GSK1070916 (also known as NMI-900 or GSK-1070916A) is a novel, potent, reversible and ATP-competitive inhibitor of Aurora B/C with potential antitumor activity. It inhibits Aurora B/C with IC50 of 3.5 nM/6.5 nM and displays >100-fold selectivity for Aurora B/C over the closely related Aurora A-TPX2 complex. It shows potent in vitro antiproliferative activity and high in vivo antitumor efficacy. GSK1070916 A binds to and inhibits the activity of Aurora kinases B and C, which may result in inhibition of cellular division and a decrease in the proliferation of tumor cells that overexpress the Aurora kinases B and C. Aurora kinases play essential roles in mitotic checkpoint control during mitosis, and are overexpressed by a wide variety of cancer cell types.

Physicochemical Properties

Molecular Formula	C30H33N7O
Molecular Weight	507.63
Exact Mass	507.274
CAS #	942918-07-2
Related CAS #	942918-07-2
PubChem CID	46885626
Appearance	Off-white to light yellow solid powder
Density	1.2±0.1 g/cm3
Index of Refraction	1.651
LogP	5.19
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	7
Heavy Atom Count	38
Complexity	770
Defined Atom Stereocenter Count	0
InChi Key	QTBWCSQGBMPECM-UHFFFAOYSA-N
InChi Code	InChI=1S/C30H33N7O/c1-6-37-19-26(28(34-37)21-10-12-23(13-11-21)32-30(38)36(4)5)24-14-15-31-29-25(24)17-27(33-29)22-9-7-8-20(16-22)18-35(2)3/h7-17,19H,6,18H2,1-5H3,(H,31,33)(H,32,38)
Chemical Name	3-[4-[4-[2-[3-[(dimethylamino)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl]-1-ethylpyrazol-3-yl]phenyl]-1,1-dimethylurea
Synonyms	GSK-1070916A; GSK 1070916A; GSK1070916A;GSK-1070916; GSK 1070916; GSK1070916; NMI 900; NMI900; NMI-900.
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	GSK-1070916 has a modest inhibitory impact on Aurora A/TPX2, with a Ki of 492±61 nM, while it significantly inhibits the kinases of Aurora B/INCENP and Aurora C/INCENP, with Ki of 0.38±0.29 and 1.45±0.35 nM, respectively. Additionally, FLT1, TIE2, SIK, FLT4, and FGFR1 are inhibited by GSK-1070916, with IC50 values of 42, 59, 70, 74, and 78 nM, respectively. GSK-1070916 treatment of human lung cancer A549 cells can result in a strong anti-proliferative impact (EC50=7 nM) [1]. GSK-1070916 has been demonstrated to suppress HH3-S10 phosphorylation in all tumor cell lines, with average EC50 values ranging from 8 to 118 nM [2]. The compound also inhibits a panel of tumor cell lines.
ln Vivo	GSK-1070916 injected intraperitoneally (i.p.) suppresses HH3-S10 phosphorylation in a dose-dependent manner in nude mice implanted with human colon tumor (HCT116) xenografts. Upon repeated intraperitoneal (i.p.) administration of GSK-1070916, four out of eight tumor types (lung, A549; colon, HCT116; acute myelogenous leukemia (AML), HL60; and chronic myelogenous leukemia, K562) exhibit complete or partial antitumor activity; three of the eight exhibit stable disease (colon, Colo205; lung, H460; and breast, MCF-7); and one of the eight tumor types (colon, SW620) exhibits tumor growth delay. In general, GSK-1070916 is well tolerated when taken daily[2].
Animal Protocol	Formulated in 2% Cremophor EL, 2% N,N-dimethylacetamide, and 96% acidified water (pH 5.0); 25, 50, or 100 mg/kg; i.p. injection. Mice tumor xenograft models (A549, SW620, HCT116, H460, MCF-7, HL60, K562, Colo205)
References	[1]. Discovery of GSK-1070916, a potent and selective inhibitor of Aurora B/C kinase. J Med Chem. 2010 May 27;53(10):3973-4001. [2]. GSK-1070916, a potent Aurora B/C kinase inhibitor with broad antitumor activity in tissue culture cells and human tumor xenograft models. Mol Cancer Ther. 2009 Jul;8(7):1808-17.
Additional Infomation	3-[4-[4-[2-[3-[(dimethylamino)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl]-1-ethyl-3-pyrazolyl]phenyl]-1,1-dimethylurea is a member of pyrazoles and a ring assembly.

Solubility Data

Solubility (In Vitro)

DMSO: 102 mg/mL (200.9 mM) Water:<1 mg/mL Ethanol: N/a

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.67 mg/mL (3.29 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 16.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.67 mg/mL (3.29 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 16.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 1 mg/mL (1.97 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 10.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 2% Cremophor EL, 2% N,N-dimethylacetamide, pH 5.0:~30mg/mL  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.9699 mL	9.8497 mL	19.6994 mL
	5 mM	0.3940 mL	1.9699 mL	3.9399 mL
	10 mM	0.1970 mL	0.9850 mL	1.9699 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.