Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT2T5M0)

• DTT Name: Calcium-activated potassium channel KCa2.2 (KCNN2)
• Synonyms: Small conductance calcium-activated potassium channel protein 2; SKCa2; SKCa 2; SK2; KCa2.2
• Gene Name: KCNN2
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Voltage-gated ion channel
• UniProt ID: KCNN2_HUMAN
• TTD ID: T86271
• Sequence:
  MSSCRYNGGVMRPLSNLSASRRNLHEMDSEAQPLQPPASVGGGGGASSPSAAAAAAAAVS
  SSAPEIVVSKPEHNNSNNLALYGTGGGGSTGGGGGGGGSGHGSSSGTKSSKKKNQNIGYK
  LGHRRALFEKRKRLSDYALIFGMFGIVVMVIETELSWGAYDKASLYSLALKCLISLSTII
  LLGLIIVYHAREIQLFMVDNGADDWRIAMTYERIFFICLEILVCAIHPIPGNYTFTWTAR
  LAFSYAPSTTTADVDIILSIPMFLRLYLIARVMLLHSKLFTDASSRSIGALNKINFNTRF
  VMKTLMTICPGTVLLVFSISLWIIAAWTVRACERYHDQQDVTSNFLGAMWLISITFLSIG
  YGDMVPNTYCGKGVCLLTGIMGAGCTALVVAVVARKLELTKAEKHVHNFMMDTQLTKRVK
  NAAANVLRETWLIYKNTKLVKKIDHAKVRKHQRKFLQAIHQLRSVKMEQRKLNDQANTLV
  DLAKTQNIMYDMISDLNERSEDFEKRIVTLETKLETLIGSIHALPGLISQTIRQQQRDFI
  EAQMESYDKHVTYNAERSRSSSRRRRSSSTAPPTSSESS
• Function: Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin.
• KEGG Pathway:
  Serotonergic synapse (hsa04726)
  Insulin secretion (hsa04911)
  GnRH secretion (hsa04929)
  Bile secretion (hsa04976)
• Reactome Pathway:
  Acetylcholine inhibits contraction of outer hair cells (R-HSA-9667769)
  Ca2+ activated K+ channels (R-HSA-1296052)

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
dequalinium	DMXM19W	Myelopathy	8B42	Clinical trial	[1]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
zoxazolamine	DM70TKB	Multiple myeloma	2A83	Terminated	[2]

7 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
apamin	DMYNBK5	Discovery agent	N.A.	Investigative	[3]
CyPPA	DM64L9I	Discovery agent	N.A.	Investigative	[4]
DC-EBIO	DM2T5OV	Discovery agent	N.A.	Investigative	[5]
EBIO	DMPKI0N	Discovery agent	N.A.	Investigative	[6]
UCL1684	DMZNJFU	Discovery agent	N.A.	Investigative	[7]
UCL1848	DM2CN0A	Discovery agent	N.A.	Investigative	[8]
[14C]TEA	DM6SFYH	Discovery agent	N.A.	Investigative	[6]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Multiple myeloma	2C82	Bone marrow	5.17E-02	1.41E-02	0.15

References

• [1] Block of rat brain recombinant SK channels by tricyclic antidepressants and related compounds. Eur J Pharmacol. 2000 Jul 28;401(1):1-7.
• [2] Modulation of recombinant small-conductance Ca(2+)-activated K(+) channels by the muscle relaxant chlorzoxazone and structurally related compounds. J Pharmacol Exp Ther. 2001 Mar;296(3):683-9.
• [3] SK2 encodes the apamin-sensitive Ca(2+)-activated K(+) channels in the human leukemic T cell line, Jurkat. FEBS Lett. 2000 Mar 10;469(2-3):196-202.
• [4] Selective positive modulation of the SK3 and SK2 subtypes of small conductance Ca2+-activated K+ channels. Br J Pharmacol. 2007 Jul;151(5):655-65.
• [5] Specific enhancement of SK channel activity selectively potentiates the afterhyperpolarizing current I(AHP) and modulates the firing properties of ... J Biol Chem. 2005 Dec 16;280(50):41404-11.
• [6] Small conductance calcium-activated potassium channels: from structure to function. Prog Neurobiol. 2010 Jul;91(3):242-55.
• [7] Pharmacological characterization of small-conductance Ca(2+)-activated K(+) channels stably expressed in HEK 293 cells. Br J Pharmacol. 2000 Mar;129(5):991-9.
• [8] Calcium-activated potassium channels sustain calcium signaling in T lymphocytes. Selective blockers and manipulated channel expression levels. J Biol Chem. 2001 Apr 13;276(15):12249-56.