Galiellalactone | CAS#133613-71-5 | STAT3 inhibitor

MedKoo Cat#: 561877 | Name: Galiellalactone

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Description:

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

Galiellalactone is a natural STAT3 inhibitor. It has been shown to inhibit IL-6-dependent JAK/STAT signaling and induce cell-cycle arrest in G2/M phase and apoptosis in androgen-insensitive prostate cancer cells via activation of ATM/ATR pathway.

Chemical Structure

Galiellalactone

CAS#133613-71-5

Theoretical Analysis

MedKoo Cat#: 561877

Name: Galiellalactone

CAS#: 133613-71-5

Chemical Formula: C11H14O3

Exact Mass: 194.0943

Molecular Weight: 194.23

Elemental Analysis: C, 68.02; H, 7.27; O, 24.71

Price and Availability

Size	Price	Availability	Quantity
1mg	USD 650.00	2 Weeks
5mg	USD 1,750.00	2 Weeks

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Related CAS #

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Synonym

Galiellalactone;

IUPAC/Chemical Name

(4S,5aR,7aR,7bS)-5,5a,6,7,7a,7b-Hexahydro-7b-hydroxy-4-methylindeno[1,7-bc]furan-2(4H)-one

InChi Key

SOIISBQQYAGDKM-QJSROADHSA-N

InChi Code

InChI=1S/C11H14O3/c1-6-4-7-2-3-9-11(7,13)8(5-6)10(12)14-9/h5-7,9,13H,2-4H2,1H3/t6-,7+,9+,11-/m0/s1

SMILES Code

O=C1C2=C[C@@H](C)C[C@@]3([H])CC[C@@]([C@@]23O)([H])O1

Appearance

A lyophilized 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

>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

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Galiellalactone is a selective inhibitor of STAT3 signaling, with an IC50 of 250-500 nM.

In vitro activity:

Galiellalactone significantly reduced the levels of secreted IL8 from DU145 and LNCaP‐IL6 cells and decreased the IL8 mRNA levels in DU145 cells (Figure 3C). Reference: Prostate. 2019 Oct 1; 79(14): 1611–1621. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771992/

In vivo activity:

Consistent with our in vitro data (Fig. 2A), treatment with GPA500 reduced tumor growth compared to control (Fig. 4A). Consequently, the serum PSA in the treated mice was also lower (Fig. 4B). Reference: Sci Rep. 2018; 8: 17307. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251893/

	Solvent	mg/mL	mM
Solubility
	DMSO	1.0	4.99
	Ethanol	1.0	4.99

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 194.23 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:

1. Hellsten R, Lilljebjörn L, Johansson M, Leandersson K, Bjartell A. The STAT3 inhibitor galiellalactone inhibits the generation of MDSC-like monocytes by prostate cancer cells and decreases immunosuppressive and tumorigenic factors. Prostate. 2019 Oct;79(14):1611-1621. doi: 10.1002/pros.23885. Epub 2019 Jul 26. PMID: 31348843; PMCID: PMC6771992. 2. Handle F, Puhr M, Schaefer G, Lorito N, Hoefer J, Gruber M, Guggenberger F, Santer FR, Marques RB, van Weerden WM, Claessens F, Erb HHH, Culig Z. The STAT3 Inhibitor Galiellalactone Reduces IL6-Mediated AR Activity in Benign and Malignant Prostate Models. Mol Cancer Ther. 2018 Dec;17(12):2722-2731. doi: 10.1158/1535-7163.MCT-18-0508. Epub 2018 Sep 25. PMID: 30254184. 3. Canesin G, Maggio V, Palominos M, Stiehm A, Contreras HR, Castellón EA, Morote J, Paciucci R, Maitland NJ, Bjartell A, Hellsten R. STAT3 inhibition with galiellalactone effectively targets the prostate cancer stem-like cell population. Sci Rep. 2020 Aug 18;10(1):13958. doi: 10.1038/s41598-020-70948-5. PMID: 32811873; PMCID: PMC7434889. 4. Thaper D, Vahid S, Kaur R, Kumar S, Nouruzi S, Bishop JL, Johansson M, Zoubeidi A. Galiellalactone inhibits the STAT3/AR signaling axis and suppresses Enzalutamide-resistant Prostate Cancer. Sci Rep. 2018 Nov 23;8(1):17307. doi: 10.1038/s41598-018-35612-z. PMID: 30470788; PMCID: PMC6251893.

