Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTX0H5W)

• DTT Name: Short transient receptor potential channel 4 (TRPC4)
• Synonyms: hTrp4; hTrp-4; TrpC4; Trp-related protein 4
• Gene Name: TRPC4
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Transient receptor potential catioin channel
• UniProt ID: TRPC4_HUMAN
• TTD ID: T91558
• Sequence:
  MAQFYYKRNVNAPYRDRIPLRIVRAESELSPSEKAYLNAVEKGDYASVKKSLEEAEIYFK
  ININCIDPLGRTALLIAIENENLELIELLLSFNVYVGDALLHAIRKEVVGAVELLLNHKK
  PSGEKQVPPILLDKQFSEFTPDITPIILAAHTNNYEIIKLLVQKGVSVPRPHEVRCNCVE
  CVSSSDVDSLRHSRSRLNIYKALASPSLIALSSEDPFLTAFQLSWELQELSKVENEFKSE
  YEELSRQCKQFAKDLLDQTRSSRELEIILNYRDDNSLIEEQSGNDLARLKLAIKYRQKEF
  VAQPNCQQLLASRWYDEFPGWRRRHWAVKMVTCFIIGLLFPVFSVCYLIAPKSPLGLFIR
  KPFIKFICHTASYLTFLFLLLLASQHIDRSDLNRQGPPPTIVEWMILPWVLGFIWGEIKQ
  MWDGGLQDYIHDWWNLMDFVMNSLYLATISLKIVAFVKYSALNPRESWDMWHPTLVAEAL
  FAIANIFSSLRLISLFTANSHLGPLQISLGRMLLDILKFLFIYCLVLLAFANGLNQLYFY
  YEETKGLTCKGIRCEKQNNAFSTLFETLQSLFWSIFGLINLYVTNVKAQHEFTEFVGATM
  FGTYNVISLVVLLNMLIAMMNNSYQLIADHADIEWKFARTKLWMSYFEEGGTLPTPFNVI
  PSPKSLWYLIKWIWTHLCKKKMRRKPESFGTIGRRAADNLRRHHQYQEVMRNLVKRYVAA
  MIRDAKTEEGLTEENFKELKQDISSFRFEVLGLLRGSKLSTIQSANASKESSNSADSDEK
  SDSEGNSKDKKKNFSLFDLTTLIHPRSAAIASERHNISNGSALVVQEPPREKQRKVNFVT
  DIKNFGLFHRRSKQNAAEQNANQIFSVSEEVARQQAAGPLERNIQLESRGLASRGDLSIP
  GLSEQCVLVDHRERNTDTLGLQVGKRVCPFKSEKVVVEDTVPIIPKEKHAKEEDSSIDYD
  LNLPDTVTHEDYVTTRL
• Function: Form a receptor-activated non-selective calcium permeant cation channel. Acts as a cell-cell contact-dependent endothelial calcium entry channel. Probably operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Mediates cation entry, with an enhanced permeability to barium over calcium. May also be activated by intracellular calcium store depletion.
• KEGG Pathway:
  Axon guidance (hsa04360)
  GnRH secretion (hsa04929)
• Reactome Pathway:
  Role of second messengers in netrin-1 signaling (R-HSA-418890)
  TRP channels (R-HSA-3295583)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BI 1358894	DM740BS	Depression	6A70-6A7Z	Phase 2	[2]

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(-)-englerin A	DMPQBWY	Discovery agent	N.A.	Investigative	[3]
2-APB	DM9AKVR	Discovery agent	N.A.	Investigative	[4]
ML204	DM15YL0	Discovery agent	N.A.	Investigative	[5]

References

• [1] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [2] Clinical pipeline report, company report or official report of Boehringer Ingelheim.
• [3] (-)-Englerin is a potent and selective activator of TRPC4 and TRPC5 calcium channels. Angew Chem Int Ed Engl. 2015 Mar 16;54(12):3787-91.
• [4] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 489).
• [5] Identification of ML204, a novel potent antagonist that selectively modulates native TRPC4/C5 ion channels. J Biol Chem. 2011 Sep 23;286(38):33436-46.