Cercosporamide | CAS# 131436-22-1 | Antineoplastic

MedKoo Cat#: 412578 | Name: Cercosporamide

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Description:

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

Cercosporamide is an antineoplastic, broad-spectrum natural antifungal compound, and selective and highly potent fungal Pkc1 kinase inhibitor.

Chemical Structure

Cercosporamide

CAS#131436-22-1

Theoretical Analysis

MedKoo Cat#: 412578

Name: Cercosporamide

CAS#: 131436-22-1

Chemical Formula: C16H13NO7

Exact Mass: 331.0692

Molecular Weight: 331.28

Elemental Analysis: C, 58.01; H, 3.96; N, 4.23; O, 33.81

Price and Availability

Size	Price	Availability	Quantity
500µg	USD 450.00	2 Weeks

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Synonym

Cercosporamide; (-)-Cercosporamide

IUPAC/Chemical Name

4-Dibenzofurancarboxamide, 8-acetyl-9,9a-dihydro-1,3,7-trihydroxy-9a-methyl-9-oxo-, (S)-

InChi Key

GEWLYFZWVLXQME-MRXNPFEDSA-N

InChi Code

InChI=1S/C16H13NO7/c1-5(18)10-7(20)4-9-16(2,14(10)22)12-8(21)3-6(19)11(15(17)23)13(12)24-9/h3-4,19-21H,1-2H3,(H2,17,23)/t16-/m1/s1

SMILES Code

O=C(C1=C(C([C@@]23C)=C(O)C=C1O)OC2=CC(O)=C(C(C)=O)C3=O)N

Appearance

Solid powder

Purity

>95% (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

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Product Data

Product Data

Instruction

View handling instruction

Biological target:

Cercosporamide is a highly potent, ATP-competitive Pkc1 kinase inhibitor, with an IC50 of <50 nM and a Ki of <7 nM. Cercosporamide is a unique Mnk inhibitor.

In vitro activity:

Cercosporamide, an antifungal agent that is recently shown to act as a unique Mnk inhibitor, exhibits antileukemic properties. Cercosporamide is a potent inhibitor of phosphorylation of eIF4E at Ser209 in AML cells and results in potent inhibitory effects on primitive leukemic progenitors (CFU-L) from AML patients. To determine whether Cercosporamide exhibits negative regulatory effects on cell proliferation and viability of leukemia cells, MTT assays are conducted. When U937 cells are incubated in the presence or absence of the increasing doses of Cercosporamide, a dose-dependent suppression of cell growth is found. Similar experiments with comparable results are seen when the effects of Cercosporamide on MM6 and K562 cells are examined. Reference: Blood. 2013 May 2;121(18):3675-81. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23509154/

In vivo activity:

Treatment with Cercosporamide or Ara-C alone significantly suppresses xenograft growth when compared with the respective vehicle (P<0.011 for 10 mg/kg twice-daily Cercosporamide; P<0.006 for Cercosporamide 20 mg/kg daily; P<0.0374 for Ara-C). The combination of Cercosporamide 10 mg/kg twice daily plus Ara-C is significantly more effective than either agent alone (P<0.0009 vs Cercosporamide; P=0.005 vs Ara-C; P<0.0001 vs either vehicle). Cercosporamide (20 mg/kg once daily) in combination with Ara-C shows similar effects, with significant inhibition of tumor growth vs captisol (P<0.0001) or water (P=0.0003), but does not show statistical significance vs Cercosporamide alone (20 mg/kg) or Ara-C alone. Reference: Blood. 2013 May 2;121(18):3675-81. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23509154/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	3.3	10.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 331.28 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.

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. Altman JK, Szilard A, Konicek BW, Iversen PW, Kroczynska B, Glaser H, Sassano A, Vakana E, Graff JR, Platanias LC. Inhibition of Mnk kinase activity by cercosporamide and suppressive effects on acute myeloid leukemia precursors. Blood. 2013 May 2;121(18):3675-81. doi: 10.1182/blood-2013-01-477216. Epub 2013 Mar 18. PMID: 23509154; PMCID: PMC3643766. 2. Sussman A, Huss K, Chio LC, Heidler S, Shaw M, Ma D, Zhu G, Campbell RM, Park TS, Kulanthaivel P, Scott JE, Carpenter JW, Strege MA, Belvo MD, Swartling JR, Fischl A, Yeh WK, Shih C, Ye XS. Discovery of cercosporamide, a known antifungal natural product, as a selective Pkc1 kinase inhibitor through high-throughput screening. Eukaryot Cell. 2004 Aug;3(4):932-43. doi: 10.1128/EC.3.4.932-943.2004. PMID: 15302826; PMCID: PMC500880.

