BRD9876

BRD9876 is the “rigor” inhibitor that locks kinesin-5 (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. BRD9876 specifically targets microtubule-bound Eg5 and selectively inhibits myeloma over CD34 cells. BRD9876 has the potential for multiple myeloma (MM) research.

Product information

CAS Number: 32703-82-5

Molecular Weight: 234.30

Formula: C16H14N2

Chemical Name: 6-tert-butylnaphthalene-2,3-dicarbonitrile

Smiles: CC(C)(C)C1=CC2=CC(C#N)=C(C=C2C=C1)C#N

InChiKey: MKILROQBJOOZKC-UHFFFAOYSA-N

InChi: 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

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 50 mg/mL (213.40 mM; Need ultrasonic).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

BRD9876 (10 μM; 24 hours) reveales rapid arrest of cells at the G2/M phase starting as early as 2h of treatment in MM1S cells. BRD9876 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 uM) 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 with BRD9876 against primary MM cells. BRD9876 is completely ineffective at inhibiting the basal ATPase activity of Eg5, in contrast to loop L5-binding monastrol or α4/α6-binding BI8 which shows greater activity against basal Eg5 ATPase activity.

References:

1. Shrikanta Chattopadhyay, et al. Niche-Based Screening in Multiple Myeloma Identifies a Kinesin-5 Inhibitor with Improved Selectivity over Hematopoietic Progenitors. Cell Rep. 2015 Feb 10;10(5):755-770.
2. Chieh-Ting Fang, et al. HSP70 regulates Eg5 distribution within the mitotic spindle and modulates the cytotoxicity of Eg5 inhibitors. Cell Death Dis. 2020 Sep 1;11(8):715.
3. Anke Maes, et al. The therapeutic potential of cell cycle targeting in multiple myeloma. Oncotarget. 2017 Jun 28;8(52):90501-90520.

Products are for research use only. Not for human use.