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Guadecitabine (SGI-110): an investigational drug for the treatment of myelodysplastic syndrome and acute myeloid leukemia.
Daher-Reyes GS, Merchan BM, Yee KWL. Daher-Reyes GS, et al. Expert Opin Investig Drugs. 2019 Oct;28(10):835-849. doi: 10.1080/13543784.2019.1667331. Epub 2019 Sep 19. Expert Opin Investig Drugs. 2019. PMID: 31510809 Review.
Areas covered: This article reviews the mechanism of action, pharmacology, safety profile and clinical efficacy of subcutaneous guadecitabine, a second-generation DNA methylation inhibitor in development for the treatment of AML and MDS. Expert opinion: Although guadeci
Areas covered: This article reviews the mechanism of action, pharmacology, safety profile and clinical efficacy of subcutaneous guadecita
Guadecitabine (SGI-110) in patients with intermediate or high-risk myelodysplastic syndromes: phase 2 results from a multicentre, open-label, randomised, phase 1/2 trial.
Garcia-Manero G, Roboz G, Walsh K, Kantarjian H, Ritchie E, Kropf P, O'Connell C, Tibes R, Lunin S, Rosenblat T, Yee K, Stock W, Griffiths E, Mace J, Podoltsev N, Berdeja J, Jabbour E, Issa JJ, Hao Y, Keer HN, Azab M, Savona MR. Garcia-Manero G, et al. Lancet Haematol. 2019 Jun;6(6):e317-e327. doi: 10.1016/S2352-3026(19)30029-8. Epub 2019 May 3. Lancet Haematol. 2019. PMID: 31060979 Clinical Trial.
BACKGROUND: Guadecitabine is a next-generation hypomethylating agent whose active metabolite decitabine has a longer in-vivo exposure time than intravenous decitabine. ...Patients were randomly assigned (1:1) using a computer algorithm for dynamic randomisation to subcutan …
BACKGROUND: Guadecitabine is a next-generation hypomethylating agent whose active metabolite decitabine has a longer in-vivo exposure …
Next-generation hypomethylating agent SGI-110 primes acute myeloid leukemia cells to IAP antagonist by activating extrinsic and intrinsic apoptosis pathways.
Dittmann J, Haydn T, Metzger P, Ward GA, Boerries M, Vogler M, Fulda S. Dittmann J, et al. Cell Death Differ. 2020 Jun;27(6):1878-1895. doi: 10.1038/s41418-019-0465-8. Epub 2019 Dec 12. Cell Death Differ. 2020. PMID: 31831875
Also, TNFalpha-blocking antibody Enbrel had little protective effect on SGI-110/ASTX660-induced cell death. Further, SGI-110 and ASTX660 acted in concert to promote cleavage of caspase-8 and BID, thereby providing a link between extrinsic and intrinsic …
Also, TNFalpha-blocking antibody Enbrel had little protective effect on SGI-110/ASTX660-induced cell death. Further, SGI
Guadecitabine (SGI-110) priming sensitizes hepatocellular carcinoma cells to oxaliplatin.
Kuang Y, El-Khoueiry A, Taverna P, Ljungman M, Neamati N. Kuang Y, et al. Mol Oncol. 2015 Nov;9(9):1799-814. doi: 10.1016/j.molonc.2015.06.002. Epub 2015 Jun 16. Mol Oncol. 2015. PMID: 26160429 Free PMC article.
Bromouridine-labeled RNA sequencing (Bru-seq) was employed to elucidate the effects of SGI-110 and/or oxaliplatin on genome-wide transcription. SGI-110 and the combination treatment inhibited the expression of genes involved in WNT/EGF/IGF signaling. . …
Bromouridine-labeled RNA sequencing (Bru-seq) was employed to elucidate the effects of SGI-110 and/or oxaliplatin on genome-wi …
Integrative Epigenetic Analysis Reveals Therapeutic Targets to the DNA Methyltransferase Inhibitor Guadecitabine (SGI-110) in Hepatocellular Carcinoma.
Liu M, Zhang L, Li H, Hinoue T, Zhou W, Ohtani H, El-Khoueiry A, Daniels J, O'Connell C, Dorff TB, Lu Q, Weisenberger DJ, Liang G. Liu M, et al. Hepatology. 2018 Oct;68(4):1412-1428. doi: 10.1002/hep.30091. Hepatology. 2018. PMID: 29774579 Free PMC article.
