Details of Drug Off-Target (DOT)

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

• DOT Name: Short transient receptor potential channel 1 (TRPC1)
• Synonyms: TrpC1; Transient receptor protein 1; TRP-1
• Gene Name: TRPC1
• UniProt ID: TRPC1_HUMAN
• Pfam ID: PF00520 ; PF08344
• Sequence:
  MMAALYPSTDLSGASSSSLPSSPSSSSPNEVMALKDVREVKEENTLNEKLFLLACDKGDY
  YMVKKILEENSSGDLNINCVDVLGRNAVTITIENENLDILQLLLDYGCQSADALLVAIDS
  EVVGAVDILLNHRPKRSSRPTIVKLMERIQNPEYSTTMDVAPVILAAHRNNYEILTMLLK
  QDVSLPKPHAVGCECTLCSAKNKKDSLRHSRFRLDIYRCLASPALIMLTEEDPILRAFEL
  SADLKELSLVEVEFRNDYEELARQCKMFAKDLLAQARNSRELEVILNHTSSDEPLDKRGL
  LEERMNLSRLKLAIKYNQKEFVSQSNCQQFLNTVWFGQMSGYRRKPTCKKIMTVLTVGIF
  WPVLSLCYLIAPKSQFGRIIHTPFMKFIIHGASYFTFLLLLNLYSLVYNEDKKNTMGPAL
  ERIDYLLILWIIGMIWSDIKRLWYEGLEDFLEESRNQLSFVMNSLYLATFALKVVAHNKF
  HDFADRKDWDAFHPTLVAEGLFAFANVLSYLRLFFMYTTSSILGPLQISMGQMLQDFGKF
  LGMFLLVLFSFTIGLTQLYDKGYTSKEQKDCVGIFCEQQSNDTFHSFIGTCFALFWYIFS
  LAHVAIFVTRFSYGEELQSFVGAVIVGTYNVVVVIVLTKLLVAMLHKSFQLIANHEDKEW
  KFARAKLWLSYFDDKCTLPPPFNIIPSPKTICYMISSLSKWICSHTSKGKVKRQNSLKEW
  RNLKQKRDENYQKVMCCLVHRYLTSMRQKMQSTDQATVENLNELRQDLSKFRNEIRDLLG
  FRTSKYAMFYPRN
• Function: Thought to form a receptor-activated non-selective calcium permeant cation channel. Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Seems to be also activated by intracellular calcium store depletion.
• Tissue Specificity: Seems to be ubiquitous.
• KEGG Pathway:
  Axon guidance (hsa04360)
  Glutamatergic sy.pse (hsa04724)
  Serotonergic sy.pse (hsa04726)
  GnRH secretion (hsa04929)
  Pancreatic secretion (hsa04972)
• Reactome Pathway:
  Role of second messengers in netrin-1 signaling (R-HSA-418890)
  Ion homeostasis (R-HSA-5578775)
  Antigen activates B Cell Receptor (BCR) leading to generation of second messengers (R-HSA-983695)
  TRP channels (R-HSA-3295583)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Short transient receptor potential channel 1 (TRPC1) affects the response to substance of Doxorubicin.	[6]
Marinol	DM70IK5	Approved	Short transient receptor potential channel 1 (TRPC1) increases the response to substance of Marinol.	[7]
Topotecan	DMP6G8T	Approved	Short transient receptor potential channel 1 (TRPC1) affects the response to substance of Topotecan.	[6]

5 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 Short transient receptor potential channel 1 (TRPC1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Short transient receptor potential channel 1 (TRPC1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Short transient receptor potential channel 1 (TRPC1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Short transient receptor potential channel 1 (TRPC1).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Short transient receptor potential channel 1 (TRPC1).	[5]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [6] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
• [7] Induction of intracellular calcium elevation by Delta9-tetrahydrocannabinol in T cells involves TRPC1 channels. J Leukoc Biol. 2006 Jan;79(1):202-13. doi: 10.1189/jlb.0505274. Epub 2005 Oct 21.