In vitro protocol:

In vivo protocol:

1. Canesin G, Maggio V, Palominos M, Stiehm A, Contreras HR, Castellón EA, Morote J, Paciucci R, Maitland NJ, Bjartell A, Hellsten R. STAT3 inhibition with galiellalactone effectively targets the prostate cancer stem-like cell population. Sci Rep. 2020 Aug 18;10(1):13958. doi: 10.1038/s41598-020-70948-5. PMID: 32811873; PMCID: PMC7434889. 2. Thaper D, Vahid S, Kaur R, Kumar S, Nouruzi S, Bishop JL, Johansson M, Zoubeidi A. Galiellalactone inhibits the STAT3/AR signaling axis and suppresses Enzalutamide-resistant Prostate Cancer. Sci Rep. 2018 Nov 23;8(1):17307. doi: 10.1038/s41598-018-35612-z. PMID: 30470788; PMCID: PMC6251893.

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J Med Chem. 2016 May 26;59(10):4551-62. doi: 10.1021/acs.jmedchem.5b01814. Epub 2016 May 3. PubMed PMID: 27111731. 4: García V, Lara-Chica M, Cantarero I, Sterner O, Calzado MA, Muñoz E. Galiellalactone induces cell cycle arrest and apoptosis through the ATM/ATR pathway in prostate cancer cells. Oncotarget. 2016 Jan 26;7(4):4490-506. doi: 10.18632/oncotarget.6606. PubMed PMID: 26683224; PubMed Central PMCID: PMC4826221. 5: Kim T, Han YT, An H, Kim K, Lee J, Suh YG. Diastereoselective Total Synthesis of (-)-Galiellalactone. J Org Chem. 2015 Dec 18;80(24):12193-200. doi: 10.1021/acs.joc.5b02121. Epub 2015 Nov 13. PubMed PMID: 26544529. 6: Canesin G, Evans-Axelsson S, Hellsten R, Sterner O, Krzyzanowska A, Andersson T, Bjartell A. The STAT3 Inhibitor Galiellalactone Effectively Reduces Tumor Growth and Metastatic Spread in an Orthotopic Xenograft Mouse Model of Prostate Cancer. Eur Urol. 2016 Mar;69(3):400-4. doi: 10.1016/j.eururo.2015.06.016. Epub 2015 Jul 2. PubMed PMID: 26144873. 7: Bollmann F, Jäckel S, Schmidtke L, Schrick K, Reinhardt C, Jurk K, Wu Z, Xia N, Li H, Erkel G, Walter U, Kleinert H, Pautz A. Anti-Inflammatory and Anti-Thrombotic Effects of the Fungal Metabolite Galiellalactone in Apolipoprotein E-Deficient Mice. PLoS One. 2015 Jun 15;10(6):e0130401. doi: 10.1371/journal.pone.0130401. eCollection 2015. PubMed PMID: 26076475; PubMed Central PMCID: PMC4468253. 8: Tian JF, Yu RJ, Li XX, Gao H, Guo LD, Li Y, Li J, Tang JS, Yao XS. Galiellalactone analogs and their possible precursors from Sarcosomataceae. Fitoterapia. 2015 Mar;101:92-8. doi: 10.1016/j.fitote.2015.01.002. Epub 2015 Jan 12. PubMed PMID: 25592721. 9: Don-Doncow N, Escobar Z, Johansson M, Kjellström S, Garcia V, Munoz E, Sterner O, Bjartell A, Hellsten R. Galiellalactone is a direct inhibitor of the transcription factor STAT3 in prostate cancer cells. J Biol Chem. 2014 Jun 6;289(23):15969-78. doi: 10.1074/jbc.M114.564252. Epub 2014 Apr 22. PubMed PMID: 24755219; PubMed Central PMCID: PMC4047371. 