Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTTRP0H)

• DTT Name: Kinesin-like protein KIF11 (KIF11)
• Synonyms: Thyroid receptor interacting protein 5; TRIP5; Kinesin-related motor protein Eg5; Kinesin-like spindle protein HKSP; Kinesin-like protein 1; KIF11; Eg5
• Gene Name: KIF11
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Kinesin-like protein family
• UniProt ID: KIF11_HUMAN
• TTD ID: T28484
• Sequence:
  MASQPNSSAKKKEEKGKNIQVVVRCRPFNLAERKASAHSIVECDPVRKEVSVRTGGLADK
  SSRKTYTFDMVFGASTKQIDVYRSVVCPILDEVIMGYNCTIFAYGQTGTGKTFTMEGERS
  PNEEYTWEEDPLAGIIPRTLHQIFEKLTDNGTEFSVKVSLLEIYNEELFDLLNPSSDVSE
  RLQMFDDPRNKRGVIIKGLEEITVHNKDEVYQILEKGAAKRTTAATLMNAYSSRSHSVFS
  VTIHMKETTIDGEELVKIGKLNLVDLAGSENIGRSGAVDKRAREAGNINQSLLTLGRVIT
  ALVERTPHVPYRESKLTRILQDSLGGRTRTSIIATISPASLNLEETLSTLEYAHRAKNIL
  NKPEVNQKLTKKALIKEYTEEIERLKRDLAAAREKNGVYISEENFRVMSGKLTVQEEQIV
  ELIEKIGAVEEELNRVTELFMDNKNELDQCKSDLQNKTQELETTQKHLQETKLQLVKEEY
  ITSALESTEEKLHDAASKLLNTVEETTKDVSGLHSKLDRKKAVDQHNAEAQDIFGKNLNS
  LFNNMEELIKDGSSKQKAMLEVHKTLFGNLLSSSVSALDTITTVALGSLTSIPENVSTHV
  SQIFNMILKEQSLAAESKTVLQELINVLKTDLLSSLEMILSPTVVSILKINSQLKHIFKT
  SLTVADKIEDQKKELDGFLSILCNNLHELQENTICSLVESQKQCGNLTEDLKTIKQTHSQ
  ELCKLMNLWTERFCALEEKCENIQKPLSSVQENIQQKSKDIVNKMTFHSQKFCADSDGFS
  QELRNFNQEGTKLVEESVKHSDKLNGNLEKISQETEQRCESLNTRTVYFSEQWVSSLNER
  EQELHNLLEVVSQCCEASSSDITEKSDGRKAAHEKQHNIFLDQMTIDEDKLIAQNLELNE
  TIKIGLTKLNCFLEQDLKLDIPTGTTPQRKSYLYPSTLVRTEPREHLLDQLKRKQPELLM
  MLNCSENNKEETIPDVDVEEAVLGQYTEEPLSQEPSVDAGVDCSSIGGVPFFQHKKSHGK
  DKENRGINTLERSKVEETTEHLVTKSRLPLRAQINL
• Function: Motor protein required for establishing a bipolar spindle. Blocking of KIF11 prevents centrosome migration and arrest cells in mitosis with monoastral microtubule arrays.
• Reactome Pathway:
  Kinesins (R-HSA-983189)
  MHC class II antigen presentation (R-HSA-2132295)

Molecular Interaction Atlas (MIA) of This DTT

8 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ARRY-520	DMTOI7S	Multiple myeloma	2A83	Phase 2	[1]
AZD-4877	DMFVL5J	Acute myeloid leukaemia	2A60	Phase 2	[2]
Ispinesib	DMP2BWX	Head and neck cancer	2D42	Phase 2	[3]
LY2523355	DMCV602	Acute myeloid leukaemia	2A60	Phase 2	[2]
SB-743921	DM6XJ9S	Solid tumour/cancer	2A00-2F9Z	Phase 2	[4]
4SC-205	DMG75P3	Lymphoma	2A80-2A86	Phase 1	[5]
ARQ 621	DMCRLQZ	Haematological malignancy	2B33.Y	Phase 1	[2]
MK-0731	DM2TAUR	Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Monastrol	DMLSEJN	Discovery agent	N.A.	Investigative	[6]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2C82	Bone marrow	5.72E-26	-1.17	-1.31

References

• [1] Inhibition of KSP by ARRY-520 induces cell cycle block and cell death via the mitochondrial pathway in AML cells. Leukemia. 2009 Oct;23(10):1755-62.
• [2] Kinesins and cancer. Nat Rev Cancer. 2012 Jul 24;12(8):527-39.
• [3] Initial testing (stage 1) of the kinesin spindle protein inhibitor ispinesib by the pediatric preclinical testing program. Pediatr Blood Cancer. 2009 Dec 15;53(7):1255-63.
• [4] Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2009 Jan-Feb;31(1):47-57.
• [5] 2011 Pipeline of 4SC AG.
• [6] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.