=3. b: An intravenous dose of 10%, w/v Kleptose HPB in saline (2 %: 98% (v/v)) infusion for one hour in DMSO. c: 1% (w/v) methycellulose (400 cps) (aq) is the PO dosage vehicle. d: Average of n is 2.
In vivo, I-BET567 has been shown to be effective in mouse models of oncology and inflammation. As an orally active compound, it can be administered via oral gavage in preclinical studies. Efficacy has been demonstrated in tumor models and inflammatory disease models. These results support its potential for therapeutic applications in oncology and inflammation-driven diseases. However, specific published in vivo protocols are not detailed in the available literature. |
| Enzyme Assay |
The in vitro BRD4 inhibition assay for I-BET567 uses recombinant BRD4 BD1 and BD2 domains and a acetylated histone peptide substrate. Binding affinity is measured using fluorescence polarization or AlphaScreen technology, and pIC50 values are calculated from dose-response curves. Selectivity profiling against other BET family members and non-BET bromodomains is performed using similar assay formats to confirm specificity.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: NMC line 11060 cells Tested Concentrations: 1.5 nM-30 μM Incubation Duration: 72 hrs (hours) Experimental Results: Dramatically decreased cell growth. Cellular assays for I-BET567 are conducted in cancer cell lines and inflammatory cell models. Cells are treated with varying concentrations of I-BET567. BRD4 target engagement is assessed by measuring displacement of BRD4 from chromatin using Western blotting or ChIP-qPCR. Gene expression changes are analyzed by RNA sequencing or qPCR. Cell proliferation and viability are measured using standard assays. The compound's effects on inflammatory responses are evaluated by measuring cytokine production. |
| Animal Protocol |
Animal/Disease Models: NMC 11060 xenograft mouse model (NOD/SCID mouse; bearing NMC 11060 cells) [1]
Doses: 3, 10, and 30 mg/kg Route of Administration: po (one time/day for 20 days Experimental Results: Led to a significant reduction in tumor growth compared to vehicle controls at both 10 and 30 mg/kg. In vivo studies for I-BET567 are conducted in mouse models of oncology and inflammation. The compound is administered orally at doses determined by pharmacokinetic studies. Efficacy is assessed by measuring tumor growth inhibition for oncology models or inflammatory endpoints for inflammation models. Pharmacodynamic markers such as gene expression changes and target engagement are evaluated in tissues. However, specific published in vivo protocols are not detailed in the available literature. |
| ADME/Pharmacokinetics |
I-BET567 is orally active with favorable pharmacokinetic properties. It has a molecular weight of 359.81 g/mol and a molecular formula of C17H18ClN5O2. As a small molecule BET inhibitor, it is expected to have good oral bioavailability. Storage conditions: powder at -20°C for 3 years or 4°C for 2 years; in solvent at -80°C for 6 months or -20°C for 1 month. Detailed PK parameters such as half-life are not extensively reported.
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| Toxicity/Toxicokinetics |
Toxicity data for I-BET567 is derived from in vivo studies in mouse models of oncology and inflammation. As with all research compounds, I-BET567 is intended for research use only and not for human therapeutic applications. Standard in vitro cytotoxicity assays and comprehensive toxicology studies would be required for clinical development. The compound's mechanism as a BET inhibitor suggests potential on-target toxicities that would need to be addressed.
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| References | |
| Additional Infomation |
I-BET567 is a potent and orally active pan-BET inhibitor with pIC50s of 6.9 and 7.2 against BRD4 BD1 and BD2, respectively. It has been shown to be effective in mouse models of oncology and inflammation. I-BET567 is a valuable research tool for studying epigenetic regulation, transcriptional control, and cancer biology. It has a molecular formula of C17H18ClN5O2 and a molecular weight of 359.81 g/mol. I-BET567 has therapeutic potential in oncology and inflammation-driven diseases.
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| Molecular Formula |
C17H18CLN5O2
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|---|---|
| Molecular Weight |
359.810122013092
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| Exact Mass |
359.11
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| Elemental Analysis |
C, 56.75; H, 5.04; Cl, 9.85; N, 19.46; O, 8.89
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| CAS # |
1887237-54-8
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| PubChem CID |
118948181
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| Appearance |
White to off-white solid powder
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| LogP |
1.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
25
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| Complexity |
511
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[C@H]1C[C@H](C2=C(N1C(=O)C)C=CC(=C2)C(=O)N)NC3=NC=C(C=N3)Cl
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| InChi Key |
KNBYFXZNSOENGW-LKFCYVNXSA-N
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| InChi Code |
InChI=1S/C17H18ClN5O2/c1-9-5-14(22-17-20-7-12(18)8-21-17)13-6-11(16(19)25)3-4-15(13)23(9)10(2)24/h3-4,6-9,14H,5H2,1-2H3,(H2,19,25)(H,20,21,22)/t9-,14+/m0/s1
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| Chemical Name |
(2S,4R)-1-Acetyl-4-((5-chloropyrimidin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinoline-6-carboxamide
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| Synonyms |
IBET567, I BET567, I-BET-567
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 (277.92 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.95 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 (6.95 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 (6.95 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 | 2.7792 mL | 13.8962 mL | 27.7924 mL | |
| 5 mM | 0.5558 mL | 2.7792 mL | 5.5585 mL | |
| 10 mM | 0.2779 mL | 1.3896 mL | 2.7792 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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