Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZGAZ79)

• DOT Name: ALK and LTK ligand 1 (ALKAL1)
• Synonyms: Augmentor beta; AUG-beta
• Gene Name: ALKAL1
• Related Disease: Clear cell renal carcinoma
• UniProt ID: ALKL1_HUMAN
• PDB ID: 7MK7; 7MZZ; 7NX0
• Pfam ID: PF15129
• Sequence:
  MRPLKPGAPLPALFLLALALSPHGAHGRPRGRRGARVTDKEPKPLLFLPAAGAGRTPSGS
  RSAEIFPRDSNLKDKFIKHFTGPVTFSPECSKHFHRLYYNTRECSTPAYYKRCARLLTRL
  AVSPLCSQT
• Function: Cytokine that acts as a physiological ligand for receptor tyrosine kinase LTK, leading to its activation. Monomeric ALKAL1 binds to LTK, leading to LTK homodimerization and activation. In contrast to ALKAL2, does not act as a potent physiological ligand for ALK.
• Tissue Specificity: Widely expressed with highest levels in thyroid and moderate levels in stomach, trachea, small intestine, prostate and brain.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Clear cell renal carcinoma	DISBXRFJ	moderate	Posttranslational Modification	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of ALK and LTK ligand 1 (ALKAL1).	[2]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of ALK and LTK ligand 1 (ALKAL1).	[3]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of ALK and LTK ligand 1 (ALKAL1).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of ALK and LTK ligand 1 (ALKAL1).	[5]

References

• [1] Novel method for DNA methylation analysis using high-performance liquid chromatography and its clinical application.Cancer Sci. 2018 May;109(5):1690-1700. doi: 10.1111/cas.13566. Epub 2018 Apr 17.
• [2] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [3] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [4] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [5] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.