| Size | Price | Stock | Qty |
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| 100mg |
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| 250mg |
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| 500mg |
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| Other Sizes |
| Targets |
Kinesin-5 (Eg5, KIF11), a mitotic kinesin essential for bipolar spindle formation. BRD9876 is an ATP- and ADP-competitive Eg5 inhibitor with a Ki of 4 nM. It functions as a "rigor" inhibitor that locks Eg5 in a state with enhanced microtubules (MTs) binding, leading to bundling and stabilization of MTs. BRD9876 interacts with the tyrosine 104 residue that is part of the α4-α6 allosteric binding pocket.
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| ln Vitro |
As early as two hours after treating MM1S cells, BRD9876 (10 μM; 24 hours) rapidly arrests cells in the G2/M phase [1]. Compared to CD34+-derived hematopoietic cells (IC50=9.1 μM), BRD9876 is around three times more selective for MM1S myeloma cells (IC50=3.1 μM) [1]. The stromal resistance of bone marrow stromal cells (BMSCs) from MM bone marrow aspirates in MM1S cells can be overcome by BRD9876 (0.1, 1, 10, 100 uM); however, BRD9876 has very little effect on primary MM cells [1]. While cyclic L5 paired with monastrol or α4/α6 combined with BI8 display higher activity on baseline Eg5 ATPase activity, BRD9876 is absolutely ineffective in reducing this activity [1].
BRD9876 (10 µM; 24 hours) rapidly arrests MM1S cells in the G2/M phase, starting as early as 2 hours of treatment. It exhibits approximately 3-fold selectivity for MM1S myeloma cells (IC₅₀ = 3.1 µM) over CD34+ derived hematopoietic cells (IC₅₀ = 9.1 µM). BRD9876 (0.1, 1, 10, 100 µM) is able to overcome, in MM1S cells, stromal resistance of bone marrow stromal cells (BMSCs) from MM bone marrow aspirates, but only minimal effects are observed against primary MM cells. |
| ln Vivo |
BRD9876 is a "rigor" inhibitor that locks kinesin-5 (Eg5) in a state with enhanced microtubules (MTs) binding, leading to bundling and stabilization of MTs. It specifically targets microtubule-bound Eg5 and selectively inhibits myeloma over CD34 cells, showing potential for multiple myeloma (MM) research.
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| Enzyme Assay |
In vitro enzyme assays for BRD9876 involve measuring its inhibition of Eg5 ATPase activity in the presence of microtubules. Recombinant Eg5 motor domain is incubated with microtubules, ATP, and various concentrations of BRD9876. ATPase activity is measured by detecting the release of inorganic phosphate. BRD9876 acts as a competitive inhibitor of ATP and inhibits Eg5-mediated microtubule gliding.
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| Cell Assay |
Cell cycle analysis [1]
Cell Types: MM1S cells and CD34 hematopoietic cells Tested Concentrations: 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: In MM1S cells, cells rapidly arrested in the G2/M phase as early as 2 hrs (hours) after treatment. The G2/M phase arrest of CD34 hematopoietic cells was Dramatically diminished. In vitro cellular assays for BRD9876 involve treating MM1S myeloma cells or CD34+ hematopoietic cells with the compound and measuring cell viability, cell cycle distribution, and proliferation. Cells are treated with various concentrations of BRD9876, and cell viability is assessed using metabolic assays. Cell cycle analysis is performed by flow cytometry to detect G2/M arrest. The compound's selectivity for myeloma cells over normal hematopoietic progenitors is evaluated. |
| Animal Protocol |
In vivo animal studies for BRD9876 are limited as the compound is primarily used as a research tool for in vitro applications. The compound's selectivity for MM1S myeloma cells over CD34+ hematopoietic cells and its ability to overcome stromal resistance suggest potential for multiple myeloma research. Further in vivo studies are needed to fully characterize its efficacy.
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| ADME/Pharmacokinetics |
BRD9876 has a molecular weight of 234.30 and a molecular formula of C₁₆H₁₄N₂. It is a white solid with a relative density of 1.11 g/cm³. The compound is soluble in DMSO (50 mg/mL). For storage, powder should be kept at -20°C for up to 3 years, and in solvent at -80°C for up to 6 months or -20°C for 1 month.
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| Toxicity/Toxicokinetics |
BRD9876 displays selectivity over normal hematopoietic progenitors and is approximately 3-fold more selective for MM1S myeloma cells (IC₅₀ = 3.1 µM) over CD34+ derived hematopoietic cells (IC₅₀ = 9.1 µM). BRD9876 is completely ineffective at overcoming stromal resistance in primary MM cells.
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| References |
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| Additional Infomation |
6-tert-butylnaphthalene-2,3-dionitrile is a member of the naphthalene family.
BRD9876 is a "rigor" inhibitor of kinesin-5 (Eg5) that locks the protein in a conformation with enhanced microtubule binding, promoting microtubule bundling and stabilization. It is an ATP- and ADP-competitive Eg5 inhibitor with a Ki of 4 nM. BRD9876 specifically targets microtubule-bound Eg5 and selectively inhibits myeloma over CD34 cells, showing potential for multiple myeloma (MM) research. |
| Molecular Formula |
C16H14N2
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|---|---|
| Molecular Weight |
234.3
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| Exact Mass |
234.116
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| CAS # |
32703-82-5
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| PubChem CID |
613000
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| Appearance |
White to yellow solid powder
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| Density |
1.11g/cm3
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| Boiling Point |
429.7ºC at 760 mmHg
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| Melting Point |
185-189ºC(lit.)
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| Flash Point |
206.6ºC
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| Index of Refraction |
1.603
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| LogP |
3.88
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
18
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| Complexity |
400
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
MKILROQBJOOZKC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H14N2/c1-16(2,3)15-5-4-11-6-13(9-17)14(10-18)7-12(11)8-15/h4-8H,1-3H3
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| Chemical Name |
6-tert-butylnaphthalene-2,3-dicarbonitrile
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| Synonyms |
BRD 9876; BRD-9876; BRD9876
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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: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 (~213.40 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.67 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 | 4.2680 mL | 21.3402 mL | 42.6803 mL | |
| 5 mM | 0.8536 mL | 4.2680 mL | 8.5361 mL | |
| 10 mM | 0.4268 mL | 2.1340 mL | 4.2680 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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