iCRT14
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 555248

CAS#: 677331-12-3

Description: iCRT14 is a potent inhibitor of β-catenin-responsive transcription (CRT) that inhibits Wnt signaling in a reporter assay in vitro (IC50 = 40.3 nM). It inhibits the interaction between β-catenin and T cell factor 4 (Tcf4) in quantitative reporter assays of β-catenin/Tcf4 binding (Ki = 53.51 μM).

Chemical Structure

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iCRT14
CAS# 677331-12-3
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 555248
Name: iCRT14
CAS#: 677331-12-3
Chemical Formula: C21H17N3O2S
Exact Mass: 375.10
Molecular Weight: 375.446
Elemental Analysis: C, 67.18; H, 4.56; N, 11.19; O, 8.52; S, 8.54

Price and Availability

Size Price Availability Quantity
25mg USD 150 Ready to ship
50mg USD 250 Ready to ship
100mg USD 450 Ready to ship
200mg USD 750 Ready to ship
500mg USD 1350 Ready to ship
1g USD 2450 Ready to ship
2g USD 4250 2 weeks
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Synonym: iCRT14; iCRT-14; iCRT 14; Wnt inhibitor;

IUPAC/Chemical Name: 5-[[2,5-dimethyl-1-(3-pyridinyl)-1H-pyrrol-3-yl]methylene]-3-phenyl-2,4-thiazolidinedione

InChi Key: NCSHZXNGQYSKLR-XDHOZWIPSA-N

InChi Code: InChI=1S/C21H17N3O2S/c1-14-11-16(15(2)23(14)18-9-6-10-22-13-18)12-19-20(25)24(21(26)27-19)17-7-4-3-5-8-17/h3-13H,1-2H3/b19-12+

SMILES Code: O=C(N(C1=CC=CC=C1)C/2=O)SC2=C\C3=C(C)N(C4=CC=CN=C4)C(C)=C3

Appearance: 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

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

More Info:

Biological target: iCRT 14 is a novel potent inhibitor of β-catenin-responsive transcription (CRT), with IC50 of 40.3 nM against Wnt responsive STF16 luciferase.
In vitro activity: To investigate the effectiveness of five different compounds targeting the Wnt pathway in breast cancer cells, the inhibitory effects of iCRT-14 on cell proliferation were tested in BT-549, MDA-MB-231, HCC-1143 and HCC-1937 cell lines using the xCELLigence system that allows continuous and quantitative monitoring of cell status in real-time. Cells were treated with increasing concentrations and assayed for 48 hours. The concentration range for treatment with each inhibitor was determined based on previous studies. This analysis showed that it induced differential effects on proliferation of these TNBC cells in a dose- and time-dependent manner (Figure 3; see Additional file 4: Figure S3, Additional file 5: Figure S4 and Additional file 6: Figure S5). These findings were confirmed using an alternative cell viability assay, the Cell Titer-Glo luminescent cell viability assay (see Additional file 7: Figure S6). Reference: J Transl Med. 2013 Nov 4;11:280. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24188694/
In vivo activity: The HCT116 and HT29 xenograft models were chosen: both of these result in rapidly proliferating tumors when implanted s.c. in athymic nude mice. After measurable tumors of at least 80–120 mm3 volume were established, the animals were administered iCRT14 (dissolved in DMSO) at a concentration of 50 mg/kg. The compound was administered by i.p. injection three times a week for 3 wk. Immunostaining of xenograft sections after different time periods revealed a marked decrease in CycD1 compared with DMSO-treated controls (Fig. S5 A and B). This coincided with reduced proliferation of the tumors, reflected by fewer numbers of cells staining positive for phospho-histone3 in drug-treated tumors (Fig. S5 C and D); similar results were seen in HT29 xenografts (Fig. S5 E–H). Furthermore, these effects were correlated with a marked reduction (∼50%) in the initial growth rate of tumors within the first 3 wk (∼day 19) of compound administration (Fig. S5 I and J). After day 19, however, the rate of tumor growth was comparable with that of DMSO-treated control. Administration of a lower concentration of compound (20 mg/kg) by minipump also resulted in identical effects in HCT116 xenografts (Fig. S5I). Importantly, throughout the course of the study, the mice did not display any signs of systemic toxicity or weight loss that would indicate off-target or nonspecific effects. Reference: Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):5954-63. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21393571/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 37.0 98.55

