MedKoo Cat#: 581757 | Name: Zotatifin
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Description:

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

Zotatifin, also known as eFT226, is a potent and selective inhibitor of eIF4A, is efficacious in preclinical models of lymphoma. eFT226 promotes eIF4A1 binding to specific 5’-UTR polypurine and/or G-quadraplex recognition motifs leading to a selective block in ribosome mRNA scanning. eFT226 shows potent anti-proliferative activity (GI50 < 15 nM) against a panel of B-cell lymphoma cell lines. Treatment with eFT226 leads to coordinated inhibition of MYC, CCND1/3, BCL2 or MCL1 protein expression resulting in significant anti-tumor activity.

Chemical Structure

Zotatifin
Zotatifin
CAS#2098191-53-6

Theoretical Analysis

MedKoo Cat#: 581757

Name: Zotatifin

CAS#: 2098191-53-6

Chemical Formula: C28H29N3O5

Exact Mass: 487.2107

Molecular Weight: 487.56

Elemental Analysis: C, 68.98; H, 6.00; N, 8.62; O, 16.41

Price and Availability

Size Price Availability Quantity
1mg USD 1,850.00 2 Weeks
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Related CAS #
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Synonym
zotatifin; eFT226; eFT 226; eFT 226;
IUPAC/Chemical Name
4-{(5aR,6S,7S,8R,8aS)-7-[(dimethylamino)methyl]-8,8a-dihydroxy-1,3-dimethoxy-6-phenyl-6,7,8,8a-tetrahydro-5aH-cyclopenta[4,5]furo[3,2-c]pyridin- 5a-yl}benzonitrile
InChi Key
QYCXWOACFWMQFO-WZWZCULESA-N
InChi Code
InChI=1S/C28H29N3O5/c1-31(2)16-20-23(18-8-6-5-7-9-18)28(19-12-10-17(15-29)11-13-19)27(33,25(20)32)24-21(36-28)14-22(34-3)30-26(24)35-4/h5-14,20,23,25,32-33H,16H2,1-4H3/t20-,23-,25-,27+,28+/m1/s1
SMILES Code
N#CC1=CC=C([C@@]2(O3)[C@@](C4=C3C=C(OC)N=C4OC)(O)[C@H](O)[C@H](CN(C)C)[C@H]2C5=CC=CC=C5)C=C1
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
>3 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

