Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTTPU1G)

• DTT Name: Apoptosis inhibitor survivin (BIRC5)
• Synonyms: Survivin; IAP4; Baculoviral IAP repeat-containing protein 5; Apoptosis inhibitor 4; API4
• Gene Name: BIRC5
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Acyltransferase
• UniProt ID: BIRC5_HUMAN
• TTD ID: T02677
• Sequence:
  MGAPTLPPAWQPFLKDHRISTFKNWPFLEGCACTPERMAEAGFIHCPTENEPDLAQCFFC
  FKELEGWEPDDDPIEEHKKHSSGCAFLSVKKQFEELTLGEFLKLDRERAKNKIAKETNNK
  KKEFEETAKKVRRAIEQLAAMD
• Function: Component of a chromosome passage protein complex (CPC) which is essential for chromosome alignment and segregation during mitosis and cytokinesis. Acts as an important regulator of the localization of this complex; directs CPC movement to different locations from the inner centromere during prometaphase to midbody during cytokinesis and participates in the organization of the center spindle by associating with polymerized microtubules. Involved in the recruitment of CPC to centromeres during early mitosis via association with histone H3 phosphorylated at 'Thr-3' (H3pT3) during mitosis. The complex with RAN plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules. May counteract a default induction of apoptosis in G2/M phase. The acetylated form represses STAT3 transactivation of target gene promoters. May play a role in neoplasia. Inhibitor of CASP3 and CASP7. Isoform 2 and isoform 3 do not appear to play vital roles in mitosis. Isoform 3 shows a marked reduction in its anti-apoptotic effects when compared with the displayed wild-type isoform. Multitasking protein that has dual roles in promoting cell proliferation and preventing apoptosis.
• KEGG Pathway:
  Hippo signaling pathway (hsa04390)
  Hepatitis B (hsa05161)
  Pathways in cancer (hsa05200)
  Colorectal cancer (hsa05210)
• Reactome Pathway:
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  RHO GTPases Activate Formins (R-HSA-5663220)
  Mitotic Prometaphase (R-HSA-68877)
  Separation of Sister Chromatids (R-HSA-2467813)

Molecular Interaction Atlas (MIA) of This DTT

4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ISIS 23722	DMQZI7K	Solid tumour/cancer	2A00-2F9Z	Phase 3	[1]
SurVaxM	DMAIGTE	Glioblastoma of brain	2A00.00	Phase 2	[2]
CV-9201	DMCPZYT	Non-small-cell lung cancer	2C25.Y	Phase 1/2	[3]
EZN-3042	DMXFY18	Solid tumour/cancer	2A00-2F9Z	Phase 1	[4]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Lung cancer	2C82	Lung tissue	1.67E-190	1.63	5.29
Ovarian cancer	2C82	Ovarian tissue	6.97E-05	1.62	2.68

References

• [1] Targeted BIRC5 silencing using YM155 causes cell death in neuroblastoma cells with low ABCB1 expression.Eur J Cancer.2012 Mar;48(5):763-71.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] National Cancer Institute Drug Dictionary (drug id 648549).
• [4] SPC3042: a proapoptotic survivin inhibitor.Mol Cancer Ther.2008 Sep;7(9):2736-45.