BI-2536 --- PLK1 and BRD4 Dual Inhibitor

BI-2536 is a potent inhibitor of PLK1 (Polo-like kinase 1, IC50 ~0.83 nM) and BRD4 (IC50 ~37 nM). It also inhibits PLK2 and PLK3 with IC50 of 3.5 nM and 9.0 nM, respectively. BI-2536 treatment ranging from 10 nM to 100 nM leads to the blocking of the recruitment of γ-tubulin and phosphorylation of Apc6 at mitotic centrosomes, inhibition of cohesin release from chromosome arms, induction of monopolar spindles, and other Plk1 dependent processes. BI-2536 inhibits the growth of a panel of 32 human cancer cell lines with EC50 of 2-25 nM. It also displaces BRD4 from chromatin and suppresses c-Myc expression. The combination of inhibitory activities on independent kinase and bromodomain oncogenic pathways exemplifies a new strategy for rational single-agent polypharmacological targeting.

Product information

CAS Number: 755038-02-9

Molecular Weight: 521.65

Formula: C28H39N7O3

Chemical Name: (R)-4-((8-cyclopentyl-7-ethyl-5-methyl-6-oxo-5,6,7,8-tetrahydropteridin-2-yl)amino)-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide

Smiles: CC[C@@H]1C(=O)N(C)C2=CN=C(NC3=CC=C(C=C3OC)C(=O)NC3CCN(C)CC3)N=C2N1C1CCCC1

InChiKey: XQVVPGYIWAGRNI-JOCHJYFZSA-N

InChi: InChI=1S/C28H39N7O3/c1-5-22-27(37)34(3)23-17-29-28(32-25(23)35(22)20-8-6-7-9-20)31-21-11-10-18(16-24(21)38-4)26(36)30-19-12-14-33(2)15-13-19/h10-11,16-17,19-20,22H,5-9,12-15H2,1-4H3,(H,30,36)(H,29,31,32)/t22-/m1/s1

Technical Data

Appearance: Solid Power.

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

Solubility: DMSO up to 40 mM

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:

BI-2536 was used at 0.1-1 µM in vitro.

In Vivo:

BI-2536 was dosed to mice by IV injection at 50 mg/kg once or twice a week in xenograft models. (Formulated in hydrochloric acid (0.1 N), and diluted with 0.9% NaCl)

References:

1. Steegmaier M, et al. BI 2536, a potent and selective inhibitor of polo-like kinase 1, inhibits tumor growth in vivo. (2007) Curr Biol. 17(4):316-22.
2. Nappi TC, et al. Identification of Polo-like kinase 1 as a potential therapeutic target in anaplastic thyroid carcinoma. (2009) Cancer Res. 69(5):1916-23.
3. Ciceri P, et al. Dual kinase-bromodomain inhibitors for rationally designed polypharmacology. (2014) Nat Chem Biol. In press.

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

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