PRI-724

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

MedKoo CAT#: 205865

CAS#: 1422253-38-0 (PRI-724)

Description: PRI-724, also known as C-82 prodrug/ICG-001 analog, is a potent, specific inhibitor of the canonical Wnt signaling pathway in cancer stem cells with potential antineoplastic activity. Wnt signaling pathway inhibitor PRI-724 specifically inhibits the recruiting of beta-catenin with its coactivator CBP (the binding protein of the cAMP response element-binding protein CREB); together with other transcription factors beta-catenin/CBP binds to WRE (Wnt-responsive element) and activates transcription of a wide range of target genes of Wnt/beta-catenin signaling. Note: Chemical structures of ICG-001 and PRR-724 look very close, but they are not the same molecule. Many vendors confused them.


Price and Availability

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PRI-724 is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 205865
Name: PRI-724
CAS#: 1422253-38-0 (PRI-724)
Chemical Formula: C33H32N4O4
Exact Mass: 548.24236
Molecular Weight: 548.63
Elemental Analysis: C, 72.24; H, 5.88; N, 10.21; O, 11.66


Related CAS #: 1422253-38-0 (PRI-724)   847591-62-2 (deleted)   780757-88-2 (ICG001)  

Synonym: PRI724; PRI-724; PRI 724; C-82 prodrug; ICG-001 analog; ICG001 analog; ICG 001 analog;

IUPAC/Chemical Name: (6S,9aS)-N-benzyl-6-(4-hydroxybenzyl)-8-(naphthalen-1-ylmethyl)-4,7-dioxooctahydro-1H-pyrazino[1,2-a]pyrimidine-1-carboxamide

InChi Key: HQWTUOLCGKIECB-XZWHSSHBSA-N

InChi Code: InChI=1S/C33H32N4O4/c38-27-15-13-23(14-16-27)19-29-32(40)35(21-26-11-6-10-25-9-4-5-12-28(25)26)22-30-36(18-17-31(39)37(29)30)33(41)34-20-24-7-2-1-3-8-24/h1-16,29-30,38H,17-22H2,(H,34,41)/t29-,30+/m0/s1

SMILES Code: O=C(N(CC1)[C@](CN(CC2=C3C=CC=CC3=CC=C2)C([C@@H]4CC5=CC=C(O)C=C5)=O)([H])N4C1=O)NCC6=CC=CC=C6


Technical Data

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, 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).

Harmonized System Code:
2934.99.90.01


Additional Information

Structure of PRI-724 was from below paper:
1: Osawa Y, Kojika E, Nishikawa K, Kimura M, Osakaya S, Miyauchi H, Kanto T, Kawakami Y, Kimura K. Programmed cell death ligand 1 (PD-L1) blockade attenuates metastatic colon cancer growth in cAMP-response element-binding protein (CREB)-binding protein (CBP)/β-catenin inhibitor-treated livers. Oncotarget. 2019 Apr 30;10(32):3013-3026. doi: 10.18632/oncotarget.26892. eCollection 2019 Apr 30. PubMed PMID: 31105882; PubMed Central PMCID: PMC6508964.


References

1: Okazaki H, Sato S, Koyama K, Morizumi S, Abe S, Azuma M, Chen Y, Goto H, Aono Y, Ogawa H, Kagawa K, Nishimura H, Kawano H, Toyoda Y, Uehara H, Kouji H, Nishioka Y. The novel inhibitor PRI-724 for Wnt/β-catenin/CBP signaling ameliorates bleomycin-induced pulmonary fibrosis in mice. Exp Lung Res. 2019 Jul 12:1-12. doi: 10.1080/01902148.2019.1638466. [Epub ahead of print] PubMed PMID: 31298961.

2: Rao P, Pang M, Qiao X, Yu H, Wang H, Yang Y, Ren X, Hu M, Chen T, Cao Q, Wang Y, Khushi M, Zhang G, Wang YM, Heok P'ng C, Nankivell B, Lee VW, Alexander SI, Zheng G, Harris DC. Promotion of β-catenin/Foxo1 signaling ameliorates renal interstitial fibrosis. Lab Invest. 2019 Jun 26. doi: 10.1038/s41374-019-0276-z. [Epub ahead of print] PubMed PMID: 31243340.

