KMUP-1   Click here for help

GtoPdb Ligand ID: 8896

Synonyms: KMUP 1
Compound class: Synthetic organic
Comment: KMUP-1 is a novel xanthine-based activator of soluble guanylyl cyclase (sGC) (acts to enhance cGMP levels) reported to be useful clinically for tracheal relaxation [1]. It also has anti-inflammatory actions. Studies in aninals suggest this compound may also be a candidate for clinical investigation as a treatment for pulmonary arterial hypertension [2] or erectile dysfunction [3].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 5
Hydrogen bond donors 0
Rotatable bonds 4
Topological polar surface area 68.3
Molecular weight 402.16
XLogP 3.96
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES Clc1ccccc1N1CCN(CC1)CCn1cnc2c1c(=O)n(C)c(=O)n2C
Isomeric SMILES Clc1ccccc1N1CCN(CC1)CCn1cnc2c1c(=O)n(C)c(=O)n2C
InChI InChI=1S/C19H23ClN6O2/c1-22-17-16(18(27)23(2)19(22)28)26(13-21-17)12-9-24-7-10-25(11-8-24)15-6-4-3-5-14(15)20/h3-6,13H,7-12H2,1-2H3
InChI Key NIDVDYQCGWISJZ-UHFFFAOYSA-N
References
1. Chen I-J, Wu B-N, Yeh J-L. (2008)
Anti-inflammation activity of newly synthesized xanthine derivatives kmup-1 and kmup-3.
Patent number: US20080081816 A1. Assignee: Kaohsiung Medical University. Priority date: 03/10/2006. Publication date: 03/04/2008.
2. Dai ZK, Cheng YJ, Chung HH, Wu JR, Chen IJ, Wu BN. (2010)
KMUP-1 ameliorates monocrotaline-induced pulmonary arterial hypertension through the modulation of Ca2+ sensitization and K+-channel.
Life Sci, 86 (19-20): 747-55. [PMID:20303989]
3. Lin RJ, Wu BN, Lo YC, Shen KP, Lin YT, Huang CH, Chen IJ. (2002)
KMUP-1 relaxes rabbit corpus cavernosum smooth muscle in vitro and in vivo: involvement of cyclic GMP and K(+) channels.
Br J Pharmacol, 135 (5): 1159-66. [PMID:11877322]
4. Liu CM, Lo YC, Wu BN, Wu WJ, Chou YH, Huang CH, An LM, Chen IJ. (2007)
cGMP-enhancing- and alpha1A/alpha1D-adrenoceptor blockade-derived inhibition of Rho-kinase by KMUP-1 provides optimal prostate relaxation and epithelial cell anti-proliferation efficacy.
Prostate, 67 (13): 1397-410. [PMID:17639498]
5. Lo YC, Tseng YT, Liu CM, Wu BN, Wu SN. (2015)
Actions of KMUP-1, a xanthine and piperazine derivative, on voltage-gated Na(+) and Ca(2+) -activated K(+) currents in GH3 pituitary tumour cells.
Br J Pharmacol, 172 (21): 5110-22. [PMID:26276211]
6. Wu BN, Lin RJ, Lin CY, Shen KP, Chiang LC, Chen IJ. (2001)
A xanthine-based KMUP-1 with cyclic GMP enhancing and K(+) channels opening activities in rat aortic smooth muscle.
Br J Pharmacol, 134 (2): 265-74. [PMID:11564644]
7. Wu BN, Lin RJ, Lo YC, Shen KP, Wang CC, Lin YT, Chen IJ. (2004)
KMUP-1, a xanthine derivative, induces relaxation of guinea-pig isolated trachea: the role of the epithelium, cyclic nucleotides and K+ channels.
Br J Pharmacol, 142 (7): 1105-14. [PMID:15237094]