Preparing Stock Solutions

The following data is based on the product molecular weight 487.56 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
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PMID: 39078310; PMCID: PMC11443218. 3: Boyer JA, Sharma M, Dorso MA, Mai N, Amor C, Reiter JM, Kannan R, Gadal S, Xu J, Miele M, Li Z, Chen X, Chang Q, Pareja F, Worland S, Warner D, Sperry S, Chiang GG, Thompson PA, Yang G, Ouerfelli O, de Stanchina E, Wendel HG, Rosen EY, Chandarlapaty S, Rosen N. eIF4A controls translation of estrogen receptor alpha and is a therapeutic target in advanced breast cancer. bioRxiv [Preprint]. 2024 May 11:2024.05.08.593195. doi: 10.1101/2024.05.08.593195. PMID: 38766126; PMCID: PMC11100762. 4: Goldstein SI, Fan AC, Wang Z, Naineni SK, Cencic R, Garcia-Gutierrez SB, Patel K, Huang S, Brown LE, Emili A, Porco JA Jr. Discovery of RNA-Protein Molecular Clamps Using Proteome-Wide Stability Assays. bioRxiv [Preprint]. 2024 Dec 21:2024.04.19.590252. doi: 10.1101/2024.04.19.590252. PMID: 38659867; PMCID: PMC11042367. 5: Zhao N, Kabotyanski EB, Saltzman AB, Malovannaya A, Yuan X, Reineke LC, Lieu N, Gao Y, Pedroza DA, Calderon SJ, Smith AJ, Hamor C, Safari K, Savage S, Zhang B, Zhou J, Solis LM, Hilsenbeck SG, Fan C, Perou CM, Rosen JM. Targeting eIF4A triggers an interferon response to synergize with chemotherapy and suppress triple-negative breast cancer. J Clin Invest. 2023 Dec 15;133(24):e172503. doi: 10.1172/JCI172503. PMID: 37874652; PMCID: PMC10721161. 6: Zhao N, Kabotyanski EB, Saltzman AB, Malovannaya A, Yuan X, Reineke LC, Lieu N, Gao Y, Pedroza DA, Calderon SJ, Smith AJ, Hamor C, Safari K, Savage S, Zhang B, Zhou J, Solis LM, Hilsenbeck SG, Fan C, Perou CM, Rosen JM. Targeting EIF4A triggers an interferon response to synergize with chemotherapy and suppress triple-negative breast cancer. bioRxiv [Preprint]. 2023 Sep 28:2023.09.28.559973. doi: 10.1101/2023.09.28.559973. Update in: J Clin Invest. 2023 Dec 15;133(24):e172503. doi: 10.1172/JCI172503. PMID: 37808840; PMCID: PMC10557675. 7: Schiffmann S, Henke M, Seifert M, Ulshöfer T, Roser LA, Magari F, Wendel HG, Grünweller A, Parnham MJ. Comparing the Effects of Rocaglates on Energy Metabolism and Immune Modulation on Cells of the Human Immune System. Int J Mol Sci. 2023 Mar 20;24(6):5872. doi: 10.3390/ijms24065872. PMID: 36982945; PMCID: PMC10051175. 8: Chan GKL, Maisel S, Hwang YC, Pascual BC, Wolber RRB, Vu P, Patra KC, Bouhaddou M, Kenerson HL, Lim HC, Long D, Yeung RS, Sethupathy P, Swaney DL, Krogan NJ, Turnham RE, Riehle KJ, Scott JD, Bardeesy N, Gordan JD. Oncogenic PKA signaling increases c-MYC protein expression through multiple targetable mechanisms. Elife. 2023 Jan 24;12:e69521. doi: 10.7554/eLife.69521. PMID: 36692000; PMCID: PMC9925115. 9: Fava VM, Bourgey M, Nawarathna PM, Orlova M, Cassart P, Vinh DC, Cheng MP, Bourque G, Schurr E, Langlais D. A systems biology approach identifies candidate drugs to reduce mortality in severely ill patients with COVID-19. Sci Adv. 2022 Jun 3;8(22):eabm2510. doi: 10.1126/sciadv.abm2510. Epub 2022 Jun 1. PMID: 35648852; PMCID: PMC9159580. 10: Pramanik D, Pawar AB, Roy S, Singh JK. Mechanistic insights of key host proteins and potential repurposed inhibitors regulating SARS-CoV-2 pathway. J Comput Chem. 2022 Jul 5;43(18):1237-1250. doi: 10.1002/jcc.26888. Epub 2022 May 10. PMID: 35535951; PMCID: PMC9348233. 