KAG-308 is a novel, potent, selective and orally bioactive agonist of the prostaglandin E2 receptor EP4, it selectively activated EP4 and potently inhibited tumor necrosis factor-α production in peripheral whole blood and T cells, shows a Ki and an EC50 of 2.57 nM and 17 nM for human EP4 receptor, respectively, more selective over EP1, EP2, EP3 and IP receptor. . It shows efficacy for treating ulcerative colitis and can bring about lower risk of colorectal carcinogenesis by orally bioavailable administration.

Physicochemical Properties

Molecular Formula	C24H30F2N4O3
Molecular Weight	460.516812801361
Exact Mass	460.228
CAS #	1215192-68-9
Related CAS #	1215192-68-9
PubChem CID	67108613
Appearance	White to light yellow solid powder
LogP	3.5
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	8
Heavy Atom Count	33
Complexity	722
Defined Atom Stereocenter Count	6
SMILES	FC1(/C(=C/CCCC2N=NNN=2)/O[C@H]2C[C@H]([C@H](/C=C/[C@H]([C@H](C)C3C=CC=C(C)C=3)O)[C@H]21)O)F
InChi Key	KSELABKNBIUMGG-YGBAREPYSA-N
InChi Code	InChI=1S/C24H30F2N4O3/c1-14-6-5-7-16(12-14)15(2)18(31)11-10-17-19(32)13-20-23(17)24(25,26)21(33-20)8-3-4-9-22-27-29-30-28-22/h5-8,10-12,15,17-20,23,31-32H,3-4,9,13H2,1-2H3,(H,27,28,29,30)/b11-10+,21-8-/t15-,17+,18-,19-,20+,23-/m1/s1
Chemical Name	4-[(Z)-(1S,5R,6R,7R)-6-[(1E,3R,4R)-3-Hydroxy-4-(m-tolyl)-1-pentenyl]-7-hydroxy-4,4-difluoro-2-oxabicyclo[3.3.0]octan-3-ylidene]-1-(tetrazol-5-yl)butane
Synonyms	KAG-308 KAG 308 KAG308
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.
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

KAG-308 is an oral active, powerful, selective EP4 receptor agonist that prevents colitis and encourages the healing of histological mucosa. Compared to human EP1 (Ki, 1410 nM; EC50, 1000 nM) and EP2 (Ki, 1540 nM; EC50, 1000 nM), KAG-308's Ki and EC50 values for the human EP4 receptor are 2.57 nM and 17 nM, respectively, making it more powerful. selectivity), IP receptors (Ki, 52.9 nM; EC50, >10000 nM), and EP3 (Ki, 32.4 nM; EC50, 160 nM). Dual-luciferase reporter tests demonstrate that KAG-308 possesses strong agonist action against both human and mouse EP4, with EC50 values of 0.15 nM and 1.0 nM, respectively [1].

References

[1]. KAG-308, a newly-identified EP4-selective agonist shows efficacy for treating ulcerative colitis and can bring about lower risk of colorectal carcinogenesis by oral administration. Eur J Pharmacol. 2015 May 5;754:179-89.

Solubility Data

Solubility (In Vitro)

DMSO : ~80 mg/mL (~173.72 mM) H2O : < 0.1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: 6 mg/mL (13.03 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication. 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. Solubility in Formulation 2: 6 mg/mL (13.03 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1715 mL	10.8573 mL	21.7146 mL
	5 mM	0.4343 mL	2.1715 mL	4.3429 mL
	10 mM	0.2171 mL	1.0857 mL	2.1715 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.