3: Osawa Y, Kojika E, Nishikawa K, Kimura M, Osakaya S, Miyauchi H, Kanto T, Kawakami Y, Kimura K. Programmed cell death ligand 1 (PD-L1) blockade attenuates metastatic colon cancer growth in cAMP-response element-binding protein (CREB)-binding protein (CBP)/β-catenin inhibitor-treated livers. Oncotarget. 2019 Apr 30;10(32):3013-3026. doi: 10.18632/oncotarget.26892. eCollection 2019 Apr 30. PubMed PMID: 31105882; PubMed Central PMCID: PMC6508964.

4: Kleszcz R, Szymańska A, Krajka-Kuźniak V, Baer-Dubowska W, Paluszczak J. Inhibition of CBP/β-catenin and porcupine attenuates Wnt signaling and induces apoptosis in head and neck carcinoma cells. Cell Oncol (Dordr). 2019 Aug;42(4):505-520. doi: 10.1007/s13402-019-00440-4. Epub 2019 May 14. PubMed PMID: 31089983.

5: Bocchicchio S, Tesone M, Irusta G. Convergence of Wnt and Notch signaling controls ovarian cancer cell survival. J Cell Physiol. 2019 May 13. doi: 10.1002/jcp.28775. [Epub ahead of print] PubMed PMID: 31087357.

6: Taiyab A, Holms J, West-Mays JA. β-Catenin/Smad3 Interaction Regulates Transforming Growth Factor-β-Induced Epithelial to Mesenchymal Transition in the Lens. Int J Mol Sci. 2019 Apr 27;20(9). pii: E2078. doi: 10.3390/ijms20092078. PubMed PMID: 31035577; PubMed Central PMCID: PMC6540099.

7: Cui Y, Wu X, Lin C, Zhang X, Ye L, Ren L, Chen M, Yang M, Li Y, Li M, Li J, Guan J, Song L. AKIP1 promotes early recurrence of hepatocellular carcinoma through activating the Wnt/β-catenin/CBP signaling pathway. Oncogene. 2019 Jul;38(27):5516-5529. doi: 10.1038/s41388-019-0807-5. Epub 2019 Apr 1. PubMed PMID: 30936461.

8: Chen Y, Wen H, Zhou C, Su Q, Lin Y, Xie Y, Huang Y, Qiu Q, Lin J, Huang X, Tan W, Min C, Wang C. TNF-α derived from M2 tumor-associated macrophages promotes epithelial-mesenchymal transition and cancer stemness through the Wnt/β-catenin pathway in SMMC-7721 hepatocellular carcinoma cells. Exp Cell Res. 2019 May 1;378(1):41-50. doi: 10.1016/j.yexcr.2019.03.005. Epub 2019 Mar 4. PubMed PMID: 30844387.

9: Mazzu YZ, Hu Y, Shen Y, Tuschl T, Singer S. miR-193b regulates tumorigenesis in liposarcoma cells via PDGFR, TGFβ, and Wnt signaling. Sci Rep. 2019 Mar 1;9(1):3197. doi: 10.1038/s41598-019-39560-0. PubMed PMID: 30824765; PubMed Central PMCID: PMC6397171.

10: Sun HY, Wang XL, Ma LC, Yang M, Yang HJ, Huang HW, Zhao GA. Influence of MiR-154 on myocardial apoptosis in rats with acute myocardial infarction through Wnt/β-catenin signaling pathway. Eur Rev Med Pharmacol Sci. 2019 Jan;23(2):818-825. doi: 10.26355/eurrev_201901_16896. PubMed PMID: 30720190.

11: Xiao L, Xu B, Zhou L, Tan RJ, Zhou D, Fu H, Li A, Hou FF, Liu Y. Wnt/β-catenin regulates blood pressure and kidney injury in rats. Biochim Biophys Acta Mol Basis Dis. 2019 Jun 1;1865(6):1313-1322. doi: 10.1016/j.bbadis.2019.01.027. Epub 2019 Jan 30. PubMed PMID: 30710617; PubMed Central PMCID: PMC6502648.

