Lificiguat
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MedKoo CAT#: 406116

CAS#: 170632-47-0

Description: Lificiguat, also known as YC-1, is a inhibitor of Hypoxia-inducible factor-1alpha (HIF-1alpha). YC-1 is widely used as a potent inhibitor of HIF-1alpha both in vitro and in vivo, and is also being developed as a novel anticancer drug. YC-1 effectively inhibits tumor invasion and metastasis, and imply that YC-1 is worth while to further develop as a multipurpose anticancer drug.


Chemical Structure

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Lificiguat
CAS# 170632-47-0

Theoretical Analysis

MedKoo Cat#: 406116
Name: Lificiguat
CAS#: 170632-47-0
Chemical Formula: C19H16N2O2
Exact Mass: 304.12118
Molecular Weight: 304.34
Elemental Analysis: C, 74.98; H, 5.30; N, 9.20; O, 10.51

Price and Availability

Size Price Availability Quantity
25.0mg USD 150.0 Same day
50.0mg USD 250.0 Same day
100.0mg USD 450.0 Same day
500.0mg USD 1750.0 Same day
1.0g USD 2250.0 Same day
2.0g USD 3650.0 Same day
5.0g USD 4650.0 2 Weeks
10.0g USD 6950.0 2 Weeks
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Synonym: YC1; YC 1; YC-1; Lificiguat.

IUPAC/Chemical Name: 5-​[1-​(phenylmethyl)-​1H-​indazol-​3-​yl]-​2-​furanmethanol

InChi Key: OQQVFCKUDYMWGV-UHFFFAOYSA-N

InChi Code: 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

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

Appearance: white 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, not in water

Shelf Life: >2 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: 2934.99.9001

Biological target: Lificiguat binds to the β subunit of soluble guanylyl cyclase(sGC) with Kd of 0.6-1.1 μM in the presence of CO.
In vitro activity: To further examine the role of YC-1 in the regulation of Wnt signaling, HCC cells were treated with the IC50 of YC-1. The effect of YC-1 on Wnt signaling was evaluated by STF luciferase reporter assays. YC-1 significantly decreased the transcriptional activity of TOPflash but not that of the negative control FOPflash in HepG2, Huh6 and Hep3B cells (Figure 2A). Cyclin D1 is the downstream gene of the Wnt signaling pathway [8,19]. Subsequently, we confirmed that YC-1 decreased the expression of cyclin D1 in HepG2, Huh6 and Hep3B cells in a time-dependent manner (Figure 2B). Considering the above results, this suggests that YC-1 effectively reduces the expression of cyclin D1 through the attenuation of Wnt signaling activation, thereby suppressing tumor cell proliferation. Cancers (Basel). 2019 May; 11(5): 661. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562864/
In vivo activity: The aim of this study was to investigate the effects of a potent nitric oxide-guanylate cyclase activator, 3-(5'-hydroxymethyl-2'-furyl)1-benzylindazole (YC-1), on learning and memory functions in aged rats. Rats were divided into 2 groups as 4-month-old and 24month-old rats. Rats received YC-1 (1 mg/kg/day) for 2 weeks long-term. There was a significant change in retention latency between the groups (1-way ANOVA, F(4,45)=45.61, p<0.0001, Figure 4). Post-hoc comparisons showed that retention latency of 24-monthold aged rats was significantly shortened compared to 4-month-old young rats (p<0.0001, Dunnett’s test) and YC-1-treated 24-monthold rats (p<0.0001, Dunnett’s test) (Figure 4). The shortened retention latency scores caused by aging is reversed with the administration of YC-1 to aged rats (p<0.0001, Dunnett’s test). Foot-shock sensitivity results suggest that neither aging nor YC-1 treatment caused gross motor disabilities at testing (Figure 6). The results suggest that improvement of age-related learning and memory deficits via chronic YC-1 treatment may result from the direct effects of YC-1 on sGC. Med Sci Monit Basic Res. 2014; 20: 130–137. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4148360/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 53.0 174.15
Ethanol 22.0 72.53

