GDP366 is a novel, potent, selective small molecule and dual inhibitor of survivin and Op18, it induces cell growth inhibition, cellular senescence and mitotic catastrophe in human cancer cells. Survivin appears to be essential for cell cycle progression as well as cell survival, according to mounting evidence. Op18/stathmin is an oncoprotein that controls the stabilization of microtubules. Op18 and survivin have both been suggested as potential therapeutic targets for cancer. However, only a small number of small molecule survivin and Op18 inhibitors have been reported. GDP366 potently and selectively inhibited the expression of both survivin and Op18. Survivin and Op18 saw a decline in their protein and mRNA levels. Although the levels of p53 and p21 were potently raised by GDP366, this inhibitory effect was not reliant on their health. In vivo (nude mouse model) and in vitro (GDP366), tumor cell growth was markedly inhibited by GDP366 without apoptosis being induced quickly. In several different cancer cell lines, GDP366 induced polyploidy. By decreasing the activity of the telomerase enzyme, GDP366 accelerated chromosomal instability and triggered cellular senescence. According to our findings, GDP366 is a brand-new dual inhibitor of Op18 and Survivin. Additional translational testing of this compound is warranted in light of our findings.

Physicochemical Properties

Molecular Formula	C20H17N5OS
Molecular Weight	375.44688
Exact Mass	375.115
Elemental Analysis	C, 63.98; H, 4.56; N, 18.65; O, 4.26; S, 8.54
CAS #	501698-03-9
Related CAS #	501698-03-9
PubChem CID	6539985
Appearance	Light yellow to yellow solid powder
LogP	3.8
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	3
Heavy Atom Count	27
Complexity	513
Defined Atom Stereocenter Count	0
InChi Key	DZSUJUOJJJCWGG-UHFFFAOYSA-N
InChi Code	InChI=1S/C20H17N5OS/c1-12-3-2-4-15(9-12)25-20(26)24-14-7-5-13(6-8-14)16-10-27-19-17(16)18(21)22-11-23-19/h2-11H,1H3,(H2,21,22,23)(H2,24,25,26)
Chemical Name	1-[4-(4-aminothieno[2,3-d]pyrimidin-5-yl)phenyl]-3-(3-methylphenyl)urea
Synonyms	GDP 366; GDP366; GDP-366
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

Targets	Survivin; Op18
ln Vitro	Survivin and Op18 expression are both potently and specifically inhibited by GDP366. Survivin and Op18 have lower mRNA and protein levels as a result of GDP366. Despite the fact that GDP366 significantly raises the levels of p53 and p21, this inhibitory effect is not reliant on their health. In vitro and in vivo (using a nude mouse model), GDP366 significantly slows the growth of tumor cells without quickly inducing apoptosis. Multiple kinds of cancer cell lines are induced to become polyploid by GDP366. By decreasing telomerase activity, GDP366 causes chromosomal instability to increase and accelerates cellular senescence[1].
References	[1]. GDP366, a novel small molecule dual inhibitor of survivin and Op18, induces cell growth inhibition, cellular senescence and mitotic catastrophe in human cancer cells. Cancer Biol Ther. 2010 Apr 15;9(8):640-50.

Solubility Data

Solubility (In Vitro)

DMSO: ~62.5 mg/mL (~166.5 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.54 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 20.8 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	2.6635 mL	13.3174 mL	26.6347 mL
	5 mM	0.5327 mL	2.6635 mL	5.3269 mL
	10 mM	0.2663 mL	1.3317 mL	2.6635 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.