Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEY2UQA)

• DOT Name: Maternal embryonic leucine zipper kinase (MELK)
• Synonyms: hMELK; EC 2.7.11.1; Protein kinase Eg3; pEg3 kinase; Protein kinase PK38; hPK38; Tyrosine-protein kinase MELK; EC 2.7.10.2
• Gene Name: MELK
• UniProt ID: MELK_HUMAN
• PDB ID: 4BKY; 4BKZ; 4BL1; 4D2P; 4D2T; 4D2V; 4D2W; 4IXP; 4UMP; 4UMQ; 4UMR; 4UMT; 4UMU; 5IH8; 5IH9; 5IHA; 5IHC; 5K00; 5M5A; 5MAF; 5MAG; 5MAH; 5MAI; 5TVT; 5TWL; 5TWU; 5TWY; 5TWZ; 5TX3; 6GVX; 6VXR
• EC Number: 2.7.10.2; 2.7.11.1
• Pfam ID: PF02149 ; PF21594 ; PF00069
• Sequence:
  MKDYDELLKYYELHETIGTGGFAKVKLACHILTGEMVAIKIMDKNTLGSDLPRIKTEIEA
  LKNLRHQHICQLYHVLETANKIFMVLEYCPGGELFDYIISQDRLSEEETRVVFRQIVSAV
  AYVHSQGYAHRDLKPENLLFDEYHKLKLIDFGLCAKPKGNKDYHLQTCCGSLAYAAPELI
  QGKSYLGSEADVWSMGILLYVLMCGFLPFDDDNVMALYKKIMRGKYDVPKWLSPSSILLL
  QQMLQVDPKKRISMKNLLNHPWIMQDYNYPVEWQSKNPFIHLDDDCVTELSVHHRNNRQT
  MEDLISLWQYDHLTATYLLLLAKKARGKPVRLRLSSFSCGQASATPFTDIKSNNWSLEDV
  TASDKNYVAGLIDYDWCEDDLSTGAATPRTSQFTKYWTESNGVESKSLTPALCRTPANKL
  KNKENVYTPKSAVKNEEYFMFPEPKTPVNKNQHKREILTTPNRYTTPSKARNQCLKETPI
  KIPVNSTGTDKLMTGVISPERRCRSVELDLNQAHMEETPKRKGAKVFGSLERGLDKVITV
  LTRSKRKGSARDGPRRLKLHYNVTTTRLVNPDQLLNEIMSILPKKHVDFVQKGYTLKCQT
  QSDFGKVTMQFELEVCQLQKPDVVGIRRQRLKGDAWVYKRLVEDILSSCKV
• Function: Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis.
• Tissue Specificity: Expressed in placenta, kidney, thymus, testis, ovary and intestine.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Maternal embryonic leucine zipper kinase (MELK) affects the response to substance of Fluorouracil.	[29]
Vinblastine	DM5TVS3	Approved	Maternal embryonic leucine zipper kinase (MELK) affects the response to substance of Vinblastine.	[30]

28 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Maternal embryonic leucine zipper kinase (MELK).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Maternal embryonic leucine zipper kinase (MELK).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Maternal embryonic leucine zipper kinase (MELK).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Maternal embryonic leucine zipper kinase (MELK).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Maternal embryonic leucine zipper kinase (MELK).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Maternal embryonic leucine zipper kinase (MELK).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Maternal embryonic leucine zipper kinase (MELK).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Maternal embryonic leucine zipper kinase (MELK).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Maternal embryonic leucine zipper kinase (MELK).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Maternal embryonic leucine zipper kinase (MELK).	[10]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Maternal embryonic leucine zipper kinase (MELK).	[10]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Maternal embryonic leucine zipper kinase (MELK).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Maternal embryonic leucine zipper kinase (MELK).	[12]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Maternal embryonic leucine zipper kinase (MELK).	[13]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Maternal embryonic leucine zipper kinase (MELK).	[14]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Maternal embryonic leucine zipper kinase (MELK).	[15]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Maternal embryonic leucine zipper kinase (MELK).	[16]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Maternal embryonic leucine zipper kinase (MELK).	[17]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Maternal embryonic leucine zipper kinase (MELK).	[18]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Maternal embryonic leucine zipper kinase (MELK).	[8]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Maternal embryonic leucine zipper kinase (MELK).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Maternal embryonic leucine zipper kinase (MELK).	[20]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Maternal embryonic leucine zipper kinase (MELK).	[21]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Maternal embryonic leucine zipper kinase (MELK).	[23]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Maternal embryonic leucine zipper kinase (MELK).	[25]
EMODIN	DMAEDQG	Terminated	EMODIN decreases the expression of Maternal embryonic leucine zipper kinase (MELK).	[26]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Maternal embryonic leucine zipper kinase (MELK).	[28]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Maternal embryonic leucine zipper kinase (MELK).	[18]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Maternal embryonic leucine zipper kinase (MELK).	[22]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Maternal embryonic leucine zipper kinase (MELK).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Maternal embryonic leucine zipper kinase (MELK).	[27]

References

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