Preparing Stock Solutions

The following data is based on the product molecular weight 304.34 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: 1. Wu JY, Shih YL, Lin SP, Hsieh TY, Lin YW. YC-1 Antagonizes Wnt/β-Catenin Signaling Through the EBP1 p42 Isoform in Hepatocellular Carcinoma. Cancers (Basel). 2019 May 13;11(5):661. doi: 10.3390/cancers11050661. PMID: 31086087; PMCID: PMC6562864. 2. Hsieh KY, Wei CK, Wu CC. YC-1 Prevents Tumor-Associated Tissue Factor Expression and Procoagulant Activity in Hypoxic Conditions by Inhibiting p38/NF-κB Signaling Pathway. Int J Mol Sci. 2019 Jan 9;20(2):244. doi: 10.3390/ijms20020244. PMID: 30634531; PMCID: PMC6359014. 3. Yan Z, An J, Shang Q, Zhou N, Ma J. YC-1 Inhibits VEGF and Inflammatory Mediators Expression on Experimental Central Retinal Vein Occlusion in Rhesus Monkey. Curr Eye Res. 2018 Apr;43(4):526-533. doi: 10.1080/02713683.2018.1426102. Epub 2018 Jan 24. PMID: 29364731 4. Komsuoglu Celikyurt I, Utkan T, Ozer C, Gacar N, Aricioglu F. Effects of YC-1 on learning and memory functions of aged rats. Med Sci Monit Basic Res. 2014 Aug 21;20:130-7. doi: 10.12659/MSMBR.891064. PMID: 25144469; PMCID: PMC4148360.
In vitro protocol: 1. Wu JY, Shih YL, Lin SP, Hsieh TY, Lin YW. YC-1 Antagonizes Wnt/β-Catenin Signaling Through the EBP1 p42 Isoform in Hepatocellular Carcinoma. Cancers (Basel). 2019 May 13;11(5):661. doi: 10.3390/cancers11050661. PMID: 31086087; PMCID: PMC6562864. 2. Hsieh KY, Wei CK, Wu CC. YC-1 Prevents Tumor-Associated Tissue Factor Expression and Procoagulant Activity in Hypoxic Conditions by Inhibiting p38/NF-κB Signaling Pathway. Int J Mol Sci. 2019 Jan 9;20(2):244. doi: 10.3390/ijms20020244. PMID: 30634531; PMCID: PMC6359014.
In vivo protocol: 1. Yan Z, An J, Shang Q, Zhou N, Ma J. YC-1 Inhibits VEGF and Inflammatory Mediators Expression on Experimental Central Retinal Vein Occlusion in Rhesus Monkey. Curr Eye Res. 2018 Apr;43(4):526-533. doi: 10.1080/02713683.2018.1426102. Epub 2018 Jan 24. PMID: 29364731. 2. Komsuoglu Celikyurt I, Utkan T, Ozer C, Gacar N, Aricioglu F. Effects of YC-1 on learning and memory functions of aged rats. Med Sci Monit Basic Res. 2014 Aug 21;20:130-7. doi: 10.12659/MSMBR.891064. PMID: 25144469; PMCID: PMC4148360.

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1: Tsui L, Fong TH, Wang IJ. The effect of 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) on cell viability under hypoxia. Mol Vis. 2013 Nov 16;19:2260-73. eCollection 2013. PubMed PMID: 24265542; PubMed Central PMCID: PMC3834593.

2: Carroll CE, Liang Y, Benakanakere I, Besch-Williford C, Hyder SM. The anticancer agent YC-1 suppresses progestin-stimulated VEGF in breast cancer cells and arrests breast tumor development. Int J Oncol. 2013 Jan;42(1):179-87. doi: 10.3892/ijo.2012.1675. Epub 2012 Oct 24. PubMed PMID: 23123638; PubMed Central PMCID: PMC3583650.

3: Tsui L, Fong TH, Wang IJ. YC-1 targeting of hypoxia-inducible factor-1α reduces RGC-5 cell viability and inhibits cell proliferation. Mol Vis. 2012;18:1594-603. Epub 2012 Jun 15. PubMed PMID: 22736948; PubMed Central PMCID: PMC3380911.

4: Cheng Y, Li W, Liu Y, Cheng HC, Ma J, Qiu L. YC-1 exerts inhibitory effects on MDA-MB-468 breast cancer cells by targeting EGFR in vitro and in vivo under normoxic condition. Chin J Cancer. 2012 May;31(5):248-56. doi: 10.5732/cjc.011.10383. Epub 2012 Apr 13. PubMed PMID: 22507221; PubMed Central PMCID: PMC3777523.

5: Yan J, Zhou B, Taheri S, Shi H. Differential effects of HIF-1 inhibition by YC-1 on the overall outcome and blood-brain barrier damage in a rat model of ischemic stroke. PLoS One. 2011;6(11):e27798. doi: 10.1371/journal.pone.0027798. Epub 2011 Nov 16. PubMed PMID: 22110762; PubMed Central PMCID: PMC3218033.

6: Li Y, Zhao X, Tang H, Zhong Z, Zhang L, Xu R, Li S, Wang Y. Effects of YC-1 on hypoxia-inducible factor 1 alpha in hypoxic human bladder transitional carcinoma cell line T24 cells. Urol Int. 2012;88(1):95-101. doi: 10.1159/000331881. Epub 2011 Oct 25. PubMed PMID: 22041818.

7: Liu H, Li M, Wang P, Wang F. Blockade of hypoxia-inducible factor-1α by YC-1 attenuates interferon-γ and tumor necrosis factor-α-induced intestinal epithelial barrier dysfunction. Cytokine. 2011 Dec;56(3):581-8. doi: 10.1016/j.cyto.2011.08.023. Epub 2011 Sep 3. PubMed PMID: 21890376.