Each HCC cell line represents a different DNA methylation subtype of primary HCC tumors based on TCGA data. After SGI-110 treatment, all cell lines were sensitive to SGI-110 with prolonged antiproliferation effects. ...Finally, about 48% of frequently …
Each HCC cell line represents a different DNA methylation subtype of primary HCC tumors based on TCGA data. After SGI-110 trea …
SGI-110 and entinostat therapy reduces lung tumor burden and reprograms the epigenome.
Tellez CS, Grimes MJ, Picchi MA, Liu Y, March TH, Reed MD, Oganesian A, Taverna P, Belinsky SA. Tellez CS, et al. Int J Cancer. 2014 Nov 1;135(9):2223-31. doi: 10.1002/ijc.28865. Epub 2014 Apr 5. Int J Cancer. 2014. PMID: 24668305 Free article.
SGI-110 caused widespread demethylation of more than 300 gene promoters and microarray analysis revealed expression changes for 212 and 592 genes with SGI-110 alone or in combination with entinostat. ...These preclinical in vivo findings demonstrate th
SGI-110 caused widespread demethylation of more than 300 gene promoters and microarray analysis revealed expression changes fo
SPIRE - combining SGI-110 with cisplatin and gemcitabine chemotherapy for solid malignancies including bladder cancer: study protocol for a phase Ib/randomised IIa open label clinical trial.
Crabb S, Danson SJ, Catto JWF, McDowell C, Lowder JN, Caddy J, Dunkley D, Rajaram J, Ellis D, Hill S, Hathorn D, Whitehead A, Kalevras M, Huddart R, Griffiths G. Crabb S, et al. Trials. 2018 Apr 3;19(1):216. doi: 10.1186/s13063-018-2586-7. Trials. 2018. PMID: 29615077 Free PMC article.
Based on supportive pre-clinical data, we hypothesised that DNA methyltransferase inhibition would circumvent cisplatin resistance in UBC and potentially other cancers. METHODS: The addition of SGI-110 (guadecitabine, a DNA methyltransferase inhibitor) to con …
Based on supportive pre-clinical data, we hypothesised that DNA methyltransferase inhibition would circumvent cisplatin resistance in UBC an …
Clinical update on hypomethylating agents.
Duchmann M, Itzykson R. Duchmann M, et al. Int J Hematol. 2019 Aug;110(2):161-169. doi: 10.1007/s12185-019-02651-9. Epub 2019 Apr 24. Int J Hematol. 2019. PMID: 31020568 Review.
Immunomodulatory activity of SGI-110, a 5-aza-2'-deoxycytidine-containing demethylating dinucleotide.
Coral S, Parisi G, Nicolay HJ, Colizzi F, Danielli R, Fratta E, Covre A, Taverna P, Sigalotti L, Maio M. Coral S, et al. Cancer Immunol Immunother. 2013 Mar;62(3):605-14. doi: 10.1007/s00262-012-1365-7. Epub 2012 Nov 9. Cancer Immunol Immunother. 2013. PMID: 23138873
EXPERIMENTAL DESIGN: Cutaneous melanoma, mesothelioma, renal cell carcinoma, and sarcoma cells were treated in vitro with SGI-110. RT-PCR, quantitative RT-PCR, quantitative methylation-specific PCR, and flow cytometric analyses were performed to investigate changes …
EXPERIMENTAL DESIGN: Cutaneous melanoma, mesothelioma, renal cell carcinoma, and sarcoma cells were treated in vitro with SGI-110
SGI-110: DNA Methyltransferase Inhibitor Oncolytic.
Griffiths EA, Choy G, Redkar S, Taverna P, Azab M, Karpf AR. Griffiths EA, et al. Drugs Future. 2013 Aug;38(8):535-543. Drugs Future. 2013. PMID: 26190889 Free PMC article.
SGI-110 is a second-generation hypomethylating prodrug whose active metabolite is the well-characterized drug decitabine. ...
SGI-110 is a second-generation hypomethylating prodrug whose active metabolite is the well-characterized drug decitabine. ...
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