Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ0TQ9T)

• DOT Name: Cyclin-dependent kinase-like 3 (CDKL3)
• Synonyms: EC 2.7.11.22; Serine/threonine-protein kinase NKIAMRE
• Gene Name: CDKL3
• Related Disease:
  Cholangiocarcinoma
  Esophageal squamous cell carcinoma
  Myelodysplastic syndrome
  Intellectual disability
• UniProt ID: CDKL3_HUMAN
• PDB ID: 3ZDU
• EC Number: 2.7.11.22
• Pfam ID: PF00069
• Sequence:
  MEMYETLGKVGEGSYGTVMKCKHKNTGQIVAIKIFYERPEQSVNKIAMREIKFLKQFHHE
  NLVNLIEVFRQKKKIHLVFEFIDHTVLDELQHYCHGLESKRLRKYLFQILRAIDYLHSNN
  IIHRDIKPENILVSQSGITKLCDFGFARTLAAPGDIYTDYVATRWYRAPELVLKDTSYGK
  PVDIWALGCMIIEMATGNPYLPSSSDLDLLHKIVLKVGNLSPHLQNIFSKSPIFAGVVLP
  QVQHPKNARKKYPKLNGLLADIVHACLQIDPADRISSSDLLHHEYFTRDGFIEKFMPELK
  AKLLQEAKVNSLIKPKESSKENELRKDERKTVYTNTLLSSSVLGKEIEKEKKPKEIKVRV
  IKVKGGRGDISEPKKKEYEGGLGQQDANENVHPMSPDTKLVTIEPPNPINPSTNCNGLKE
  NPHCGGSVTMPPINLTNSNLMAANLSSNLFHPSVRLTERAKKRRTSSQSIGQVMPNSRQE
  DPGPIQSQMEKGIFNERTGHSDQMANENKRKLNFSRSDRKEFHFPELPVTIQSKDTKGME
  VKQIKMLKRESKKTESSKIPTLLNVDQNQEKQEGGDGHCEGKNLKRNRFFFW

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[1]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[2]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[3]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Cyclin-dependent kinase-like 3 (CDKL3).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cyclin-dependent kinase-like 3 (CDKL3).	[6]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Cyclin-dependent kinase-like 3 (CDKL3).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cyclin-dependent kinase-like 3 (CDKL3).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Cyclin-dependent kinase-like 3 (CDKL3).	[9]

References

• [1] Curcumol Exerts Anticancer Effect in Cholangiocarcinoma Cells via Down-Regulating CDKL3.Front Physiol. 2018 Mar 20;9:234. doi: 10.3389/fphys.2018.00234. eCollection 2018.
• [2] Increased CDKL3 expression predicts poor prognosis and enhances malignant phenotypes in esophageal squamous cell carcinoma.J Cell Biochem. 2019 May;120(5):7174-7184. doi: 10.1002/jcb.27991. Epub 2018 Nov 1.
• [3] Identification of NKIAMRE, the human homologue to the mitogen-activated protein kinase-/cyclin-dependent kinase-related protein kinase NKIATRE, and its loss in leukemic blasts with chromosome arm 5q deletion.Cancer Res. 1999 Aug 15;59(16):4069-74.
• [4] Inactivation of the CDKL3 gene at 5q31.1 by a balanced t(X;5) translocation associated with nonspecific mild mental retardation.Am J Med Genet A. 2008 May 15;146A(10):1267-79. doi: 10.1002/ajmg.a.32274.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [7] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [8] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.