11: Obermann W, Friedrich A, Madhugiri R, Klemm P, Mengel JP, Hain T, Pleschka S, Wendel HG, Hartmann RK, Schiffmann S, Ziebuhr J, Müller C, Grünweller A. Rocaglates as Antivirals: Comparing the Effects on Viral Resistance, Anti- Coronaviral Activity, RNA-Clamping on eIF4A and Immune Cell Toxicity. Viruses. 2022 Mar 3;14(3):519. doi: 10.3390/v14030519. PMID: 35336926; PMCID: PMC8950828. 12: Gerson-Gurwitz A, Young NP, Goel VK, Eam B, Stumpf CR, Chen J, Fish S, Barrera M, Sung E, Staunton J, Chiang GG, Webster KR, Thompson PA. Zotatifin, an eIF4A-Selective Inhibitor, Blocks Tumor Growth in Receptor Tyrosine Kinase Driven Tumors. Front Oncol. 2021 Nov 24;11:766298. doi: 10.3389/fonc.2021.766298. PMID: 34900714; PMCID: PMC8663026. 13: Ho JJD, Cunningham TA, Manara P, Coughlin CA, Arumov A, Roberts ER, Osteen A, Kumar P, Bilbao D, Krieger JR, Lee S, Schatz JH. Proteomics reveal cap- dependent translation inhibitors remodel the translation machinery and translatome. Cell Rep. 2021 Oct 12;37(2):109806. doi: 10.1016/j.celrep.2021.109806. PMID: 34644561; PMCID: PMC8558842. 14: Vallianou NG, Tsilingiris D, Christodoulatos GS, Karampela I, Dalamaga M. Anti-viral treatment for SARS-CoV-2 infection: A race against time amidst the ongoing pandemic. Metabol Open. 2021 Jun;10:100096. doi: 10.1016/j.metop.2021.100096. Epub 2021 May 25. PMID: 34056571; PMCID: PMC8143911. 15: Taroncher-Oldenburg G, Müller C, Obermann W, Ziebuhr J, Hartmann RK, Grünweller A. Targeting the DEAD-Box RNA Helicase eIF4A with Rocaglates-A Pan- Antiviral Strategy for Minimizing the Impact of Future RNA Virus Pandemics. Microorganisms. 2021 Mar 5;9(3):540. doi: 10.3390/microorganisms9030540. PMID: 33807988; PMCID: PMC8001013. 16: Sauvat A, Ciccosanti F, Colavita F, Di Rienzo M, Castilletti C, Capobianchi MR, Kepp O, Zitvogel L, Fimia GM, Piacentini M, Kroemer G. On-target versus off- target effects of drugs inhibiting the replication of SARS-CoV-2. Cell Death Dis. 2020 Aug 19;11(8):656. doi: 10.1038/s41419-020-02842-x. PMID: 32814759; PMCID: PMC7434849. 17: Bouhaddou M, Memon D, Meyer B, White KM, Rezelj VV, Correa Marrero M, Polacco BJ, Melnyk JE, Ulferts S, Kaake RM, Batra J, Richards AL, Stevenson E, Gordon DE, Rojc A, Obernier K, Fabius JM, Soucheray M, Miorin L, Moreno E, Koh C, Tran QD, Hardy A, Robinot R, Vallet T, Nilsson-Payant BE, Hernandez-Armenta C, Dunham A, Weigang S, Knerr J, Modak M, Quintero D, Zhou Y, Dugourd A, Valdeolivas A, Patil T, Li Q, Hüttenhain R, Cakir M, Muralidharan M, Kim M, Jang G, Tutuncuoglu B, Hiatt J, Guo JZ, Xu J, Bouhaddou S, Mathy CJP, Gaulton A, Manners EJ, Félix E, Shi Y, Goff M, Lim JK, McBride T, O'Neal MC, Cai Y, Chang JCJ, Broadhurst DJ, Klippsten S, De Wit E, Leach AR, Kortemme T, Shoichet B, Ott M, Saez-Rodriguez J, tenOever BR, Mullins RD, Fischer ER, Kochs G, Grosse R, García-Sastre A, Vignuzzi M, Johnson JR, Shokat KM, Swaney DL, Beltrao P, Krogan NJ. The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell. 2020 Aug 6;182(3):685-712.e19. doi: 10.1016/j.cell.2020.06.034. Epub 2020 Jun 28. PMID: 32645325; PMCID: PMC7321036. 18: Ernst JT, Thompson PA, Nilewski C, Sprengeler PA, Sperry S, Packard G, Michels T, Xiang A, Tran C, Wegerski CJ, Eam B, Young NP, Fish S, Chen J, Howard H, Staunton J, Molter J, Clarine J, Nevarez A, Chiang GG, Appleman JR, Webster KR, Reich SH. Design of Development Candidate eFT226, a First in Class Inhibitor of Eukaryotic Initiation Factor 4A RNA Helicase. J Med Chem. 2020 Jun 11;63(11):5879-5955. doi: 10.1021/acs.jmedchem.0c00182. Epub 2020 May 29. PMID: 32470302.