Description
YC-1 (170632-47-0) is a nitric oxide-independent activator of soluble guanylyl cyclase (sGC). Significantly elevates cGMP levels and inhibits collagen-stimulated aggregation of rabbit platelets (IC50?= 14.6 μM).1?Induces human endometrial cancer cell senescence via modulation of HIF1α activity.2?Induces degradation of HIF1α.3?Protects against glutamate-induced neuronal damage4?and β-amyloid-induced toxicity in differentiated PC12 cells5.
Uses
YC-1 has been used as a hypoxia-inducible factor 1α (HIF-1α) inhibitor:
- to reduce hypoxia induced Jagged1 expression in cardiomyocytes (CMs)
- to study its effect on progenitor expansion and CD34+ and side population (SP) cell phenotype and on the proliferation rate of cells with an ability to form long term colony forming units
- to study its effect on regulating sphingosine 1-phosphate (S1P) bound to albumin induced plasminogen activator inhibitor 1 (PAI-1) expression by activating Rho/ Rho-associated protein kinase (ROCK) pathway.
Definition
ChEBI: Lificiguat is a member of the class of indazoles that is 1H-indazole which is substituted by a benzyl group at position 1 and a 5-(hydroxymethyl)-2-furyl group at position 3. It is an activator of soluble guanylate cyclase and inhibits platelet aggregation. It has a role as an antineoplastic agent, a soluble guanylate cyclase activator, an apoptosis inducer, a platelet aggregation inhibitor and a vasodilator agent. It is a member of indazoles, a member of furans and an aromatic primary alcohol.
General Description
A nitric oxide-independent, superoxide-sensitive activator of soluble guanylyl cyclase. Inhibits platelet adhesion to collagen and acts as an antithrombotic agent. Reported to reduce HIF-1α levels and xenograft growth.
Biochem/physiol Actions
YC-1 activates soluble guanylyl cyclase and prevents platelet aggregation and vascular contraction. It has a potential to treat circulation disorders. YC-1 also has an ability to inhibit hypoxia-inducible factor 1α (HIF-1α) activity in vitro. It acts as a potential antiangiogenic anticancer agent.
References
1) Martin?et al.?(2001),?YC-1 activation of human soluble guanylyl cyclase has both heme-dependent and heme-independent components;?Proc. Natl. Acad. Sci. USA,?98?12938
2) Kato?et al.?(2006),?Induction of human endometrial cancer cell senescence through modulation of HIF-1alpha activity by EGLN1; Int. J. Cancer,?118?1144
3) Kim?et al.?(2006),?A domain responsible for HIF-1alpha degradation by YC-1, a novel anticancer agent; Int. J. Oncol.,?29?255
4) Tai?et al. (2018),?Therapeutic window for YC-1 following glutamate-induced neuronal damage and transient focal cerebral ischemia; Mol. Med. Rep.,?17?6490
5) Tsai?et al.?(2013),?The role of heat shock protein 70 in the protective effect of YC-1 on β-amyloid-induced toxicity in differentiated PC12 cells.; PLoS One,?8(7)?e69320
