Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXPWJ56)

• DOT Name: CB1 cannabinoid receptor-interacting protein 1 (CNRIP1)
• Synonyms: CRIP-1
• Gene Name: CNRIP1
• Related Disease:
  B-cell lymphoma
  Colorectal carcinoma
  Autosomal dominant nonsyndromic hearing loss 58
  Psychotic disorder
  Schizophrenia
• UniProt ID: CNRP1_HUMAN
• Pfam ID: PF15043
• Sequence:
  MGDLPGLVRLSIALRIQPNDGPVFYKVDGQRFGQNRTIKLLTGSSYKVEVKIKPSTLQVE
  NISIGGVLVPLELKSKEPDGDRVVYTGTYDTEGVTPTKSGERQPIQITMPFTDIGTFETV
  WQVKFYNYHKRDHCQWGSPFSVIEYECKPNETRSLMWVNKESFL
• Function: [Isoform 1]: Suppresses cannabinoid receptor CNR1-mediated tonic inhibition of voltage-gated calcium channels; [Isoform 2]: Does not suppress cannabinoid receptor CNR1-mediated tonic inhibition of voltage-gated calcium channels.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Autosomal dominant nonsyndromic hearing loss 58	DISPDPK0	Limited	Autosomal dominant	[3]
Psychotic disorder	DIS4UQOT	Limited	Altered Expression	[4]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[4]

9 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 CB1 cannabinoid receptor-interacting protein 1 (CNRIP1).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of CB1 cannabinoid receptor-interacting protein 1 (CNRIP1).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of CB1 cannabinoid receptor-interacting protein 1 (CNRIP1).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of CB1 cannabinoid receptor-interacting protein 1 (CNRIP1).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of CB1 cannabinoid receptor-interacting protein 1 (CNRIP1).	[9]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of CB1 cannabinoid receptor-interacting protein 1 (CNRIP1).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of CB1 cannabinoid receptor-interacting protein 1 (CNRIP1).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of CB1 cannabinoid receptor-interacting protein 1 (CNRIP1).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of CB1 cannabinoid receptor-interacting protein 1 (CNRIP1).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of CB1 cannabinoid receptor-interacting protein 1 (CNRIP1).	[10]

References

• [1] Colorectal cancer DNA methylation marker panel validated with high performance in Non-Hodgkin lymphoma.Epigenetics. 2014 Mar;9(3):428-36. doi: 10.4161/epi.27554. Epub 2013 Dec 20.
• [2] Screening of exon methylation biomarkers for colorectal cancer via LC-MS/MS strategy.J Mass Spectrom. 2017 Dec;52(12):860-866. doi: 10.1002/jms.4032.
• [3] A rare genomic duplication in 2p14 underlies autosomal dominant hearing loss DFNA58. Hum Mol Genet. 2020 Jun 3;29(9):1520-1536. doi: 10.1093/hmg/ddaa075.
• [4] Ventral hippocampal overexpression of Cannabinoid Receptor Interacting Protein 1 (CNRIP1) produces a schizophrenia-like phenotype in the rat.Schizophr Res. 2019 Apr;206:263-270. doi: 10.1016/j.schres.2018.11.006. Epub 2018 Dec 3.
• [5] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [6] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [7] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] 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.
• [10] 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.
• [11] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [12] 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.