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MedKoo Cat#: 555277 | Name: PCO371
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

PCO371 is a potent and selective PTHR1 agonist for the treatment of hypoparathyroidism. Oral administration of 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.

Chemical Structure

PCO371
PCO371
CAS#1613373-33-3

Theoretical Analysis

MedKoo Cat#: 555277

Name: PCO371

CAS#: 1613373-33-3

Chemical Formula: C29H32F3N5O6S

Exact Mass: 635.2025

Molecular Weight: 635.66

Elemental Analysis: C, 54.80; H, 5.07; F, 8.97; N, 11.02; O, 15.10; S, 5.04

Price and Availability

Size Price Availability Quantity
5mg USD 350.00 2 Weeks
10mg USD 600.00 2 Weeks
50mg USD 1,650.00 2 Weeks
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Related CAS #
No Data
Synonym
PCO371; PCO-371; PCO 371.
IUPAC/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
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)
SMILES Code
O=C1NC(C(C)(C)N1C2=CC(C)=C(CCS(=O)(N(CC3)CCC3(N=C(C4=CC=C(OC(F)(F)F)C=C4)N5)C5=O)=O)C(C)=C2)=O
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.03.00
More Info
Parathyroid hormone (PTH) is essential for calcium homeostasis and its action is mediated by the PTH type 1 receptor (PTHR1), a class B G-protein-coupled receptor. Hypoparathyroidism and osteoporosis can be treated with PTH injections; however, no orally effective PTH analogue is available.
Product Data
Product Data
Instruction
View handling instruction
Biological target:
PCO371 is an orally active full agonist of parathyroid hormone receptor 1 (PTHR1).
In vitro activity:
TBD
In vivo activity:
Oral administration of 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. These results strongly suggest that PCO371 can provide a new treatment option for PTH-related disorders, including hypoparathyroidism. Reference: Nat Commun. 2016 Nov 18;7:13384. https://pubmed.ncbi.nlm.nih.gov/27857062/
Solvent mg/mL mM
Solubility
DMSO 100.0 157.32
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 635.66 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
Tamura T, Noda H, Joyashiki E, Hoshino M, Watanabe T, Kinosaki M, Nishimura Y, Esaki T, Ogawa K, Miyake T, Arai S, Shimizu M, Kitamura H, Sato H, Kawabe Y. Identification of an orally active small-molecule PTHR1 agonist for the treatment of hypoparathyroidism. Nat Commun. 2016 Nov 18;7:13384. doi: 10.1038/ncomms13384. PMID: 27857062; PMCID: PMC5120204.
In vitro protocol:
TBD
In vivo protocol:
Tamura T, Noda H, Joyashiki E, Hoshino M, Watanabe T, Kinosaki M, Nishimura Y, Esaki T, Ogawa K, Miyake T, Arai S, Shimizu M, Kitamura H, Sato H, Kawabe Y. Identification of an orally active small-molecule PTHR1 agonist for the treatment of hypoparathyroidism. Nat Commun. 2016 Nov 18;7:13384. doi: 10.1038/ncomms13384. PMID: 27857062; PMCID: PMC5120204.
1: Nishimura Y, Esaki T, Isshiki Y, Furuta Y, Emura T, Watanabe Y, Ohta M, Arai S, Noda H, Shimizu M, Tamura T, Sato H. Synthesis and Biological Evaluations of Novel Human Parathyroid Hormone 1 Receptor (hPTHR1) Agonists Bearing Bicyclic Aromatic Moiety. ChemMedChem. 2024 Mar 1;19(5):e202300589. doi: 10.1002/cmdc.202300589. Epub 2024 Feb 5. PMID: 38273777. 2: Zhao LH, He Q, Yuan Q, Gu Y, He X, Shan H, Li J, Wang K, Li Y, Hu W, Wu K, Shen J, Xu HE. Conserved class B GPCR activation by a biased intracellular agonist. Nature. 2023 Sep;621(7979):635-641. doi: 10.1038/s41586-023-06467-w. Epub 2023 Jul 31. PMID: 37524305. 3: Kobayashi K, Kawakami K, Kusakizako T, Tomita A, Nishimura M, Sawada K, Okamoto HH, Hiratsuka S, Nakamura G, Kuwabara R, Noda H, Muramatsu H, Shimizu M, Taguchi T, Inoue A, Murata T, Nureki O. Class B1 GPCR activation by an intracellular agonist. Nature. 2023 Jun;618(7967):1085-1093. doi: 10.1038/s41586-023-06169-3. Epub 2023 Jun 7. PMID: 37286611; PMCID: PMC10307627. 4: Nishimura Y, Esaki T, Isshiki Y, Furuta Y, Mizutani A, Kotake T, Emura T, Watanabe Y, Ohta M, Nakagawa T, Ogawa K, Arai S, Noda H, Kitamura H, Shimizu M, Tamura T, Sato H. Lead Optimization and Avoidance of Reactive Metabolite Leading to PCO371, a Potent, Selective, and Orally Available Human Parathyroid Hormone Receptor 1 (hPTHR1) Agonist. J Med Chem. 2020 May 28;63(10):5089-5099. doi: 10.1021/acs.jmedchem.9b01743. Epub 2020 Feb 17. PMID: 32022560. 5: Tamura T, Noda H, Joyashiki E, Hoshino M, Watanabe T, Kinosaki M, Nishimura Y, Esaki T, Ogawa K, Miyake T, Arai S, Shimizu M, Kitamura H, Sato H, Kawabe Y. Identification of an orally active small-molecule PTHR1 agonist for the treatment of hypoparathyroidism. Nat Commun. 2016 Nov 18;7:13384. doi: 10.1038/ncomms13384. PMID: 27857062; PMCID: PMC5120204.