12: Zhang QW, Zhang XT, Tang CT, Lin XL, Ge ZZ, Li XB. EGFL6 promotes cell proliferation in colorectal cancer via regulation of the WNT/β-catenin pathway. Mol Carcinog. 2019 Jun;58(6):967-979. doi: 10.1002/mc.22985. Epub 2019 Mar 3. PubMed PMID: 30693973.

13: Fang F, VanCleave A, Helmuth R, Torres H, Rickel K, Wollenzien H, Sun H, Zeng E, Zhao J, Tao J. Targeting the Wnt/β-catenin pathway in human osteosarcoma cells. Oncotarget. 2018 Dec 4;9(95):36780-36792. doi: 10.18632/oncotarget.26377. eCollection 2018 Dec 4. PubMed PMID: 30613366; PubMed Central PMCID: PMC6298399.

14: Yang Y, Feng X, Liu X, Wang Y, Hu M, Cao Q, Zhang Z, Zhao L, Zhang J, Guo R, Wang H, Qiao X, Wang L, Zheng G. Fate alteration of bone marrow-derived macrophages ameliorates kidney fibrosis in murine model of unilateral ureteral obstruction. Nephrol Dial Transplant. 2018 Dec 24. doi: 10.1093/ndt/gfy381. [Epub ahead of print] PubMed PMID: 30590718.

15: Huang Z, Yang M, Li Y, Yang F, Feng Y. Exosomes Derived from Hypoxic Colorectal Cancer Cells Transfer Wnt4 to Normoxic Cells to Elicit a Prometastatic Phenotype. Int J Biol Sci. 2018 Nov 13;14(14):2094-2102. doi: 10.7150/ijbs.28288. eCollection 2018. PubMed PMID: 30585272; PubMed Central PMCID: PMC6299371.

16: Ring A, Nguyen C, Smbatyan G, Tripathy D, Yu M, Press M, Kahn M, Lang JE. CBP/β-Catenin/FOXM1 Is a Novel Therapeutic Target in Triple Negative Breast Cancer. Cancers (Basel). 2018 Dec 19;10(12). pii: E525. doi: 10.3390/cancers10120525. PubMed PMID: 30572639; PubMed Central PMCID: PMC6315782.

17: Chan LS, Man OY, Kwok HH, Chen L, Chan KC, Lung HL, Ngan RK, Wong RN, Lo KW, Lee AW, Tsao GS, Kahn M, Lung ML, Mak NK. The Wnt modulator ICG 001 mediates the inhibition of nasopharyngeal carcinoma cell migration in vitro via the miR 150/CD44 axis. Int J Oncol. 2019 Mar;54(3):1010-1020. doi: 10.3892/ijo.2018.4664. Epub 2018 Dec 12. PubMed PMID: 30569106.

18: Itaba N, Noda I, Oka H, Kono Y, Okinaka K, Yokobata T, Okazaki S, Morimoto M, Shiota G. Hepatic cell sheets engineered from human mesenchymal stem cells with a single small molecule compound IC-2 ameliorate acute liver injury in mice. Regen Ther. 2018 Aug 24;9:45-57. doi: 10.1016/j.reth.2018.07.001. eCollection 2018 Dec. PubMed PMID: 30525075; PubMed Central PMCID: PMC6222293.

19: Li KL, Zhang L, Yang XM, Fang Q, Yin XF, Wei HM, Zhou T, Li YB, Chen XL, Tang F, Li YH, Chang JF, Li W, Sun F. Histone acetyltransferase CBP-related H3K23 acetylation contributes to courtship learning in Drosophila. BMC Dev Biol. 2018 Nov 20;18(1):20. doi: 10.1186/s12861-018-0179-z. PubMed PMID: 30458702; PubMed Central PMCID: PMC6247617.

20: Nishikawa K, Osawa Y, Kimura K. Wnt/β-Catenin Signaling as a Potential Target for the Treatment of Liver Cirrhosis Using Antifibrotic Drugs. Int J Mol Sci. 2018 Oct 10;19(10). pii: E3103. doi: 10.3390/ijms19103103. Review. PubMed PMID: 30308992; PubMed Central PMCID: PMC6213128.