In vivo protocol:

1: Hoeksma J, van der Zon GCM, Ten Dijke P, den Hertog J. Cercosporamide inhibits bone morphogenetic protein receptor type I kinase activity in zebrafish. Dis Model Mech. 2020 Sep 24;13(9):dmm045971. doi: 10.1242/dmm.045971. PMID: 32820031; PMCID: PMC7522027. 2: Furukawa A, Arita T, Satoh S, Araki K, Kuroha M, Ohsumi J. (-)-Cercosporamide derivatives as novel antihyperglycemic agents. Bioorg Med Chem Lett. 2009 Feb 1;19(3):724-6. doi: 10.1016/j.bmcl.2008.12.035. Epub 2008 Dec 11. PMID: 19109017. 3: Alles SRA, Smith PA. Peripheral Voltage-Gated Cation Channels in Neuropathic Pain and Their Potential as Therapeutic Targets. Front Pain Res (Lausanne). 2021 Dec 13;2:750583. doi: 10.3389/fpain.2021.750583. PMID: 35295464; PMCID: PMC8915663. 4: Dao VH, Ourliac-Garnier I, Logé C, McCarthy FO, Bach S, da Silva TG, Denevault-Sabourin C, Thiéfaine J, Baratte B, Robert T, Gouilleux F, Brachet- Botineau M, Bazin MA, Marchand P. Dibenzofuran Derivatives Inspired from Cercosporamide as Dual Inhibitors of Pim and CLK1 Kinases. Molecules. 2021 Oct 30;26(21):6572. doi: 10.3390/molecules26216572. PMID: 34770981; PMCID: PMC8587151. 5: Chen S, Cui L, Hu Q, Shen Y, Jiang Y, Zhao J. Preclinical evidence that MNK/eIF4E inhibition by cercosporamide enhances the response to antiangiogenic TKI and mTOR inhibitor in renal cell carcinoma. Biochem Biophys Res Commun. 2020 Sep 10;530(1):142-148. doi: 10.1016/j.bbrc.2020.06.133. Epub 2020 Jul 30. PMID: 32828276. 6: Zhu Y, Wang C, Li M, Yang X. Targeting of MNK/eIF4E overcomes chemoresistance in cervical cancer. J Pharm Pharmacol. 2021 Sep 7;73(10):1418-1426. doi: 10.1093/jpp/rgab094. PMID: 34254647. 7: Altman JK, Szilard A, Konicek BW, Iversen PW, Kroczynska B, Glaser H, Sassano A, Vakana E, Graff JR, Platanias LC. Inhibition of Mnk kinase activity by cercosporamide and suppressive effects on acute myeloid leukemia precursors. Blood. 2013 May 2;121(18):3675-81. doi: 10.1182/blood-2013-01-477216. Epub 2013 Mar 18. PMID: 23509154; PMCID: PMC3643766. 8: Liu Y, Sun L, Su X, Guo S. Inhibition of eukaryotic initiation factor 4E phosphorylation by cercosporamide selectively suppresses angiogenesis, growth and survival of human hepatocellular carcinoma. Biomed Pharmacother. 2016 Dec;84:237-243. doi: 10.1016/j.biopha.2016.09.038. Epub 2016 Sep 20. PMID: 27662474. 9: Dao VH, Ourliac-Garnier I, Bazin MA, Jacquot C, Baratte B, Ruchaud S, Bach S, Grovel O, Le Pape P, Marchand P. Benzofuro[3,2-d]pyrimidines inspired from cercosporamide CaPkc1 inhibitor: Synthesis and evaluation of fluconazole susceptibility restoration. Bioorg Med Chem Lett. 2018 Jul 15;28(13):2250-2255. doi: 10.1016/j.bmcl.2018.05.044. Epub 2018 May 23. PMID: 29853332. 10: Furukawa A, Arita T, Fukuzaki T, Mori M, Honda T, Satoh S, Matsui Y, Wakabayashi K, Hayashi S, Nakamura K, Araki K, Kuroha M, Tanaka J, Wakimoto S, Suzuki O, Ohsumi J. Synthesis and biological evaluation of novel (-)-Cercosporamide derivatives as potent selective PPARγ modulators. Eur J Med Chem. 2012 Aug;54:522-33. doi: 10.1016/j.ejmech.2012.05.040. Epub 2012 Jun 7. PMID: 22727448. 