Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT0J32Z)

• DTT Name: Smad7 messenger RNA (Smad7 mRNA)
• Synonyms: hSMAD7 (mRNA); Smad7 (mRNA); SMAD family member 7 (mRNA); SMAD 7 (mRNA); Mothers against decapentaplegic homolog 8 (mRNA); Mothers against decapentaplegic homolog 7 (mRNA); Mothers against DPP homolog 8 (mRNA); Mothers against DPP homolog 7 (mRNA); MADH8 (mRNA); MADH7 (mRNA); MAD homolog 8 (mRNA); MAD homolog 7 (mRNA)
• Gene Name: SMAD7
• DTT Type: Clinical trial target; [1]
• BioChemical Class: mRNA target
• UniProt ID: SMAD7_HUMAN
• TTD ID: T93661
• Sequence:
  MFRTKRSALVRRLWRSRAPGGEDEEEGAGGGGGGGELRGEGATDSRAHGAGGGGPGRAGC
  CLGKAVRGAKGHHHPHPPAAGAGAAGGAEADLKALTHSVLKKLKERQLELLLQAVESRGG
  TRTACLLLPGRLDCRLGPGAPAGAQPAQPPSSYSLPLLLCKVFRWPDLRHSSEVKRLCCC
  ESYGKINPELVCCNPHHLSRLCELESPPPPYSRYPMDFLKPTADCPDAVPSSAETGGTNY
  LAPGGLSDSQLLLEPGDRSHWCVVAYWEEKTRVGRLYCVQEPSLDIFYDLPQGNGFCLGQ
  LNSDNKSQLVQKVRSKIGCGIQLTREVDGVWVYNRSSYPIFIKSATLDNPDSRTLLVHKV
  FPGFSIKAFDYEKAYSLQRPNDHEFMQQPWTGFTVQISFVKGWGQCYTRQFISSCPCWLE
  VIFNSR
• Function: Functions as an adapter to recruit SMURF2 to the TGF-beta receptor complex. Also acts by recruiting the PPP1R15A-PP1 complex to TGFBR1, which promotes its dephosphorylation. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator. Antagonist of signaling by TGF-beta (transforming growth factor) type 1 receptor superfamily members; has been shown to inhibit TGF-beta (Transforming growth factor) and activin signaling by associating with their receptors thus preventing SMAD2 access.
• KEGG Pathway:
  Endocytosis (hsa04144)
  TGF-beta signaling pathway (hsa04350)
  Hippo signaling pathway (hsa04390)
• Reactome Pathway: SMAD2/SMAD3 (R-HSA-2173796)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GED-0301	DMTUV7L	Crohn disease	DD70	Phase 3	[1]

4 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ISIS 28465	DMQ5JNT	Discovery agent	N.A.	Investigative	[2]
ISIS 28466	DMH96UP	Discovery agent	N.A.	Investigative	[2]
ISIS 28472	DMA4U2P	Discovery agent	N.A.	Investigative	[2]
ISIS 28477	DMMOV9U	Discovery agent	N.A.	Investigative	[2]

References

• [1] A phase 1 open-label trial shows that smad7 antisense oligonucleotide (GED0301) does not increase the risk of small bowel strictures in Crohn's disease. Aliment Pharmacol Ther. 2012 Nov;36(9):850-7.
• [2] US patent application no. 6,159,697, Antisense modulation of Smad7 expression.