10: Pérez M, Soler-Torronteras R, Collado JA, Limones CG, Hellsten R, Johansson M, Sterner O, Bjartell A, Calzado MA, Muñoz E. The fungal metabolite galiellalactone interferes with the nuclear import of NF-κB and inhibits HIV-1 replication. Chem Biol Interact. 2014 May 5;214:69-76. doi: 10.1016/j.cbi.2014.02.012. Epub 2014 Mar 11. PubMed PMID: 24631022. 11: Rudolph K, Serwe A, Erkel G. Inhibition of TGF-β signaling by the fungal lactones (S)-curvularin, dehydrocurvularin, oxacyclododecindione and galiellalactone. Cytokine. 2013 Jan;61(1):285-96. doi: 10.1016/j.cyto.2012.10.011. Epub 2012 Nov 5. PubMed PMID: 23134667. 12: Hellsten R, Johansson M, Dahlman A, Sterner O, Bjartell A. Galiellalactone inhibits stem cell-like ALDH-positive prostate cancer cells. PLoS One. 2011;6(7):e22118. doi: 10.1371/journal.pone.0022118. Epub 2011 Jul 11. PubMed PMID: 21779382; PubMed Central PMCID: PMC3133629. 13: Hausding M, Tepe M, Ubel C, Lehr HA, Röhrig B, Höhn Y, Pautz A, Eigenbrod T, Anke T, Kleinert H, Erkel G, Finotto S. Induction of tolerogenic lung CD4+ T cells by local treatment with a pSTAT-3 and pSTAT-5 inhibitor ameliorated experimental allergic asthma. Int Immunol. 2011 Jan;23(1):1-15. doi: 10.1093/intimm/dxq451. Epub 2010 Dec 6. PubMed PMID: 21135031. 14: Gidlöf R, Johansson M, Sterner O. Tandem Pd-catalyzed carbonylation and intramolecular vinyl allene Diels-Alder reaction toward galiellalactone analogues. Org Lett. 2010 Nov 19;12(22):5100-3. doi: 10.1021/ol101989m. Epub 2010 Oct 27. PubMed PMID: 20979411. 15: Hellsten R, Johansson M, Dahlman A, Dizeyi N, Sterner O, Bjartell A. Galiellalactone is a novel therapeutic candidate against hormone-refractory prostate cancer expressing activated Stat3. Prostate. 2008 Feb 15;68(3):269-80. doi: 10.1002/pros.20699. PubMed PMID: 18163422. 16: Lebel H, Parmentier M. Copper-catalyzed methylenation reaction: total synthesis of (+)-desoxygaliellalactone. Org Lett. 2007 Aug 30;9(18):3563-6. Epub 2007 Aug 1. PubMed PMID: 17665920. 17: Johansson M, Sterner O. Synthesis of (-)-galiellalactone. J Antibiot (Tokyo). 2002 Jul;55(7):663-5. PubMed PMID: 12243458. 18: Köpcke B, Weber RW, Anke H. Galiellalactone and its biogenetic precursors as chemotaxonomic markers of the Sarcosomataceae (Ascomycota). Phytochemistry. 2002 Aug;60(7):709-14. PubMed PMID: 12127588. 19: Johansson M, Köpcke B, Anke H, Sterner O. Cyclization of (-)-pregaliellalactone in the fungus Galiella rufa. Angew Chem Int Ed Engl. 2002 Jun 17;41(12):2158-60. PubMed PMID: 19746629. 20: Köpcke B, Johansson M, Sterner O, Anke H. Biologically active secondary metabolites from the ascomycete A111-95. 1. Production, isolation and biological activities. J Antibiot (Tokyo). 2002 Jan;55(1):36-40. PubMed PMID: 11918063.