11: Sussman A, Huss K, Chio LC, Heidler S, Shaw M, Ma D, Zhu G, Campbell RM, Park TS, Kulanthaivel P, Scott JE, Carpenter JW, Strege MA, Belvo MD, Swartling JR, Fischl A, Yeh WK, Shih C, Ye XS. Discovery of cercosporamide, a known antifungal natural product, as a selective Pkc1 kinase inhibitor through high- throughput screening. Eukaryot Cell. 2004 Aug;3(4):932-43. doi: 10.1128/EC.3.4.932-943.2004. PMID: 15302826; PMCID: PMC500880. 12: Furukawa A, Arita T, Satoh S, Wakabayashi K, Hayashi S, Matsui Y, Araki K, Kuroha M, Ohsumi J. Discovery of a novel selective PPARgamma modulator from (-)-Cercosporamide derivatives. Bioorg Med Chem Lett. 2010 Apr 1;20(7):2095-8. doi: 10.1016/j.bmcl.2010.02.073. Epub 2010 Feb 20. PMID: 20219371. 13: Bazin MA, Bodero L, Tomasoni C, Rousseau B, Roussakis C, Marchand P. Synthesis and antiproliferative activity of benzofuran-based analogs of cercosporamide against non-small cell lung cancer cell lines. Eur J Med Chem. 2013 Nov;69:823-32. doi: 10.1016/j.ejmech.2013.09.013. Epub 2013 Sep 18. PMID: 24121233. 14: Rai M, Zimowska B, Gade A, Ingle P. Phoma spp. an untapped treasure of cytotoxic compounds: current status and perspectives. Appl Microbiol Biotechnol. 2023 Aug;107(16):4991-5001. doi: 10.1007/s00253-023-12635-9. Epub 2023 Jul 4. PMID: 37401998. 15: Wang L, Shen J, Xu L, Gao J, Zhang C, Wang Y, Chen F. A metabolite of endophytic fungus Cadophora orchidicola from Kalimeris indica serves as a potential fungicide and TLR4 agonist. J Appl Microbiol. 2019 May;126(5):1383-1390. doi: 10.1111/jam.14239. Epub 2019 Mar 19. PMID: 30811736. 16: Zhang Q, Li H, Li Q, Hu Q, Liu B. MNK/eIF4E inhibition overcomes anlotinib resistance in non-small cell lung cancer. Fundam Clin Pharmacol. 2023 Apr;37(2):245-252. doi: 10.1111/fcp.12850. Epub 2022 Nov 21. PMID: 36355605. 17: Singh MP, Leighton MM, Barbieri LR, Roll DM, Urbance SE, Hoshan L, McDonald LA. Fermentative production of self-toxic fungal secondary metabolites. J Ind Microbiol Biotechnol. 2010 Apr;37(4):335-40. doi: 10.1007/s10295-009-0678-9. Epub 2009 Dec 24. PMID: 20033470. 18: Furukawa A, Arita T, Fukuzaki T, Satoh S, Mori M, Honda T, Matsui Y, Wakabayashi K, Hayashi S, Araki K, Ohsumi J. Substituents at the naphthalene C3 position of (-)-Cercosporamide derivatives significantly affect the maximal efficacy as PPARγ partial agonists. Bioorg Med Chem Lett. 2012 Feb 1;22(3):1348-51. doi: 10.1016/j.bmcl.2011.12.066. Epub 2011 Dec 16. PMID: 22225641. 19: Moy JK, Khoutorsky A, Asiedu MN, Black BJ, Kuhn JL, Barragán-Iglesias P, Megat S, Burton MD, Burgos-Vega CC, Melemedjian OK, Boitano S, Vagner J, Gkogkas CG, Pancrazio JJ, Mogil JS, Dussor G, Sonenberg N, Price TJ. The MNK-eIF4E Signaling Axis Contributes to Injury-Induced Nociceptive Plasticity and the Development of Chronic Pain. J Neurosci. 2017 Aug 2;37(31):7481-7499. doi: 10.1523/JNEUROSCI.0220-17.2017. Epub 2017 Jul 3. PMID: 28674170; PMCID: PMC5546114. 20: Black BJ, Atmaramani R, Kumaraju R, Plagens S, Romero-Ortega M, Dussor G, Price TJ, Campbell ZT, Pancrazio JJ. Adult mouse sensory neurons on microelectrode arrays exhibit increased spontaneous and stimulus-evoked activity in the presence of interleukin-6. J Neurophysiol. 2018 Sep 1;120(3):1374-1385. doi: 10.1152/jn.00158.2018. Epub 2018 Jun 27. PMID: 29947589; PMCID: PMC6171072.

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