hSMG-1 inhibitor 11j, a pyrimidine analogue, is a potent and specific hSMG-1 inhibitor (antagonist) with IC50 of 0.11 nM. hSMG-1 inhibitor 11j is more than 455 times more selective for hSMG-1 than mTOR (IC50=50 nM), PI3Kα/γ (IC50=92/60 nM) and CDK1/CDK2 (IC50=32/7.1 μM). hSMG-1 inhibitor 11j may be utilized in cancer research.

Physicochemical Properties

Molecular Formula	C27H28CLN7O3S
Molecular Weight	566.07
Exact Mass	565.166
CAS #	1402452-15-6
PubChem CID	71458575
Appearance	White to yellow solid powder
Density	1.4±0.1 g/cm3
Index of Refraction	1.640
LogP	4.38
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	9
Heavy Atom Count	39
Complexity	879
Defined Atom Stereocenter Count	0
InChi Key	RZFJBSIAXYEPBX-UHFFFAOYSA-N
InChi Code	InChI=1S/C27H28ClN7O3S/c1-4-35(5-2)39(37,38)25-17-21(10-11-22(25)28)32-26-31-15-13-23(34-26)19-12-14-30-24(16-19)18-6-8-20(9-7-18)33-27(36)29-3/h6-17H,4-5H2,1-3H3,(H2,29,33,36)(H,31,32,34)
Chemical Name	1-[4-[4-[2-[4-chloro-3-(diethylsulfamoyl)anilino]pyrimidin-4-yl]pyridin-2-yl]phenyl]-3-methylurea
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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.
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

Targets	hSMG-1 0.11 nM (IC50) mTOR 50 nM (IC50) PI3Kγ 60 nM (IC50) PI3Kα 92 nM (IC50) GSKα 260 (IC50) GSKβ 330 (IC50) CDK2 7.1 μM (IC50) CDK1 32 μM (IC50)
ln Vitro	In MDA 361 cells, hSMG-1 inhibitor 11j (0.3-3 μM; 6 h) dramatically lowers UPF1 phosphorylation at 0.3 μM and completely removes it at 1 μM[1]. With an IC50 of 75 nM, hSMG-1 inhibitor 11j suppresses MDA468 cell proliferation[1].
References	[1]. Identification of pyrimidine derivatives as hSMG-1 inhibitors. Bioorg Med Chem Lett. 2012 Nov 1;22(21):6636-41.

Solubility Data

Solubility (In Vitro)

DMSO : 80 mg/mL (141.33 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 6 mg/mL (10.60 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 60.0 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.7666 mL	8.8328 mL	17.6657 mL
	5 mM	0.3533 mL	1.7666 mL	3.5331 mL
	10 mM	0.1767 mL	0.8833 mL	1.7666 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.