Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTRE6AX)

• DTT Name: Bcl-x messenger RNA (BCL2L1 mRNA)
• Synonyms: Bcl2like protein 1 (mRNA); Bcl2L1 (mRNA); Bcl2-L-1 (mRNA); Bcl-XL (mRNA); Bcl-2-like protein 1 (mRNA); BCLX (mRNA); BCL2L (mRNA); Apoptosis regulator Bcl-X (mRNA)
• Gene Name: BCL2L1
• DTT Type: Literature-reported target; [1]
• BioChemical Class: mRNA target
• UniProt ID: B2CL1_HUMAN
• TTD ID: T19923
• Sequence:
  MSQSNRELVVDFLSYKLSQKGYSWSQFSDVEENRTEAPEGTESEMETPSAINGNPSWHLA
  DSPAVNGATGHSSSLDAREVIPMAAVKQALREAGDEFELRYRRAFSDLTSQLHITPGTAY
  QSFEQVVNELFRDGVNWGRIVAFFSFGGALCVESVDKEMQVLVSRIAAWMATYLNDHLEP
  WIQENGGWDTFVELYGNNAAAESRKGQERFNRWFLTGMTVAGVVLLGSLFSRK
• Function: Inhibits activation of caspases. Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis. Potent inhibitor of cell death.
• KEGG Pathway:
  Ras signaling pathway (hsa04014)
  NF-kappa B signaling pathway (hsa04064)
  PI3K-Akt signaling pathway (hsa04151)
  Apoptosis (hsa04210)
  Jak-STAT signaling pathway (hsa04630)
  Amyotrophic lateral sclerosis (ALS) (hsa05014)
  Toxoplasmosis (hsa05145)
  HTLV-I infection (hsa05166)
  Pathways in cancer (hsa05200)
  Transcriptional misregulation in cancer (hsa05202)
  Pancreatic cancer (hsa05212)
  Chronic myeloid leukemia (hsa05220)
  Small cell lung cancer (hsa05222)
• Reactome Pathway:
  The NLRP1 inflammasome (R-HSA-844455)
  BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members (R-HSA-111453)

Molecular Interaction Atlas (MIA) of This DTT

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PURPUROGALLIN	DM63O4F	N. A.	N. A.	Terminated	[1]

13 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
4,5-dibenzylbenzene-1,2-diol	DMHURXY	Discovery agent	N.A.	Investigative	[2]
ISIS 11219	DMW3145	Discovery agent	N.A.	Investigative	[3]
ISIS 11220	DMNJS0K	Discovery agent	N.A.	Investigative	[3]
ISIS 11221	DMDUIG3	Discovery agent	N.A.	Investigative	[3]
ISIS 11223	DM7LPI4	Discovery agent	N.A.	Investigative	[3]
ISIS 11224	DMMGA6K	Discovery agent	N.A.	Investigative	[3]
ISIS 15998	DMAQ9EB	Discovery agent	N.A.	Investigative	[3]
ISIS 15999	DMMEP6J	Discovery agent	N.A.	Investigative	[3]
ISIS 16005	DMDORHA	Discovery agent	N.A.	Investigative	[3]
ISIS 16009	DMBRKFC	Discovery agent	N.A.	Investigative	[3]
ISIS 16010	DMZID0W	Discovery agent	N.A.	Investigative	[3]
QEDIIRNIARHLAQVGDSMDR	DMJ38YV	Discovery agent	N.A.	Investigative	[4]
TW-37	DMDE8YS	Discovery agent	N.A.	Investigative	[5]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Lung cancer	2C82	Lung tissue	7.28E-13	-0.55	-0.68

References

• [1] Discovery, characterization, and structure-activity relationships studies of proapoptotic polyphenols targeting B-cell lymphocyte/leukemia-2 proteins. J Med Chem. 2003 Sep 25;46(20):4259-64.
• [2] Vaccinia virus virulence factor N1L is a novel promising target for antiviral therapeutic intervention. J Med Chem. 2010 May 27;53(10):3899-906.
• [3] US patent application no. 7,148,204, Antisense modulation of bcl-x expression.
• [4] Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins. J Med Chem. 2006 Oct 19;49(21):6139-42.
• [5] Fragment-based deconstruction of Bcl-xL inhibitors. J Med Chem. 2010 Mar 25;53(6):2577-88.