Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK9F0LX)

• DOT Name: Early placenta insulin-like peptide (INSL4)
• Synonyms: EPIL; Insulin-like peptide 4; Placentin
• Gene Name: INSL4
• Related Disease:
  Advanced cancer
  Breast neoplasm
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Trichohepatoenteric syndrome
  Choriocarcinoma
  Fetal growth restriction
• UniProt ID: INSL4_HUMAN
• Sequence:
  MASLFRSYLPAIWLLLSQLLRESLAAELRGCGPRFGKHLLSYCPMPEKTFTTTPGGWLLE
  SGRPKEMVSTSNNKDGQALGTTSEFIPNLSPELKKPLSEGQPSLKKIILSRKKRSGRHRF
  DPFCCEVICDDGTSVKLCT
• Function: May play an important role in trophoblast development and in the regulation of bone formation.
• Tissue Specificity: Expressed in placenta, uterus and in fetal perichondrium. Expression levels were increased in both early placentas and molar pregnancies and were reduced in choriocarcinoma cells.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[2]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[1]
Lung cancer	DISCM4YA	Strong	Biomarker	[1]
Lung carcinoma	DISTR26C	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[1]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Biomarker	[3]
Choriocarcinoma	DISDBVNL	moderate	Altered Expression	[4]
Fetal growth restriction	DIS5WEJ5	moderate	Altered Expression	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Early placenta insulin-like peptide (INSL4).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Early placenta insulin-like peptide (INSL4).	[7]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Early placenta insulin-like peptide (INSL4).	[8]

References

• [1] Role of INSL4 Signaling in Sustaining the Growth and Viability of LKB1-Inactivated Lung Cancer.J Natl Cancer Inst. 2019 Jul 1;111(7):664-674. doi: 10.1093/jnci/djy166.
• [2] [Expression of early placenta insulin-like growth factor (EPIL) in breast cancer cells provides an autocrine loop with enhancement of predominantly HER-2-related invasivity].Verh Dtsch Ges Pathol. 2005;89:201-6.
• [3] The INSL4 gene maps close to WI-5527 at 9p24.1-->p23.3 clustered with two relaxin genes and outside the critical region for the monosomy 9p syndrome.Cytogenet Cell Genet. 1998;81(3-4):275-7. doi: 10.1159/000015045.
• [4] Transcriptional expression of genes involved in cell invasion and migration by normal and tumoral trophoblast cells.J Clin Endocrinol Metab. 2002 Nov;87(11):5336-9. doi: 10.1210/jc.2002-021093.
• [5] Early placental insulin-like protein (INSL4 or EPIL) in placental and fetal membrane growth.Biol Reprod. 2005 Oct;73(4):695-702. doi: 10.1095/biolreprod.105.039859. Epub 2005 Jun 15.
• [6] 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.
• [7] Gene expression profiling of A549 cells exposed to Milan PM2.5. Toxicol Lett. 2012 Mar 7;209(2):136-45.
• [8] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.