BAY-899 is an orally potent and specific luteinizing hormone receptor (LH-R) antagonist (inhibitor) with IC50s of 185 nM and 46 nM for hLH (human LH) and rLH (rat LH), respectively. BAY-899 can reduce sex hormone levels.

Physicochemical Properties

Molecular Formula	C25H19F2N5O2
Molecular Weight	459.45
Exact Mass	459.15
CAS #	2471967-92-5
Related CAS #	(R)-BAY-899
PubChem CID	139600336
Appearance	White to off-white solid powder
Density	1.4±0.1 g/cm3
Index of Refraction	1.657
LogP	2.81
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	4
Heavy Atom Count	34
Complexity	664
Defined Atom Stereocenter Count	1
SMILES	C1CN([C@H](C2=C1N=CC=C2)C3=CC=C(C=C3)F)C(=O)NC4=CN=C(N=C4)OC5=CC=C(C=C5)F
InChi Key	VKQBTIMLSDGNLG-QHCPKHFHSA-N
InChi Code	InChI=1S/C25H19F2N5O2/c26-17-5-3-16(4-6-17)23-21-2-1-12-28-22(21)11-13-32(23)25(33)31-19-14-29-24(30-15-19)34-20-9-7-18(27)8-10-20/h1-10,12,14-15,23H,11,13H2,(H,31,33)/t23-/m0/s1
Chemical Name	(5S)-N-[2-(4-fluorophenoxy)pyrimidin-5-yl]-5-(4-fluorophenyl)-7,8-dihydro-5H-1,6-naphthyridine-6-carboxamide
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	IC50: 185 nM (hLH) and 46nM (rLH)[1]
ln Vivo	In intact female rats, BAY-899 (oral; 12.5 mg/kg/day; for 8 days) effectively lowers blood estradiol levels[1]. The half-lives of BAY-899 (i.v., 0.5 mg/kg or po, 2 mg/kg) are 11 and 12 hours, respectively. Also, the Cmax for IV and PO is 0.24 kg/L and 0.97 kg/L, respectively[1].
Animal Protocol	Animal/Disease Models: Intact female rats[1] Doses: 12.5 mg/kg Route of Administration: Oral; for 8 days Experimental Results: demonstrated an efficiency to reduce serum estradiol levels. Animal/Disease Models: Female and male Wistar rats[1] Doses: 0.5 mg/kg of iv or 2 mg/kg of po Route of Administration: Iv or po Experimental Results: Has t1/2s of 11 hrs (hours) and 12 hrs (hours) for iv and po. And the Cmaxs are 0.97 kg/L and 0.24 kg/L for iv and po.
References	[1]. Discovery of BAY-298 and BAY-899: Tetrahydro-1,6-naphthyridine-Based, Potent and Selective Antagonists of the Luteinizing Hormone Receptor Which Reduce Sex Hormone Levels In Vivo. J Med Chem. 2019 Oct 31.

Solubility Data

Solubility (In Vitro)

DMSO: 130 mg/mL (282.95 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 3.5 mg/mL (7.62 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 35.0 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: ≥ 3.5 mg/mL (7.62 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 35.0 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. Solubility in Formulation 3: ≥ 3.5 mg/mL (7.62 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 35.0 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	2.1765 mL	10.8826 mL	21.7652 mL
	5 mM	0.4353 mL	2.1765 mL	4.3530 mL
	10 mM	0.2177 mL	1.0883 mL	2.1765 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.