Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN36T21)

• DOT Name: Lactase-like protein (LCTL)
• Synonyms: Klotho/lactase-phlorizin hydrolase-related protein
• Gene Name: LCTL
• Related Disease:
  Knee osteoarthritis
  Osteoarthritis
• UniProt ID: LCTL_HUMAN
• Pfam ID: PF00232
• Sequence:
  MKPVWVATLLWMLLLVPRLGAARKGSPEEASFYYGTFPLGFSWGVGSSAYQTEGAWDQDG
  KGPSIWDVFTHSGKGKVLGNETADVACDGYYKVQEDIILLRELHVNHYRFSLSWPRLLPT
  GIRAEQVNKKGIEFYSDLIDALLSSNITPIVTLHHWDLPQLLQVKYGGWQNVSMANYFRD
  YANLCFEAFGDRVKHWITFSDPRAMAEKGYETGHHAPGLKLRGTGLYKAAHHIIKAHAKA
  WHSYNTTWRSKQQGLVGISLNCDWGEPVDISNPKDLEAAERYLQFCLGWFANPIYAGDYP
  QVMKDYIGRKSAEQGLEMSRLPVFSLQEKSYIKGTSDFLGLGHFTTRYITERNYPSRQGP
  SYQNDRDLIELVDPNWPDLGSKWLYSVPWGFRRLLNFAQTQYGDPPIYVMENGASQKFHC
  TQLCDEWRIQYLKGYINEMLKAIKDGANIKGYTSWSLLDKFEWEKGYSDRYGFYYVEFND
  RNKPRYPKASVQYYKKIIIANGFPNPREVESWYLKALETCSINNQMLAAEPLLSHMQMVT
  EIVVPTVCSLCVLITAVLLMLLLRRQS
• Function: Plays a role in formation of the lens suture in the eye, which is important for normal optical properties of the lens.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Knee osteoarthritis	DISLSNBJ	Definitive	Genetic Variation	[1]
Osteoarthritis	DIS05URM	moderate	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Lactase-like protein (LCTL).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Lactase-like protein (LCTL).	[4]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Lactase-like protein (LCTL).	[5]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Lactase-like protein (LCTL).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Lactase-like protein (LCTL).	[6]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Lactase-like protein (LCTL).	[7]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Lactase-like protein (LCTL).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Lactase-like protein (LCTL).	[8]

References

• [1] A naturally aging knee, or development of early knee osteoarthritis?.Osteoarthritis Cartilage. 2018 Nov;26(11):1447-1452. doi: 10.1016/j.joca.2018.04.020. Epub 2018 Jul 21.
• [2] A quantitative metric for knee osteoarthritis: reference values of joint space loss.Osteoarthritis Cartilage. 2018 Sep;26(9):1215-1224. doi: 10.1016/j.joca.2018.05.014. Epub 2018 May 26.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [7] 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.
• [8] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.