942918-07-2

Usage

Uses

Used in Pharmaceutical Industry:
GSK1070916 is used as an anticancer agent for its ability to inhibit Aurora B/C kinase, a key enzyme involved in cell division and proliferation. Its broad antitumor activity in tissue culture cells and human tumor xenograft models highlights its potential in treating various types of cancer.
Additionally, the compound may be utilized in the development of targeted drug delivery systems to enhance its therapeutic efficacy and minimize side effects. This could involve encapsulating GSK1070916 within nanoparticles or other carriers to improve its bioavailability and delivery to cancer cells, thereby increasing its effectiveness in cancer treatment.

Biological Activity

gsk1070916 is a potent and selective inhibitor of aurora b/c kinase with ki values of 0.38nm and 1.5nm, respectively [1].gsk1070916 is a reversible atp-competitive inhibitor of aurora b and aurora c with ki values of 0.38nm and 1.5nm, respectively. the spa assay shows gsk1070916 has a good selectivity over aurora a. it inhibits aurora b with ic50 value of 5nm but 1259nm for aurora a. it is also reported that treatment of gsk1070916 suppresses cell proliferation in a549 human lung cancer cells with ec50 value of 7nm. moreover, both in vitro and in vivo assays demonstrate gsk1070916 can inhibit the phosphorylation of histone h3, which is a substrate of aurora b. gsk1070916 can also suppress tumor growth in mice with hl-60 tumor xenografts [1].

references

[1] adams nd, adams jl, burgess jl, chaudhari am, copeland ra, donatelli ca, drewry dh, fisher ke, hamajima t, hardwicke ma, huffman wf, koretke-brown kk, lai zv, mcdonald ob, nakamura h, newlander ka, oleykowski ca, parrish ca, patrick dr, plant r, sarpong ma, sasaki k, schmidt sj, silva dj, sutton d, tang j, thompson cs, tummino pj, wang jc, xiang h, yang j, dhanak d. discovery of gsk1070916, a potent and selective inhibitor of aurora b/c kinase. j med chem. 2010 may 27;53(10):3973-4001.

Upstream product

• 124-40-3 dimethyl amine 
• 942918-99-2 N'-(4-{1-ethyl-4-[2-(3-formylphenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-1H-pyrazol-3-yl}phenyl)-N,N-dimethylurea 
• 942919-53-1 4-[3-(4-aminophenyl)-1-ethyl-1H-pyrazol-4-yl]-2-[3-(dimethylaminomethyl)phenyl]-1H-pyrrolo[2,3-b]pyridine 

Relevant academic research and scientific papers

Discovery of GSK1070916, a potent and selective inhibitor of aurora B/C kinase

The Aurora kinases play critical roles in the regulation of mitosis and are frequently overexpressed or amplified in human tumors. Selective inhibitors may provide a new therapy for the treatment of tumors with Aurora kinase amplification. Herein we describe our lead optimization efforts within a 7-azaindole-based series culminating in the identification of GSK1070916 (17k). Key to the advancement of the series was the introduction of a 2-aryl group containing a basic amine onto the azaindole leading to significantly improved cellular activity. Compound 17k is a potent and selective ATP-competitive inhibitor of Aurora B and C with Ki* values of 0.38 ± 0.29 and 1.5 ± 0.4 nM, respectively, and is >250-fold selective over Aurora A. Biochemical characterization revealed that compound 17k has an extremely slow dissociation half-life from Aurora B (>480 min), distinguishing it from clinical compounds 1 and 2. In vitro treatment of A549 human lung cancer cells with compound 17k results in a potent antiproliferative effect (EC50 = 7 nM). Intraperitoneal administration of 17k in mice bearing human tumor xenografts leads to inhibition of histone H3 phosphorylation at serine 10 in human colon cancer (Colo205) and tumor regression in human leukemia (HL-60). Compound 17k is being progressed to human clinical trials.

AZAINDOLE INHIBITORS OF AURORA KINASES

The present invention relates to a compound represented by Formula (I): and pharmaceutically acceptable salts. Compounds of the present invention inhibit Aurora kinase, making them especially suitable for the treatment of a number of diseases, including s