AGN 194310 (VTP-194310) is a high-affinity, potent, and selective pan-antagonist of retinoic acid receptors (RARs) with Kds of 3 nM and 2 nM for RARα, RARβ, and RARγ respectively. ,5 nM.

Physicochemical Properties

Molecular Formula	C28H24O2S
Molecular Weight	424.55
Exact Mass	424.149
CAS #	229961-45-9
PubChem CID	9867046
Appearance	White to off-white solid powder
Density	1.3±0.1 g/cm3
Boiling Point	598.1±50.0 °C at 760 mmHg
Flash Point	315.5±30.1 °C
Vapour Pressure	0.0±1.8 mmHg at 25°C
Index of Refraction	1.683
LogP	9.56
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	5
Heavy Atom Count	31
Complexity	738
Defined Atom Stereocenter Count	0
InChi Key	LHUPKWKWYWOMSK-UHFFFAOYSA-N
InChi Code	InChI=1S/C28H24O2S/c1-4-19-7-12-22(13-8-19)25-18-28(2,3)31-26-16-11-21(17-24(25)26)6-5-20-9-14-23(15-10-20)27(29)30/h7-18H,4H2,1-3H3,(H,29,30)
Chemical Name	4-[2-[4-(4-ethylphenyl)-2,2-dimethylthiochromen-6-yl]ethynyl]benzoic acid
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	In all three cell lines, AGN194310 efficiently prevents colony formation; its IC50 values for LNCaP, PC3, and DU-145 cells are 16 nM, 18 nM, and 34 nM, respectively [2]. colony development is inhibited by AGN 194310 (50 nM, 100 nM; LNCaP, PC-3, and DU-145 cells) at 50 nM (alone) and 100 nM (with TNTPB) concentrations (2). 80% of LNCaP cells undergo apoptosis when exposed to 1 μM of AGN 194310 for 72 hours [2].
ln Vivo	The number of hematopoietic interstitial granulocytes in female C57Bl/6J mice treated with AGN 194310 (0.5 mg/kg/day; oral gavage; daily; for 10 days) is increased. Following AGN194310 therapy, there was a substantial increase in the frequency of granulocyte progenitor cells in mouse bone marrow [3].
Cell Assay	Cell Viability Assay[2] Cell Types: LNCaP, PC-3 and DU-145 cells. Tested Concentrations: 50 nM, 100 nM Incubation Duration: Experimental Results: When used together with 100 nM TTNPB, there was almost complete reversal of the growth inhibitory effect of 50 nM and partial reversal of the effect of 100 nM. Apoptosis Analysis[2] Cell Types: LNCaP cells Tested Concentrations: 1 μM Incubation Duration: 72 hrs (hours) Experimental Results: Induced apoptosis in LNCaP cells.
Animal Protocol	Animal/Disease Models: Female C57Bl/6J mice (Fiveweeks old (34-37 days))[3] Doses: 0.5 mg/kg/day Route of Administration: po (oral gavage); every day; for 10 days Experimental Results: The number of granulocytes was Dramatically increased across haemopoietic compartments. Progenitor cells containing granulocytes also increased Dramatically.
References	[1]. Synthesis and biological activity of high-affinity retinoic acid receptor antagonists. Bioorg Med Chem. 1999 Jul;7(7):1321-38. [2]. Antagonists of retinoic acid receptors (RARs) are potent growth inhibitors of prostate carcinoma cells. Br J Cancer. 2001 Aug 3;85(3):453-62. [3]. Retinoic acid receptor antagonism in vivo expands the numbers of precursor cells during granulopoiesis. Leukemia. 2002 Sep;16(9):1763-72.

Solubility Data

Solubility (In Vitro)

DMSO : 50 mg/mL (117.77 mM) H2O : 1 mg/mL (2.36 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1 mg/mL (2.36 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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 mg/mL (2.36 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.3554 mL	11.7772 mL	23.5544 mL
	5 mM	0.4711 mL	2.3554 mL	4.7109 mL
	10 mM	0.2355 mL	1.1777 mL	2.3554 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.