PIMILPROST

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H40O5
Molecular Weight	396.5607
Optical Activity	UNSPECIFIED
Defined Stereocenters	7 / 7
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12C[C@@H](CCOCC(=O)OC)C[C@]1([H])[C@@H](\C=C\[C@@H](O)C[C@@H](C)CCCC)[C@H](O)C2

InChI

InChIKey=SLDLSMFNGFIPNI-RXYUHBJGSA-N

InChI=1S/C23H40O5/c1-4-5-6-16(2)11-19(24)7-8-20-21-13-17(12-18(21)14-22(20)25)9-10-28-15-23(26)27-3/h7-8,16-22,24-25H,4-6,9-15H2,1-3H3/b8-7+/t16-,17+,18-,19+,20+,21-,22+/m0/s1

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Description
Sources: http://adisinsight.springer.com/drugs/800003103
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/8533126 http://www.ncbi.nlm.nih.gov/pubmed/7511960 https://www.ncbi.nlm.nih.gov/pubmed/9195295

Pimilprost (SM-10902) and its free acid, SM-10906 are new stable 3-oxa-methano prostaglandin (PG) I1 analogs, SM-10902 is a prodrug of SM-10906. SM-10906, but not SM-10902 was demonstrated to be an agonist for IP receptors. SM-10906 was shown to exert its anti-platelet and vasodilatory activities through the increase of the cAMP level. Pimilprost was being developed by Dainippon Sumitomo Pharma (formerly Sumitomo Pharmaceuticals) in Japan for the treatment of skin ulcers. In Japan, an NDA was filed for pimilprost and was awaiting registration. However, development appears to have been discontinued.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Prostacyclin receptor 9 Target ID: P43252 Gene ID: 19222.0 Gene Symbol: Ptgir Target Organism: Mus musculus (Mouse) Sources: http://www.ncbi.nlm.nih.gov/pubmed/7511960	Agonist 2678		100.0 nM [IC50]
Prostanoid IP receptor 18 Target ID: CHEMBL1995 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9195295	Agonist 2678		6.3 null [pKi]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Skin ulcer 8 Sources: http://www.ncbi.nlm.nih.gov/pubmed/8790992 http://adisinsight.springer.com/drugs/800003103	Primary		Basic research	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Pharmacological properties of the new stable prostacyclin analogue 3-Oxa-methano-prostaglandin I.	1994 Apr	8011001
Prostacyclin (PGI) receptor binding and cyclic AMP synthesis activities of PGI1 analogues, SM-10906 and its methyl ester, SM-10902, in mastocytoma P-815 cells.	1994 Jan	7511960
Prostaglandin I1 analogues, SM-10902 and SM-10906, affect human keratinocytes and fibroblasts in vitro in a manner similar to PGE1: therapeutic potential for wound healing.	1995	7487139
Antiplatelet functions of a stable prostacyclin analog, SM-10906 are exerted by its inhibitory effect on inositol 1,4,5-trisphosphate production and cytosolic Ca++ increase in rat platelets stimulated by thrombin.	1995 Aug 1	8533126
Effect of topical application of a stable prostacyclin analogue, SM-10902 on wound healing in diabetic mice.	1996 Apr 29	8790992
Antithrombotic effect of topically applied 3-oxa-methano-prostaglandin I1 in the microcirculation and antiplatelet functions of its active form.	1996 Feb	8711136
Affinity for [3H]iloprost binding sites and cAMP synthesis activity of a 3-oxa-methano prostaglandin I1 analog, SM-10906, in human platelets and endothelial cells.	1997 May	9195295

Patents

Sample Use Guides

In Vivo Use Guide

genetically diabetic mice (db/db mice) treated with Pimilprost (SM-10902) ointment (1, 10 and 100 micrograms/g) showed greater decrease in wound lesion area not covered with epidermis and fewer complete healing days than those treated with ointment base

Route of Administration: Transdermal

In Vitro Use Guide

Pimilprost (SM-10902) is a prodrug of SM-10906. SM-10906 dose-dependently stimulated GTP-dependent adenylate cyclase activity in the membrane fraction, the EC50 value being 35 nM. Furthermore, SM-10906 prevented a thrombin-induced increase in the intracellular Ca2+ concentration, the IC50 value being 300 nM. These IC50 and EC50 values are much lower than those of SM-10902.

Name

Type

Language

PIMILPROST

Official Name

English

(+)-METHYL (2-((2R,3AS,4R,5-R,6AS)-OCTAHYDRO-5-HYDROXY-4-((1E,3S,5S)-3-HYDROXY-5-METHYL-1-NONENYL)-2-PENTALENYL)ETHOXY)ACETATE

Common Name

English

PIMILPROST [JAN]

Common Name

English

SM-10902

Code

English

SM10902

Code

English

pimilprost [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C78568