Olinciguat

Olinciguat
Clinical data
Other names	IW-1701
Legal status
Legal status	Investigational;
Identifiers
	IUPAC name (2R)-3,3,3-Trifluoro-2-[[[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]amino]methyl]-2-hydroxypropanamide;
CAS Number	1628732-62-6;
PubChem CID	90445883;
IUPHAR/BPS	10213;
DrugBank	DB15238;
ChemSpider	64835205;
UNII	PD5F4ZXD21;
KEGG	D11475;
ChEMBL	ChEMBL4297616;
Chemical and physical data
Formula	C21H16F5N7O3
Molar mass	509.397 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1=CC=C(C(=C1)CN2C(=CC(=N2)C3=NC=C(C(=N3)NC[C@@](C(=O)N)(C(F)(F)F)O)F)C4=NOC=C4)F;
	InChI InChI=1S/C21H16F5N7O3/c22-12-4-2-1-3-11(12)9-33-16(14-5-6-36-32-14)7-15(31-33)18-28-8-13(23)17(30-18)29-10-20(35,19(27)34)21(24,25)26/h1-8,35H,9-10H2,(H2,27,34)(H,28,29,30)/t20-/m1/s1; Key:YWQFJNWMWZMXRW-HXUWFJFHSA-N;

Olinciguat (IW-1701) is a soluble guanylate cyclase stimulator that was in development for sickle cell anemia.^[1]^[2]^[3] After receiving orphan drug status in 2018^[4] and completing a phase II trial, its development for sickle cell anemia was discontinued in 2020.^[5]

References

^ Buys, E. S.; Zimmer, D. P.; Chickering, J.; Graul, R.; Chien, Y. T.; Profy, A.; Hadcock, J. R.; Masferrer, J. L.; Milne, G. T. (1 August 2018). "Discovery and development of next generation sGC stimulators with diverse multidimensional pharmacology and broad therapeutic potential". Nitric Oxide. 78: 72–80. doi:10.1016/j.niox.2018.05.009. ISSN 1089-8603. PMID 29859918. S2CID 44149174.
^ Tchernychev, Boris; Li, Huihui; Lee, Sung-Kyun; Gao, Xin; Ramanarasimhaiah, Raghunath; Liu, Guang; Hall, Katherine C.; Bernier, Sylvie G.; Jones, Juli E.; Feil, Susanne; Feil, Robert; Buys, Emmanuel S.; Graul, Regina M.; Frenette, Paul S.; Masferrer, Jaime L. (September 2021). "Olinciguat, a stimulator of soluble guanylyl cyclase, attenuates inflammation, vaso-occlusion and nephropathy in mouse models of sickle cell disease". British Journal of Pharmacology. 178 (17): 3463–3475. doi:10.1111/bph.15492. ISSN 1476-5381. PMC 8453770. PMID 33864386.
^ Zimmer, Daniel P.; Shea, Courtney M.; Tobin, Jenny V.; Tchernychev, Boris; Germano, Peter; Sykes, Kristie; Banijamali, Ali R.; Jacobson, Sarah; Bernier, Sylvie G.; Sarno, Renee; Carvalho, Andrew; Chien, Yueh-tyng; Graul, Regina; Buys, Emmanuel S.; Jones, Juli E.; Wakefield, James D.; Price, Gavrielle M.; Chickering, Jennifer G.; Milne, G. Todd; Currie, Mark G.; Masferrer, Jaime L. (8 April 2020). "Olinciguat, an Oral sGC Stimulator, Exhibits Diverse Pharmacology Across Preclinical Models of Cardiovascular, Metabolic, Renal, and Inflammatory Disease". Frontiers in Pharmacology. 11: 419. doi:10.3389/fphar.2020.00419. ISSN 1663-9812. PMC 7156612. PMID 32322204.
^ "Ironwood Pharmaceuticals Announces FDA Orphan Drug Designation for Olinciguat for the Treatment of Sickle Cell Disease". investor.ironwoodpharma.com. Retrieved 8 November 2023.
^ PhD, Joana Carvalho (20 October 2020). "Cyclerion Suspends Development of Olinciguat for Sickle Cell Disease". sicklecellanemianews.com. Retrieved 8 November 2023.

[1] Buys, E. S.; Zimmer, D. P.; Chickering, J.; Graul, R.; Chien, Y. T.; Profy, A.; Hadcock, J. R.; Masferrer, J. L.; Milne, G. T. (1 August 2018). "Discovery and development of next generation sGC stimulators with diverse multidimensional pharmacology and broad therapeutic potential". Nitric Oxide. 78: 72–80. doi:10.1016/j.niox.2018.05.009. ISSN 1089-8603. PMID 29859918. S2CID 44149174.

[2] Tchernychev, Boris; Li, Huihui; Lee, Sung-Kyun; Gao, Xin; Ramanarasimhaiah, Raghunath; Liu, Guang; Hall, Katherine C.; Bernier, Sylvie G.; Jones, Juli E.; Feil, Susanne; Feil, Robert; Buys, Emmanuel S.; Graul, Regina M.; Frenette, Paul S.; Masferrer, Jaime L. (September 2021). "Olinciguat, a stimulator of soluble guanylyl cyclase, attenuates inflammation, vaso-occlusion and nephropathy in mouse models of sickle cell disease". British Journal of Pharmacology. 178 (17): 3463–3475. doi:10.1111/bph.15492. ISSN 1476-5381. PMC 8453770. PMID 33864386.

[3] Zimmer, Daniel P.; Shea, Courtney M.; Tobin, Jenny V.; Tchernychev, Boris; Germano, Peter; Sykes, Kristie; Banijamali, Ali R.; Jacobson, Sarah; Bernier, Sylvie G.; Sarno, Renee; Carvalho, Andrew; Chien, Yueh-tyng; Graul, Regina; Buys, Emmanuel S.; Jones, Juli E.; Wakefield, James D.; Price, Gavrielle M.; Chickering, Jennifer G.; Milne, G. Todd; Currie, Mark G.; Masferrer, Jaime L. (8 April 2020). "Olinciguat, an Oral sGC Stimulator, Exhibits Diverse Pharmacology Across Preclinical Models of Cardiovascular, Metabolic, Renal, and Inflammatory Disease". Frontiers in Pharmacology. 11: 419. doi:10.3389/fphar.2020.00419. ISSN 1663-9812. PMC 7156612. PMID 32322204.

[4] "Ironwood Pharmaceuticals Announces FDA Orphan Drug Designation for Olinciguat for the Treatment of Sickle Cell Disease". investor.ironwoodpharma.com. Retrieved 8 November 2023.

[5] PhD, Joana Carvalho (20 October 2020). "Cyclerion Suspends Development of Olinciguat for Sickle Cell Disease". sicklecellanemianews.com. Retrieved 8 November 2023.

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