Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTCJUR4)

• DTT Name: Exportin-1 (XPO1)
• Synonyms: Exp1; Chromosome region maintenance 1 protein homolog; CRM1
• Gene Name: XPO1
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Eukaryotic nuclear pore complex
• UniProt ID: XPO1_HUMAN
• TTD ID: T51407
• Sequence:
  MPAIMTMLADHAARQLLDFSQKLDINLLDNVVNCLYHGEGAQQRMAQEVLTHLKEHPDAW
  TRVDTILEFSQNMNTKYYGLQILENVIKTRWKILPRNQCEGIKKYVVGLIIKTSSDPTCV
  EKEKVYIGKLNMILVQILKQEWPKHWPTFISDIVGASRTSESLCQNNMVILKLLSEEVFD
  FSSGQITQVKSKHLKDSMCNEFSQIFQLCQFVMENSQNAPLVHATLETLLRFLNWIPLGY
  IFETKLISTLIYKFLNVPMFRNVSLKCLTEIAGVSVSQYEEQFVTLFTLTMMQLKQMLPL
  NTNIRLAYSNGKDDEQNFIQNLSLFLCTFLKEHDQLIEKRLNLRETLMEALHYMLLVSEV
  EETEIFKICLEYWNHLAAELYRESPFSTSASPLLSGSQHFDVPPRRQLYLPMLFKVRLLM
  VSRMAKPEEVLVVENDQGEVVREFMKDTDSINLYKNMRETLVYLTHLDYVDTERIMTEKL
  HNQVNGTEWSWKNLNTLCWAIGSISGAMHEEDEKRFLVTVIKDLLGLCEQKRGKDNKAII
  ASNIMYIVGQYPRFLRAHWKFLKTVVNKLFEFMHETHDGVQDMACDTFIKIAQKCRRHFV
  QVQVGEVMPFIDEILNNINTIICDLQPQQVHTFYEAVGYMIGAQTDQTVQEHLIEKYMLL
  PNQVWDSIIQQATKNVDILKDPETVKQLGSILKTNVRACKAVGHPFVIQLGRIYLDMLNV
  YKCLSENISAAIQANGEMVTKQPLIRSMRTVKRETLKLISGWVSRSNDPQMVAENFVPPL
  LDAVLIDYQRNVPAAREPEVLSTMAIIVNKLGGHITAEIPQIFDAVFECTLNMINKDFEE
  YPEHRTNFFLLLQAVNSHCFPAFLAIPPTQFKLVLDSIIWAFKHTMRNVADTGLQILFTL
  LQNVAQEEAAAQSFYQTYFCDILQHIFSVVTDTSHTAGLTMHASILAYMFNLVEEGKIST
  SLNPGNPVNNQIFLQEYVANLLKSAFPHLQDAQVKLFVTGLFSLNQDIPAFKEHLRDFLV
  QIKEFAGEDTSDLFLEEREIALRQADEEKHKRQMSVPGIFNPHEIPEEMCD
• Function: In the nucleus, in association with RANBP3, binds cooperatively to the NES on its target protein and to the GTPase RAN in its active GTP-bound form (Ran-GTP). Docking of this complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, disassembling of the complex and hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause release of the cargo from the export receptor. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Involved in U3 snoRNA transport from Cajal bodies to nucleoli. Binds to late precursor U3 snoRNA bearing a TMG cap. Mediates the nuclear export of cellular proteins (cargos) bearing a leucine-rich nuclear export signal (NES) and of RNAs.
• KEGG Pathway:
  Ribosome biogenesis in eukaryotes (hsa03008)
  RNA transport (hsa03013)
  Influenza A (hsa05164)
  HTLV-I infection (hsa05166)
  Epstein-Barr virus infection (hsa05169)
• Reactome Pathway:
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  Deactivation of the beta-catenin transactivating complex (R-HSA-3769402)
  HuR (ELAVL1) binds and stabilizes mRNA (R-HSA-450520)
  RHO GTPases Activate Formins (R-HSA-5663220)
  Mitotic Prometaphase (R-HSA-68877)
  Cyclin A/B1 associated events during G2/M transition (R-HSA-69273)
  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
Selinexor	DMBD4K3	Multiple myeloma	2A83	Phase 3	[1]
Selinexor oral	DMDLOBZ	Recurrent glioblastoma	2A00.00	Phase 2	[2]
Eltanexor oral	DM7CLEZ	Colorectal cancer	2B91.Z	Phase 1/2	[3]
SL-801	DMIVGYK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
KOS-1815	DMCGFY6	Solid tumour/cancer	2A00-2F9Z	Preclinical	[1]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Octahydrocurcumin	DMUFDR6	Solid tumour/cancer	2A00-2F9Z	Investigative	[4]
S109	DM2JYQA	Solid tumour/cancer	2A00-2F9Z	Investigative	[5]

References

• [1] Inhibition of CRM1-dependent nuclear export sensitizes malignant cells to cytotoxic and targeted agents. Semin Cancer Biol. 2014 August; 0: 62-73.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] Therapeutic strategies targeting FOXO transcription factors. Nat Rev Drug Discov. 2021 Jan;20(1):21-38.
• [5] Reversible inhibitor of CRM1 sensitizes glioblastoma cells to radiation by blocking the NF-B signaling pathway. Cancer Cell Int. 2020 Mar 30;20:97.