8: Feng Y, Zhu H, Ling T, Hao B, Zhang G, Shi R. Effects of YC-1 targeting hypoxia-inducible factor 1 alpha in oesophageal squamous carcinoma cell line Eca109 cells. Cell Biol Int. 2011 May;35(5):491-7. doi: 10.1042/CBI20090419. PubMed PMID: 20977428.

9: DeNiro M, Al-Halafi A, Al-Mohanna FH, Alsmadi O, Al-Mohanna FA. Pleiotropic effects of YC-1 selectively inhibit pathological retinal neovascularization and promote physiological revascularization in a mouse model of oxygen-induced retinopathy. Mol Pharmacol. 2010 Mar;77(3):348-67. doi: 10.1124/mol.109.061366. Epub 2009 Dec 14. PubMed PMID: 20008515.

10: Moon SY, Chang HW, Roh JL, Kim GC, Choi SH, Lee SW, Cho KJ, Nam SY, Kim SY. Using YC-1 to overcome the radioresistance of hypoxic cancer cells. Oral Oncol. 2009 Oct;45(10):915-9. doi: 10.1016/j.oraloncology.2009.04.005. Epub 2009 May 19. PubMed PMID: 19457706.

11: Wang SX, Pei ZZ, Wu XH, Li JK, Yang YJ. [Effect of YC-1 on HIF-1 alpha and VEGF expression in human hepatocarcinoma cell lines]. Zhonghua Gan Zang Bing Za Zhi. 2009 Apr;17(4):308-9. Chinese. PubMed PMID: 19403034.

12: Li SH, Shin DH, Chun YS, Lee MK, Kim MS, Park JW. A novel mode of action of YC-1 in HIF inhibition: stimulation of FIH-dependent p300 dissociation from HIF-1{alpha}. Mol Cancer Ther. 2008 Dec;7(12):3729-38. doi: 10.1158/1535-7163.MCT-08-0074. PubMed PMID: 19074848.

13: Song SJ, Chung H, Yu HG. Inhibitory effect of YC-1, 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole, on experimental choroidal neovascularization in rat. Ophthalmic Res. 2008;40(1):35-40. Epub 2007 Nov 20. PubMed PMID: 18032914.

14: Yeh WL, Lu DY, Lin CJ, Liou HC, Fu WM. Inhibition of hypoxia-induced increase of blood-brain barrier permeability by YC-1 through the antagonism of HIF-1alpha accumulation and VEGF expression. Mol Pharmacol. 2007 Aug;72(2):440-9. Epub 2007 May 18. PubMed PMID: 17513385.

15: Shin DH, Kim JH, Jung YJ, Kim KE, Jeong JM, Chun YS, Park JW. Preclinical evaluation of YC-1, a HIF inhibitor, for the prevention of tumor spreading. Cancer Lett. 2007 Sep 18;255(1):107-16. Epub 2007 May 14. PubMed PMID: 17502124.

16: Zhao Q, Du J, Gu H, Teng X, Zhang Q, Qin H, Liu N. Effects of YC-1 on hypoxia-inducible factor 1-driven transcription activity, cell proliferative vitality, and apoptosis in hypoxic human pancreatic cancer cells. Pancreas. 2007 Mar;34(2):242-7. PubMed PMID: 17312464.

17: Sun HL, Liu YN, Huang YT, Pan SL, Huang DY, Guh JH, Lee FY, Kuo SC, Teng CM. YC-1 inhibits HIF-1 expression in prostate cancer cells: contribution of Akt/NF-kappaB signaling to HIF-1alpha accumulation during hypoxia. Oncogene. 2007 Jun 7;26(27):3941-51. Epub 2007 Jan 8. PubMed PMID: 17213816.

18: Du J, Zhao Q, Gu H, Teng XL, Qin H, Liu NZ. [Inhibitory effect of YC-1 on induction of VEGF and GPI genes in hypoxic human pancreatic cancer cells]. Zhonghua Zhong Liu Za Zhi. 2006 Jul;28(7):486-9. Chinese. PubMed PMID: 17147109.

19: Lau CK, Yang ZF, Lam CT, Tam KH, Poon RT, Fan ST. Suppression of hypoxia inducible factor-1alpha (HIF-1alpha) by YC-1 is dependent on murine double minute 2 (Mdm2). Biochem Biophys Res Commun. 2006 Oct 6;348(4):1443-8. Epub 2006 Aug 11. PubMed PMID: 16919599.

20: Yeo EJ, Ryu JH, Chun YS, Cho YS, Jang IJ, Cho H, Kim J, Kim MS, Park JW. YC-1 induces S cell cycle arrest and apoptosis by activating checkpoint kinases. Cancer Res. 2006 Jun 15;66(12):6345-52. PubMed PMID: 16778212.



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