Natural Product (NP) Details

General Information of the NP (ID: NP7145)
Name
Levosimendan
Synonyms
LEVOSIMENDAN; 141505-33-1; Simdax; (-)-OR-1259; UNII-C6T4514L4E; OR-1259; CHEBI:50567; C6T4514L4E; (R)-N-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)carbonohydrazonoyl dicyanide; Levosimedan; DSSTox_CID_26445; DSSTox_RID_81620; DSSTox_GSID_46445; (R)-Simendan; levosimendanum; SMR002529692; Simdax (TN); CAS-141505-33-1; Levosimendan (USAN/INN); Levosimendan [USAN:INN]; OR 1259; OR1259; ((4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl)hydrazono)propanedinitrile; (R)-((4-(1,4,5,6-Tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl)hydrazono) propanedintrile; Mesoxalonitrile (-)-(p((R)-1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl)hydrazone; SCHEMBL83243; MLS003899227; MLS006010741; CHEMBL2051955; DTXSID9046445; Levosimendan, >=98% (HPLC); HMS3264G03; HMS3884N17; KUC109648N; Pharmakon1600-01502356; ACT02710; BCP07048; ZINC3915645; Tox21_112191; Tox21_113768; BDBM50469700; MFCD00867135; NSC759644; s2446; AKOS015895214; Tox21_112191_1; AC-1752; AM84381; CCG-213048; DB00922; DS-8918; NSC 759644; NSC-759644; SB17415; ({4-[(4R)-4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl]phenyl}hydrazono)propanedintrile; KSC-210-010; Mesoxalonitrile (p-((R)-1,4,5,6-tetrahydro-4-methyl-6-oxo-pyridazinyl)phenyl)hydrazone; NCGC00253641-01; NCGC00263564-01; NCGC00263564-02; HY-14286; SW219172-1; A11874; D04720; AB01562970_01; AB01562970_02; 741L087; A807767; Q162541; SR-01000931342; SR-01000931342-2; 1-beta-D-Ribofuranose-1H-1,2,4-triazole-3-methylcarbonate; UNII-349552KRHK component WHXMKTBCFHIYNQ-SECBINFHSA-N; (R)-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)carbonohydrazonoyl dicyanide; 1-cyano-N-{4-[(4R)-4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl]phenyl}methanecarbohydrazonoyl cyanide; 2-[[4-[(4R)-4-methyl-6-oxidanylidene-4,5-dihydro-1H-pyridazin-3-yl]phenyl]hydrazinylidene]propanedinitrile
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Species Origin Homo sapiens ...     Click to Show/Hide
Homo sapiens
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Disease Heart failure [ICD-11: BD10] Approved [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -4.823
 
MDCK Permeability
 -4.871
 
PAMPA
 ++
 
HIA
 - - -
 
Distribution
VDss
 -0.692
 
PPB
 97.7%
 
BBB
 - - -
 
Metabolism
CYP1A2 inhibitor
 ++
CYP1A2 substrate
 - - -
CYP2C19 inhibitor
 +++
CYP2C19 substrate
 - - -
CYP2C9 inhibitor
 +++
CYP2C9 substrate
 - - -
CYP2D6 inhibitor
 - - -
CYP2D6 substrate
 - - -
CYP3A4 inhibitor
 -
CYP3A4 substrate
 +++
CYP2B6 inhibitor
 - - -
CYP2B6 substrate
 - - -
CYP2C8 inhibitor
 +++
HLM Stability
 - - -
 
Excretion
CLplasma
 3.078
 
T1/2
 1.093
Toxicity
DILI
 +++
 
Rat Oral Acute Toxicity
 ++
 
FDAMDD
 +++
 
Respiratory
 +++
 
Human Hepatotoxicity
 -
 
Ototoxicity
 +
 
Drug-induced Nephrotoxicity
 - - -
 
Drug-induced Neurotoxicity
 +++
 
Hematotoxicity
 -
 
Genotoxicity
 +++
 
Tips: 1. For the classification endpoints, the prediction probability values are transformed into six symbols: 0-0.1 (- - -), 0.1-0.3 (- -), 0.3-0.5 (-), 0.5-0.7 (+), 0.7-0.9 (++), and 0.9-1.0 (+++). 2. Additionally, the corresponding relationships of the three labels are as follows: excellent; medium; poor.
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C14H12N6O
PubChem CID
3033825
Canonical SMILES
CC1CC(=O)NN=C1C2=CC=C(C=C2)NN=C(C#N)C#N
InChI
1S/C14H12N6O/c1-9-6-13(21)19-20-14(9)10-2-4-11(5-3-10)17-18-12(7-15)8-16/h2-5,9,17H,6H2,1H3,(H,19,21)/t9-/m1/s1
InChIKey
WHXMKTBCFHIYNQ-SECBINFHSA-N
CAS Number
CAS 141505-33-1
ChEBI ID
CHEBI:50567
TTD Drug ID
D0C4HG
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Adverse Effect can be Decreased by This NP
          Esmolol      Supraventricular tachyarrhythmia     Click to Show/Hide the Molecular Data of This Drug
                 Decreasing Adverse Drug Reaction     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model A case report
                    Experimental
                    Result(s)		 levosimendan in combination with a beta-adrenergic antagonist may have beneficial effects in patients with cardiogenic shock who exhibit tachycardia in response to inotropic agents.
Target and Pathway
Target(s) Troponin C (TNNC1)  Molecule Info  [3]
KEGG Pathway Calcium signaling pathway Click to Show/Hide
2 Cardiac muscle contraction
3 Adrenergic signaling in cardiomyocytes
4 Hypertrophic cardiomyopathy (HCM)
5 Dilated cardiomyopathy
Pathwhiz Pathway Muscle/Heart Contraction Click to Show/Hide
Reactome Striated Muscle Contraction Click to Show/Hide
WikiPathways Striated Muscle Contraction Click to Show/Hide
2 Muscle contraction
References
Reference 1 Emerging drugs for acute and chronic heart failure: current and future developments. Expert Opin Emerg Drugs. 2007 Mar;12(1):75-95.
Reference 2 Treatment of cardiogenic shock with levosimendan in combination with beta-adrenergic antagonists. Br J Anaesth. 2005 Nov;95(5):648-50.
Reference 3 Timing of levosimendan in cardiac surgery. Anadolu Kardiyol Derg. 2009 Jun;9(3):223-30.
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