6-tert-Butyl-2,3-naphthalenedicarbonitrile

Names

[ Name ]:
6-tert-Butyl-2,3-naphthalenedicarbonitrile

[Synonym ]:
6-tert-butylnaphthalene-2,3-dicarbonitrile
MFCD00209558

Biological Activity

[Description]:

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[1][2][3][4].

[Related Catalog]:

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> Microtubule/Tubulin

Signaling Pathways >> Cell Cycle/DNA Damage >> Kinesin

Signaling Pathways >> Cytoskeleton >> Microtubule/Tubulin

Signaling Pathways >> Cytoskeleton >> Kinesin

[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[1]. BRD9876 exhibits approximately 3-fold selectivity for MM1S myeloma cells (IC50=3.1 μM) over CD34+ derived hematopoietic cells (IC50=9.1 μM)[1]. 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[1]. 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[1]. Cell Cycle Analysis[1] Cell Line: MM1S cells and CD34 hematopoietic cells Concentration: 10 μM Incubation Time: 24 hours Result: Revealed rapid arrest of cells at the G2/M phase starting as early as 2h of treatment in MM1S cells. Showed markedly less G2/M arrest in CD34 hematopoietic cells.

[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.

[4]. Geng-Yuan Chen, et al. Eg5 Inhibitors Have Contrasting Effects on Microtubule Stability and Metaphase Spindle Integrity. ACS Chem Biol. 2017 Apr 21;12(4):1038-1046.

Chemical & Physical Properties

[ Density]:
1.11g/cm3

[ Boiling Point ]:
429.7ºC at 760 mmHg

[ Melting Point ]:
185-189ºC(lit.)

[ Molecular Formula ]:
C₁₆H₁₄N₂

[ Molecular Weight ]:
234.29600

[ Flash Point ]:
206.6ºC

[ Exact Mass ]:
234.11600

[ PSA ]:
47.58000

[ LogP ]:
3.88066

[ Index of Refraction ]:
1.603

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302-H312-H332

[ Precautionary Statements ]:
P280

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xn: Harmful;

[ Risk Phrases ]:
20/21/22

[ Safety Phrases ]:
36

[ RIDADR ]:
NONH for all modes of transport

[ HS Code ]:
2926909090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2926909090

[ Summary ]:
HS:2926909090 other nitrile-function compounds VAT:17.0% Tax rebate rate:9.0% Supervision conditions:none MFN tariff:6.5% General tariff:30.0%