Target Information
| Target General Information | Top | |||||
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| Target ID |
T42724
(Former ID: TTDI03310)
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| Target Name |
Calcium-activated potassium channel KCa3.1 (KCNN4)
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| Synonyms |
SKCa4; SKCa 4; SK4; Putative Gardos channel; KCa4; KCa3.1; Intermediate conductance calcium-activated potassium channel protein 4; IKCa1; IK1
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| Gene Name |
KCNN4
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Alzheimer disease [ICD-11: 8A20] | |||||
| 2 | Chronic pain [ICD-11: MG30] | |||||
| 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.
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| BioChemical Class |
Voltage-gated ion channel
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| UniProt ID | ||||||
| Sequence |
MGGDLVLGLGALRRRKRLLEQEKSLAGWALVLAGTGIGLMVLHAEMLWFGGCSWALYLFL
VKCTISISTFLLLCLIVAFHAKEVQLFMTDNGLRDWRVALTGRQAAQIVLELVVCGLHPA PVRGPPCVQDLGAPLTSPQPWPGFLGQGEALLSLAMLLRLYLVPRAVLLRSGVLLNASYR SIGALNQVRFRHWFVAKLYMNTHPGRLLLGLTLGLWLTTAWVLSVAERQAVNATGHLSDT LWLIPITFLTIGYGDVVPGTMWGKIVCLCTGVMGVCCTALLVAVVARKLEFNKAEKHVHN FMMDIQYTKEMKESAARVLQEAWMFYKHTRRKESHAARRHQRKLLAAINAFRQVRLKHRK LREQVNSMVDISKMHMILYDLQQNLSSSHRALEKQIDTLAGKLDALTELLSTALGPRQLP EPSQQSK Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T54X6V | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | ASP0819 | Drug Info | Phase 2 | Fibromyalgia | [2], [3] | |
| 2 | ICA-17043 | Drug Info | Phase 2 | Alzheimer disease | [2] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Activator | [+] 5 Activator drugs | + | ||||
| 1 | ASP0819 | Drug Info | [4] | |||
| 2 | DC-EBIO | Drug Info | [6] | |||
| 3 | EBIO | Drug Info | [7] | |||
| 4 | SKA-121 | Drug Info | [9] | |||
| 5 | SKA-31 | Drug Info | [10] | |||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | ICA-17043 | Drug Info | [1] | |||
| Blocker (channel blocker) | [+] 2 Blocker (channel blocker) drugs | + | ||||
| 1 | 1-((2-chlorophenyl)diphenylmethyl)-1H-pyrazole | Drug Info | [5] | |||
| 2 | PMID15603962Crac-16 | Drug Info | [8] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| References | Top | |||||
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| REF 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. | |||||
| REF 2 | Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357. | |||||
| REF 3 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 4 | 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. | |||||
| REF 5 | Blockade of the intermediate-conductance calcium-activated potassium channel as a new therapeutic strategy for restenosis. Circulation. 2003 Sep 2;108(9):1119-25. | |||||
| REF 6 | 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. | |||||
| REF 7 | Small conductance calcium-activated potassium channels: from structure to function. Prog Neurobiol. 2010 Jul;91(3):242-55. | |||||
| REF 8 | IKCa-channel blockers. Part 2: discovery of cyclohexadienes. Bioorg Med Chem Lett. 2005 Jan 17;15(2):401-4. | |||||
| REF 9 | New positive Ca2+-activated K+ channel gating modulators with selectivity for KCa3.1. Mol Pharmacol. 2014 Sep;86(3):342-57. | |||||
| REF 10 | 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. | |||||
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