LIFICIGUAT

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H16N2O2
Molecular Weight	304.3425
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OCC1=CC=C(O1)C2=NN(CC3=CC=CC=C3)C4=C2C=CC=C4

InChI

InChIKey=OQQVFCKUDYMWGV-UHFFFAOYSA-N

InChI=1S/C19H16N2O2/c22-13-15-10-11-18(23-15)19-16-8-4-5-9-17(16)21(20-19)12-14-6-2-1-3-7-14/h1-11,22H,12-13H2

HIDE SMILES / InChI

Molecular Formula	C19H16N2O2
Molecular Weight	304.3425
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7527671 | https://www.ncbi.nlm.nih.gov/pubmed/9003762 | https://www.ncbi.nlm.nih.gov/pubmed/11687640 | https://www.ncbi.nlm.nih.gov/pubmed/17213816 | https://www.ncbi.nlm.nih.gov/pubmed/12671019

Lificiguat (YC-1) [3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole], a chemically synthetic benzylindazole compound, is a direct soluble guanylate cyclase activator. It possessed antiplatelet activity. YC-1 inhibits Hypoxia-inducible factor-1 (HIF-1). YC-1 demonstrated antineoplastic potential both in vitro and in vivo in animal models.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Soluble guanylate cyclase 36 Target ID: CHEMBL2111348 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11687640 \| https://www.ncbi.nlm.nih.gov/pubmed/9003762	Activator 1447
Hypoxia-inducible factor 1 alpha 17 Target ID: CHEMBL4261 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12671019 \| https://www.ncbi.nlm.nih.gov/pubmed/17213816	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 609 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12671019 https://www.ncbi.nlm.nih.gov/pubmed/24697523	Primary		Preclinical	Unknown Approved Use Unknown
Pulmonary arterial hypertension 36 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21963997	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Suppression of hypoxia inducible factor-1alpha (HIF-1alpha) by YC-1 is dependent on murine double minute 2 (Mdm2).	2006-10-06	16919599
Carbon monoxide released by CORM-3 inhibits human platelets by a mechanism independent of soluble guanylate cyclase.	2006-07-15	16713591
A domain responsible for HIF-1alpha degradation by YC-1, a novel anticancer agent.	2006-07	16773207
YC-1 induces S cell cycle arrest and apoptosis by activating checkpoint kinases.	2006-06-15	16778212
Penile erection requires association of soluble guanylyl cyclase with endothelial caveolin-1 in rat corpus cavernosum.	2006-05	16373436
Molecular mechanisms underlying rat mesenteric artery vasorelaxation induced by the nitric oxide-independent soluble guanylyl cyclase stimulators BAY 41-2272 [5-cyclopropyl-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-4-ylamine] and YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzyl Indazole].	2006-04	16352702
Sulindac independently modulates extracellular signal-regulated kinase 1/2 and cyclic GMP-dependent protein kinase signaling pathways.	2006-03	16546990
YC-1-like potentiation of NO-dependent activation of soluble guanylate cyclase by derivatives of protoporphyrin IX.	2006-03	16545073
The design and synthesis of YC-1 analogues as probes for soluble guanylate cyclase.	2006-02	16326101
YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole] inhibits neointima formation in balloon-injured rat carotid through suppression of expressions and activities of matrix metalloproteinases 2 and 9.	2006-01	16183705
Comparative relaxant effects of YC-1 and DEA/NO on the sheep sphincter of Oddi.	2006	16534245
BAY 41-2272, a potent activator of soluble guanylyl cyclase, stimulates calcium elevation and calcium-activated potassium current in pituitary GH cells.	2005-12	16445574
YC-1 suppresses constitutive nuclear factor-kappaB activation and induces apoptosis in human prostate cancer cells.	2005-10	16227413
Altered vascular reactivity in mice made hypertensive by nitric oxide synthase inhibition.	2005-10	16160594
Activation of protein kinase G up-regulates expression of 15-lipoxygenase-1 in human colon cancer cells.	2005-09-15	16166323
Interference of neutrophil-platelet interaction by YC-1: a cGMP-dependent manner on heterotypic cell-cell interaction.	2005-09-05	16112105
Enhanced responsiveness to nitric oxide, nitroxyl anions, and nitrergic transmitter by 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole in the rat anococcygeus muscle.	2005-09	15993633
Nitric oxide/cyclic guanosine monophosphate signaling in the central complex of the grasshopper brain inhibits singing behavior.	2005-07-25	15924338
Comparative relaxant effects of YC-1 and DETA/NO on spontaneous contractions and the levels of cGMP of isolated pregnant rat myometrium.	2005-07-11	15985262
YC-1-inhibited proliferation of rat mesangial cells through suppression of cyclin D1-independent of cGMP pathway and partially reversed by p38 MAPK inhibitor.	2005-07-04	15950964
Nitric oxide upregulates induction of PDGF receptor-alpha expression in rat renal mesangial cells and in anti-Thy-1 glomerulonephritis.	2005-07	15872077
YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole] inhibits endothelial cell functions induced by angiogenic factors in vitro and angiogenesis in vivo models.	2005-07	15784655
Dynamic association of nitric oxide downstream signaling molecules with endothelial caveolin-1 in rat aorta.	2005-07	15778264
The nitric oxide donor sodium nitroprusside stimulates the Na+-K+ pump in isolated rabbit cardiac myocytes.	2005-06-15	15817632
Resonance Raman and infrared spectroscopic studies of high-output forms of human soluble guanylyl cyclase.	2005-04-06	15796527
Enhancement of learning behaviour by a potent nitric oxide-guanylate cyclase activator YC-1.	2005-03	15845095
[Hypoxia-inducible factor 1: regulation, involvement in carcinogenesis and target for anticancer therapy].	2005-02	15749641
CORM-A1: a new pharmacologically active carbon monoxide-releasing molecule.	2005-02	15556971
Soluble guanylyl cyclase during postnatal porcine pulmonary maturation.	2005-01	15447938
Nerve-induced release of nitric oxide from the rabbit corpus cavernosum is modulated by cyclic guanosine 3',5'-monophosphate.	2005	15893640
The blockade of cyclopiazonic acid-induced store-operated Ca2+ entry pathway by YC-1 in neutrophils.	2004-11-15	15476676
Activation of soluble guanylyl cyclase inhibits estradiol production and cyclic AMP accumulation from cultured rat granulosa cells.	2004-10	15474089
New anticancer strategies targeting HIF-1.	2004-09-15	15313402
An evolutionarily conserved mechanism for sensitization of soluble guanylyl cyclase reveals extensive nitric oxide-mediated upregulation of cyclic GMP in insect brain.	2004-09	15341595
YC-1-induced cyclooxygenase-2 expression is mediated by cGMP-dependent activations of Ras, phosphoinositide-3-OH-kinase, Akt, and nuclear factor-kappaB in human pulmonary epithelial cells.	2004-09	15322248
Soluble guanylyl cyclase is localised in the acinar cells and participates in amylase secretion in rat parotid gland.	2004-09	15275856
Downregulation of cGMP-dependent protein kinase expression by inflammatory cytokines in vascular smooth muscle cells.	2004-07	14985234
Resonance Raman study on synergistic activation of soluble guanylate cyclase by imidazole, YC-1 and GTP.	2004-05	15134928
Versatile pharmacological actions of YC-1: anti-platelet to anticancer.	2004-04-15	15127725
Inhibition of phosphodiesterase type 5 by the activator of nitric oxide-sensitive guanylyl cyclase BAY 41-2272.	2004-04-13	15066950
Inhibitory mechanisms of YC-1 and PMC in the induction of iNOS expression by lipoteichoic acid in RAW 264.7 macrophages.	2004-04-01	15013857
Microsomal prostaglandin E synthase-1 is overexpressed in inflammatory bowel disease. Evidence for involvement of the transcription factor Egr-1.	2004-03-26	14722058
Functional characterization of nitric oxide and YC-1 activation of soluble guanylyl cyclase: structural implication for the YC-1 binding site?	2004-03-23	15023055
Antiaggregating and antithrombotic activities of new 1, 2, 3-triazolecarboxamides.	2004-03	15038061
The inhibitory mechanism of YC-1, a benzyl indazole, on smooth muscle cell proliferation: an in vitro and in vivo study.	2004-03	15037810
Involvement of the cGMP signalling pathway in the regulation of viability in insulin-secreting BRIN-BD11 cells.	2004-02-13	14960318
Analysis of nitric oxide-sensitive guanylyl cyclase in human platelets before and after aggregation.	2004-01-10	14713512
YC-1, a nitric oxide-independent activator of soluble guanylate cyclase, inhibits the spontaneous contractions of isolated pregnant rat myometrium.	2004-01	14745113
Contribution of cGMP but not peroxynitrite to negative feedback regulation of penile erection elicited by nitric oxide in the hippocampal formation of the rat.	2004-01	14654104
The NO signaling pathway differentially regulates KCC3a and KCC3b mRNA expression.	2003-11	14732340

Patents

Sample Use Guides

In Vivo Use Guide

Lificiguat (YC-1) was tested on in vivo model of pulmonary arterial hypertension. To assess preventive or therapeutic effects, randomized mice were subjected to once daily i.p. injections of YC-1 for the entire hypoxic period (5 mg/kg) or for the last seven days of a 28-day hypoxic period (5 and 10 mg/kg).

Route of Administration: Intraperitoneal

In Vitro Use Guide

25-100 uM lificiguat (YC-1) promoted G0/G1 phase arrest and provoked apoptosis in CAR cells.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 08:44:17 GMT 2025` Edited by `admin` on `Wed Apr 02 08:44:17 GMT 2025`
Record UNII	515CC1WPTE
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NSC-728165

Preferred Name

English

LIFICIGUAT

Official Name

English

lificiguat [INN]

Common Name

English

(5-(1-BENZYL-1H-INDAZOL-3-YL)FURAN-2-YL)METHANOL

Systematic Name

English

Lificiguat [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29707