Target Information
| Target General Infomation | |||||
|---|---|---|---|---|---|
| Target ID |
T67063
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| Former ID |
TTDI01980
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| Target Name |
Maxi K potassium channel
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| Gene Name |
KCNMB4
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| Synonyms |
Calcium activated potassium KCNMA1 (maxiK) channel; KCNMB4
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| Target Type |
Clinical Trial
|
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| Disease | Asthma [ICD10: J45] | ||||
| Cerebrovascular ischaemia [ICD9: 434.91; ICD10: I61-I63] | |||||
| Erectile dysfunction [ICD9: 302.72, 607.84; ICD10: F52.2, N48.4] | |||||
| Function |
Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Increases the apparent Ca(2+)/voltage sensitivity of the KCNMA1 channel. It also modifies KCNMA1 channel kinetics and alters its pharmacological properties. It slows down the activation and the deactivation kinetics of the channel. Acts as a negative regulator of smooth muscle contraction by enhancing the calcium sensitivity to KCNMA1. Its presence is also a requirement for internal binding of the KCNMA1 channel opener dehydrosoyasaponin I (DHS-1) triterpene glycoside and for external binding of the agonist hormone 17-beta-estradiol (E2). Increases the binding activity of charybdotoxin (CTX) toxin to KCNMA1 peptide blocker by increasing the CTX association rate and decreasing the dissociation rate.
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| BioChemical Class |
Calcium-activated potassium channel
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| UniProt ID | |||||
| Sequence |
MAKLRVAYEYTEAEDKSIRLGLFLIISGVVSLFIFGFCWLSPALQDLQATEANCTVLSVQ
QIGEVFECTFTCGADCRGTSQYPCVQVYVNNSESNSRALLHSDEHQLLTNPKCSYIPPCK RENQKNLESVMNWQQYWKDEIGSQPFTCYFNQHQRPDDVLLHRTHDEIVLLHCFLWPLVT FVVGVLIVVLTICAKSLAVKAEAMKKRKFS |
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| Structure |
2K44; 3MT5; 3NAF
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| Drugs and Mode of Action | |||||
| Drug(s) | BMS-223131 | Drug Info | Phase 2 | Erectile dysfunction | [1] |
| CNS-1237 | Drug Info | Terminated | Cerebrovascular ischaemia | [2] | |
| NS-1619 | Drug Info | Terminated | Asthma | [3], [4] | |
| Modulator | BMS-223131 | Drug Info | [1] | ||
| CNS-1237 | Drug Info | [5] | |||
| NS-1619 | Drug Info | ||||
| Inhibitor | iberiotoxin | Drug Info | [6] | ||
| tetraethylammonium | Drug Info | [6] | |||
| Blocker (channel blocker) | paxilline | Drug Info | [7] | ||
| slotoxin | Drug Info | [8] | |||
| Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
| TEP | EXP Info | ||||
| Pathways | |||||
| KEGG Pathway | cGMP-PKG signaling pathway | ||||
| Vascular smooth muscle contraction | |||||
| Insulin secretion | |||||
| Salivary secretion | |||||
| Pancreatic secretion | |||||
| Reactome | cGMP effects | ||||
| WikiPathways | Potassium Channels | ||||
| Platelet homeostasis | |||||
| References | |||||
| REF 1 | Effect of 4-(5-chloro-2-hydroxyphenyl)-3-(2-hydroxyethyl)-6-(trifluoromethyl)-quinolin-2(1H)-one (BMS-223131), a novel opener of large conductance Ca2+-activated K+ (maxi-K) channels on normal and stress-aggravated colonic motility and visceral nociception. J Pharmacol Exp Ther. 2005 May;313(2):840-7. Epub 2005 Feb 8. | ||||
| REF 2 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001959) | ||||
| REF 3 | (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. (Ligand id: 4272). | ||||
| REF 4 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001878) | ||||
| REF 5 | Effects of Ca2+ and Na+ channel inhibitors in vitro and in global cerebral ischaemia in vivo. Eur J Pharmacol. 1997 Aug 6;332(2):121-31. | ||||
| REF 6 | (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: 380). | ||||
| REF 7 | Paxilline inhibition of the alpha-subunit of the high-conductance calcium-activated potassium channel. Neuropharmacology. 1996;35(7):963-8. | ||||
| REF 8 | Slotoxin, alphaKTx1.11, a new scorpion peptide blocker of MaxiK channels that differentiates between alpha and alpha+beta (beta1 or beta4) complexes. FEBS Lett. 2001 Sep 21;505(3):369-73. | ||||
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