Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTELHN9L)

• DOT Name: Olfactomedin-4 (OLFM4)
• Synonyms: OLM4; Antiapoptotic protein GW112; G-CSF-stimulated clone 1 protein; hGC-1; hOLfD
• Gene Name: OLFM4
• UniProt ID: OLFM4_HUMAN
• Pfam ID: PF02191
• Sequence:
  MRPGLSFLLALLFFLGQAAGDLGDVGPPIPSPGFSSFPGVDSSSSFSSSSRSGSSSSRSL
  GSGGSVSQLFSNFTGSVDDRGTCQCSVSLPDTTFPVDRVERLEFTAHVLSQKFEKELSKV
  REYVQLISVYEKKLLNLTVRIDIMEKDTISYTELDFELIKVEVKEMEKLVIQLKESFGGS
  SEIVDQLEVEIRNMTLLVEKLETLDKNNVLAIRREIVALKTKLKECEASKDQNTPVVHPP
  PTPGSCGHGGVVNISKPSVVQLNWRGFSYLYGAWGRDYSPQHPNKGLYWVAPLNTDGRLL
  EYYRLYNTLDDLLLYINARELRITYGQGSGTAVYNNNMYVNMYNTGNIARVNLTTNTIAV
  TQTLPNAAYNNRFSYANVAWQDIDFAVDENGLWVIYSTEASTGNMVISKLNDTTLQVLNT
  WYTKQYKPSASNAFMVCGVLYATRTMNTRTEEIFYYYDTNTGKEGKLDIVMHKMQEKVQS
  INYNPFDQKLYVYNDGYLLNYDLSVLQKPQ
• Function: May promote proliferation of pancreatic cancer cells by favoring the transition from the S to G2/M phase. In myeloid leukemic cell lines, inhibits cell growth and induces cell differentiation and apoptosis. May play a role in the inhibition of EIF4EBP1 phosphorylation/deactivation. Facilitates cell adhesion, most probably through interaction with cell surface lectins and cadherin.
• Tissue Specificity: Expressed during myeloid lineage development. Much higher expression in bone marrow neutrophils than in peripheral blood neutrophils (at protein level). Strongly expressed in the prostate, small intestine and colon and moderately expressed in the bone marrow and stomach. Overexpressed in some pancreatic cancer tissues.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

2 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 Olfactomedin-4 (OLFM4).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Olfactomedin-4 (OLFM4).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Olfactomedin-4 (OLFM4).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Olfactomedin-4 (OLFM4).	[3]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Olfactomedin-4 (OLFM4).	[4]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Olfactomedin-4 (OLFM4).	[5]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Olfactomedin-4 (OLFM4).	[6]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Olfactomedin-4 (OLFM4).	[3]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Olfactomedin-4 (OLFM4).	[8]

References

• [1] 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.
• [2] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [3] Olfactomedin-4 regulation by estrogen in the human endometrium requires epidermal growth factor signaling. Am J Pathol. 2010 Nov;177(5):2495-508. doi: 10.2353/ajpath.2010.100026.
• [4] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [5] SGK1, a potential regulator of c-fms related breast cancer aggressiveness. Clin Exp Metastasis. 2004;21(6):477-83.
• [6] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [7] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [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.