Preparing Stock Solutions

The following data is based on the product molecular weight 375.45 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:
In vitro protocol: 1. Gonsalves FC, Klein K, Carson BB, Katz S, Ekas LA, Evans S, Nagourney R, Cardozo T, Brown AM, DasGupta R. An RNAi-based chemical genetic screen identifies three small-molecule inhibitors of the Wnt/wingless signaling pathway. Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):5954-63. doi: 10.1073/pnas.1017496108. Epub 2011 Mar 10. PMID: 21393571; PMCID: PMC3076864. 2. Bilir B, Kucuk O, Moreno CS. Wnt signaling blockage inhibits cell proliferation and migration, and induces apoptosis in triple-negative breast cancer cells. J Transl Med. 2013 Nov 4;11:280. doi: 10.1186/1479-5876-11-280. PMID: 24188694; PMCID: PMC4228255.
In vivo protocol: 1. Gonsalves FC, Klein K, Carson BB, Katz S, Ekas LA, Evans S, Nagourney R, Cardozo T, Brown AM, DasGupta R. An RNAi-based chemical genetic screen identifies three small-molecule inhibitors of the Wnt/wingless signaling pathway. Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):5954-63. doi: 10.1073/pnas.1017496108. Epub 2011 Mar 10. PMID: 21393571; PMCID: PMC3076864.

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1: More S, Yang X, Zhu Z, Bamunuarachchi G, Guo Y, Huang C, Bailey K, Metcalf JP, Liu L. Regulation of influenza virus replication by Wnt/β-catenin signaling. PLoS One. 2018 Jan 11;13(1):e0191010. doi: 10.1371/journal.pone.0191010. eCollection 2018. PubMed PMID: 29324866; PubMed Central PMCID: PMC5764324.

2: Gufler S, Artes B, Bielen H, Krainer I, Eder MK, Falschlunger J, Bollmann A, Ostermann T, Valovka T, Hartl M, Bister K, Technau U, Hobmayer B. β-Catenin acts in a position-independent regeneration response in the simple eumetazoan Hydra. Dev Biol. 2018 Jan 15;433(2):310-323. doi: 10.1016/j.ydbio.2017.09.005. Epub 2017 Nov 3. PubMed PMID: 29108673.

3: Zhang JL, Liu Y, Yang H, Zhang HQ, Tian XX, Fang WG. ATP-P2Y2-β-catenin axis promotes cell invasion in breast cancer cells. Cancer Sci. 2017 Jul;108(7):1318-1327. doi: 10.1111/cas.13273. Epub 2017 Jun 6. PubMed PMID: 28474758; PubMed Central PMCID: PMC5497932.

4: Zhu L, Thunuguntla P, Liu Y, Hancock M, Jones C. The β-catenin signaling pathway stimulates bovine herpesvirus 1 productive infection. Virology. 2017 Jan;500:91-95. doi: 10.1016/j.virol.2016.10.014. Epub 2016 Oct 24. PubMed PMID: 27788397.

5: Mathur R, Sehgal L, Braun FK, Berkova Z, Romaguerra J, Wang M, Rodriguez MA, Fayad L, Neelapu SS, Samaniego F. Targeting Wnt pathway in mantle cell lymphoma-initiating cells. J Hematol Oncol. 2015 Jun 6;8:63. doi: 10.1186/s13045-015-0161-1. PubMed PMID: 26048374; PubMed Central PMCID: PMC4460883.

6: Chen ZL, Shao WJ, Xu F, Liu L, Lin BS, Wei XH, Song ZL, Lu HG, Fantus IG, Weng JP, Jin TR. Acute Wnt pathway activation positively regulates leptin gene expression in mature adipocytes. Cell Signal. 2015 Mar;27(3):587-97. doi: 10.1016/j.cellsig.2014.12.012. Epub 2014 Dec 27. PubMed PMID: 25550093.

7: Dere R, Perkins AL, Bawa-Khalfe T, Jonasch D, Walker CL. β-catenin links von Hippel-Lindau to aurora kinase A and loss of primary cilia in renal cell carcinoma. J Am Soc Nephrol. 2015 Mar;26(3):553-64. doi: 10.1681/ASN.2013090984. Epub 2014 Oct 13. PubMed PMID: 25313256; PubMed Central PMCID: PMC4341469.

8: Dandekar S, Romanos-Sirakis E, Pais F, Bhatla T, Jones C, Bourgeois W, Hunger SP, Raetz EA, Hermiston ML, Dasgupta R, Morrison DJ, Carroll WL. Wnt inhibition leads to improved chemosensitivity in paediatric acute lymphoblastic leukaemia. Br J Haematol. 2014 Oct;167(1):87-99. doi: 10.1111/bjh.13011. Epub 2014 Jul 4. PubMed PMID: 24995804; PubMed Central PMCID: PMC4207443.

9: Marlow H, Matus DQ, Martindale MQ. Ectopic activation of the canonical wnt signaling pathway affects ectodermal patterning along the primary axis during larval development in the anthozoan Nematostella vectensis. Dev Biol. 2013 Aug 15;380(2):324-34. doi: 10.1016/j.ydbio.2013.05.022. Epub 2013 May 27. PubMed PMID: 23722001; PubMed Central PMCID: PMC4792810.