Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT32NQ1)

• DTT Name: Short transient receptor potential channel 5 (TRPC5)
• Synonyms: hTRP5; hTRP-5; TrpC5; Transient receptor protein 5; TRP-5
• Gene Name: TRPC5
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Transient receptor potential catioin channel
• UniProt ID: TRPC5_HUMAN
• TTD ID: T00156
• Sequence:
  MAQLYYKKVNYSPYRDRIPLQIVRAETELSAEEKAFLNAVEKGDYATVKQALQEAEIYYN
  VNINCMDPLGRSALLIAIENENLEIMELLLNHSVYVGDALLYAIRKEVVGAVELLLSYRR
  PSGEKQVPTLMMDTQFSEFTPDITPIMLAAHTNNYEIIKLLVQKRVTIPRPHQIRCNCVE
  CVSSSEVDSLRHSRSRLNIYKALASPSLIALSSEDPILTAFRLGWELKELSKVENEFKAE
  YEELSQQCKLFAKDLLDQARSSRELEIILNHRDDHSEELDPQKYHDLAKLKVAIKYHQKE
  FVAQPNCQQLLATLWYDGFPGWRRKHWVVKLLTCMTIGFLFPMLSIAYLISPRSNLGLFI
  KKPFIKFICHTASYLTFLFMLLLASQHIVRTDLHVQGPPPTVVEWMILPWVLGFIWGEIK
  EMWDGGFTEYIHDWWNLMDFAMNSLYLATISLKIVAYVKYNGSRPREEWEMWHPTLIAEA
  LFAISNILSSLRLISLFTANSHLGPLQISLGRMLLDILKFLFIYCLVLLAFANGLNQLYF
  YYETRAIDEPNNCKGIRCEKQNNAFSTLFETLQSLFWSVFGLLNLYVTNVKARHEFTEFV
  GATMFGTYNVISLVVLLNMLIAMMNNSYQLIADHADIEWKFARTKLWMSYFDEGGTLPPP
  FNIIPSPKSFLYLGNWFNNTFCPKRDPDGRRRRRNLRSFTERNADSLIQNQHYQEVIRNL
  VKRYVAAMIRNSKTHEGLTEENFKELKQDISSFRYEVLDLLGNRKHPRSFSTSSTELSQR
  DDNNDGSGGARAKSKSVSFNLGCKKKTCHGPPLIRTMPRSSGAQGKSKAESSSKRSFMGP
  SLKKLGLLFSKFNGHMSEPSSEPMYTISDGIVQQHCMWQDIRYSQMEKGKAEACSQSEIN
  LSEVELGEVQGAAQSSECPLACSSSLHCASSICSSNSKLLDSSEDVFETWGEACDLLMHK
  WGDGQEEQVTTRL
• 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. Has also been shown to be calcium-selective. 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

2 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]
GFB-887	DM2IJWG	Diabetic nephropathy	GB61.Z	Phase 2	[3]

8 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(-)-englerin A	DMPQBWY	Discovery agent	N.A.	Investigative	[4]
2-APB	DM9AKVR	Discovery agent	N.A.	Investigative	[5]
bromoenol lactone	DMKQ0CA	Discovery agent	N.A.	Investigative	[6]
BTP2	DMNM63G	Discovery agent	N.A.	Investigative	[7]
daidzein	DMRFTJX	Discovery agent	N.A.	Investigative	[7]
KB-R7943	DMMD5W3	Discovery agent	N.A.	Investigative	[8]
lysophosphatidylcholine	DMOGFVH	Discovery agent	N.A.	Investigative	[7]
ML204	DM15YL0	Discovery agent	N.A.	Investigative	[9]

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] Safety and Efficacy of GFB-887, a TRPC5 Channel Inhibitor, in Patients With Focal Segmental Glomerulosclerosis, Treatment-Resistant Minimal Change Disease, or Diabetic Nephropathy: TRACTION-2 Trial Design. Kidney Int Rep. 2021 Jul 23;6(10):2575-2584.
• [4] (-)-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.
• [5] Block of TRPC5 channels by 2-aminoethoxydiphenyl borate: a differential, extracellular and voltage-dependent effect. Br J Pharmacol. 2005 Jun;145(4):405-14.
• [6] Bromoenol lactone inhibits voltage-gated Ca2+ and transient receptor potential canonical channels. J Pharmacol Exp Ther. 2011 Nov;339(2):329-40.
• [7] 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: 490).
• [8] The Na+/Ca2+ exchange inhibitor KB-R7943 potently blocks TRPC channels. Biochem Biophys Res Commun. 2007 Sep 14;361(1):230-6.
• [9] 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.