Synonyms: DNA, d(P-thio)(G-T-m5C-G-C-C-C-C-T-T-C-T-C-C-C-m5C-G-C-A-G-C) | GED-0301 | GED0301
Compound class:
Synthetic organic
Comment: Mongersen (GED-0301) is a phosphorothioate single-stranded oligonucleotide matching the region 107-128 (5'-GCTGCGGGGAGAAGGGGCGAC-3') of the human Smad7 complementary DNA sequence. The antisense oligonucleotide sequence is (3'-5')d(P-thio)(G-T-m5C-G-C-C-C-C-T-T-C-T-C-C-C-m5C-G-C-A-G-C), where m5C represents 2'-deoxy-5-methyl-P-thiocytidylyl bases.
Mongersen was investigated as a treatment for Smad7-induced colitis associated with Crohn's disease and irritable bowel disease (IBD), but following failure to demonstrate efficacy in Phase 3 evaluation, development was terminated in late 2017. |
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References |
1. Boirivant M, Pallone F, Di Giacinto C, Fina D, Monteleone I, Marinaro M, Caruso R, Colantoni A, Palmieri G, Sanchez M et al.. (2006)
Inhibition of Smad7 with a specific antisense oligonucleotide facilitates TGF-beta1-mediated suppression of colitis. Gastroenterology, 131 (6): 1786-98. [PMID:17087939] |
2. Monteleone G, Kumberova A, Croft NM, McKenzie C, Steer HW, MacDonald TT. (2001)
Blocking Smad7 restores TGF-beta1 signaling in chronic inflammatory bowel disease. J Clin Invest, 108 (4): 601-9. [PMID:11518734] |
3. Monteleone G, Neurath MF, Ardizzone S, Di Sabatino A, Fantini MC, Castiglione F, Scribano ML, Armuzzi A, Caprioli F, Sturniolo GC et al.. (2015)
Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn's disease. N Engl J Med, 372 (12): 1104-13. [PMID:25785968] |
4. Trivedi PJ, Adams DH. (2018)
Chemokines and Chemokine Receptors as Therapeutic Targets in Inflammatory Bowel Disease; Pitfalls and Promise. J Crohns Colitis, 12 (suppl_2): S641-S652. [PMID:30137309] |