Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT7M9I6)

• DTT Name: Calcium-activated potassium channel KCa3.1 (KCNN4)
• Synonyms: SKCa4; SKCa 4; SK4; Putative Gardos channel; KCa4; KCa3.1; Intermediate conductance calcium-activated potassium channel protein 4; IKCa1; IK1
• Gene Name: KCNN4
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Voltage-gated ion channel
• UniProt ID: KCNN4_HUMAN
• TTD ID: T42724
• Sequence:
  MGGDLVLGLGALRRRKRLLEQEKSLAGWALVLAGTGIGLMVLHAEMLWFGGCSWALYLFL
  VKCTISISTFLLLCLIVAFHAKEVQLFMTDNGLRDWRVALTGRQAAQIVLELVVCGLHPA
  PVRGPPCVQDLGAPLTSPQPWPGFLGQGEALLSLAMLLRLYLVPRAVLLRSGVLLNASYR
  SIGALNQVRFRHWFVAKLYMNTHPGRLLLGLTLGLWLTTAWVLSVAERQAVNATGHLSDT
  LWLIPITFLTIGYGDVVPGTMWGKIVCLCTGVMGVCCTALLVAVVARKLEFNKAEKHVHN
  FMMDIQYTKEMKESAARVLQEAWMFYKHTRRKESHAARRHQRKLLAAINAFRQVRLKHRK
  LREQVNSMVDISKMHMILYDLQQNLSSSHRALEKQIDTLAGKLDALTELLSTALGPRQLP
  EPSQQSK
• Function: Activation is followed by membrane hyperpolarization which promotes calcium influx. Required for maximal calcium influx and proliferation during the reactivation of naive T-cells. Plays a role in the late stages of EGF-induced macropinocytosis. Forms a voltage-independent potassium channel that is activated by intracellular calcium.
• KEGG Pathway:
  Insulin secretion (hsa04911)
  GnRH secretion (hsa04929)
  Salivary secretion (hsa04970)
  Protein digestion and absorption (hsa04974)
• Reactome Pathway: Ca2+ activated K+ channels (R-HSA-1296052)

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
ASP0819	DM6HJ3V	Fibromyalgia	MG30.01	Phase 2	[2]
ICA-17043	DMRFY7I	Alzheimer disease	8A20	Phase 2	[1]

6 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1-((2-chlorophenyl)diphenylmethyl)-1H-pyrazole	DMQEJVU	Conjunctival fibrosis	9A61.3	Investigative	[3]
DC-EBIO	DM2T5OV	Discovery agent	N.A.	Investigative	[4]
EBIO	DMPKI0N	Discovery agent	N.A.	Investigative	[5]
PMID15603962Crac-16	DMN5LZQ	Discovery agent	N.A.	Investigative	[6]
SKA-121	DMBL7YN	Discovery agent	N.A.	Investigative	[7]
SKA-31	DMX34F1	Discovery agent	N.A.	Investigative	[8]

References

• [1] Senicapoc (ICA-17043): a potential therapy for the prevention and treatment of hemolysis-associated complications in sickle cell anemia.Expert Opin Investig Drugs.2009 Feb;18(2):231-9.
• [2] Efficacy and Safety of ASP0819 in Patients with Fibromyalgia: Results of a Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial. J Pain Res. 2020 Dec 10;13:3355-3369.
• [3] Blockade of the intermediate-conductance calcium-activated potassium channel as a new therapeutic strategy for restenosis. Circulation. 2003 Sep 2;108(9):1119-25.
• [4] Benzimidazolone activators of chloride secretion: potential therapeutics for cystic fibrosis and chronic obstructive pulmonary disease. J Pharmacol Exp Ther. 2001 Feb;296(2):600-11.
• [5] Small conductance calcium-activated potassium channels: from structure to function. Prog Neurobiol. 2010 Jul;91(3):242-55.
• [6] IKCa-channel blockers. Part 2: discovery of cyclohexadienes. Bioorg Med Chem Lett. 2005 Jan 17;15(2):401-4.
• [7] New positive Ca2+-activated K+ channel gating modulators with selectivity for KCa3.1. Mol Pharmacol. 2014 Sep;86(3):342-57.
• [8] Naphtho[1,2-d]thiazol-2-ylamine (SKA-31), a new activator of KCa2 and KCa3.1 potassium channels, potentiates the endothelium-derived hyperpolarizing factor response and lowers blood pressure. Mol Pharmacol. 2009 Feb;75(2):281-95.