PCO371 (PCO-371; PCO 371) is a novel, potent, selective and orally bioactive PTHR1 (parathyroid hormone receptor 1) full agonist potentially for the treatment of hypoparathyroidism. Orally administrating PCO371 to osteopenic rats provokes a significant increase in bone turnover with limited increase in bone mass. In hypocalcemic rats, PCO371 restores serum calcium levels without increasing urinary calcium, and with stronger and longer-lasting effects than PTH injections.

Physicochemical Properties

Molecular Formula	C29H32F3N5O6S
Molecular Weight	635.654496192932
Exact Mass	635.202
CAS #	1613373-33-3
PubChem CID	76283707
Appearance	White to off-white solid powder
Density	1.5±0.1 g/cm3
Index of Refraction	1.636
LogP	4.56
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	7
Heavy Atom Count	44
Complexity	1270
Defined Atom Stereocenter Count	0
InChi Key	LDZJFVOUPUFOHX-UHFFFAOYSA-N
InChi Code	InChI=1S/C29H32F3N5O6S/c1-17-15-20(37-26(40)34-24(38)27(37,3)4)16-18(2)22(17)9-14-44(41,42)36-12-10-28(11-13-36)25(39)33-23(35-28)19-5-7-21(8-6-19)43-29(30,31)32/h5-8,15-16H,9-14H2,1-4H3,(H,33,35,39)(H,34,38,40)
Chemical Name	1-(3,5-dimethyl-4-(2-((4-oxo-2-(4-(trifluoromethoxy)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-8-yl)sulfonyl)ethyl)phenyl)-5,5-dimethylimidazolidine-2,4-dione
Synonyms	PCO371 PCO-371 PCO 371.
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	Orally administered PCO371 is a complete agonist that is active on parathyroid hormone receptor 1 (PTHR1) and does not bind to PTH 2 receptors. With an EC50 of 2.4 μM in COS-7 cells expressing hPTHR1 and 2.5 μM in COS-7 cells transfected with hPTHR1-delNT, PCO371 promotes the generation of cAMP and increases phospholipase C activity (EC50, 17 μM) [1].
References	[1]. Identification of an orally active small-molecule PTHR1 agonist for the treatment of hypoparathyroidism. Nat Commun. 2016 Nov 18;7:13384.
Additional Infomation	PCO-371 is under investigation in clinical trial NCT02475616 (A Single Ascending Dose Study of PCO371 in Healthy Volunteers).

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~157.32 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 6.25 mg/mL (9.83 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 62.5 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: ≥ 6.25 mg/mL (9.83 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 62.5 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: ≥ 6.25 mg/mL (9.83 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 62.5 mg/mL clear DMSO stock solution to 900 μL 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	1.5732 mL	7.8660 mL	15.7319 mL
	5 mM	0.3146 mL	1.5732 mL	3.1464 mL
	10 mM	0.1573 mL	0.7866 mL	1.5732 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.