Details of the Drug

General Information of Drug (ID: DMFOZ60)

Drug Name

aconitine

Synonyms

aconitine; 302-27-2; CHEBI:2430; Acetylbenzoylaconine; NSC56464; 20-ethyl-3alpha,13,15alpha-trihydroxy-1alpha,6alpha,16beta-trimethoxy-4-(methoxymethyl)aconitane-8,14alpha-diyl 8-acetate 14-benzoate; 16-Ethyl-1alpha,6alpha,19beta-trimethoxy-4-(methoxymethyl)-aconitane-3alpha,8,10alpha,11,18alpha-pentol, 8-acetate 10-benzoate; NCGC00163146-01; CAS-302-27-2; DSSTox_RID_81535; DSSTox_CID_26319; SCHEMBL73323; DSSTox_GSID_46319; GTPL2617; DTXSID4046319; CHEMBL1979562; MolPort-002-527-310; Tox21_112015; NSC-56464; AKOS032428256

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]
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Drug Type

Small molecular drug

Structure

3D MOL is unavailable

2D MOL

#Ro5 Violations (Lipinski): 3

Molecular Weight (mw)

645.7

Logarithm of the Partition Coefficient (xlogp)

0.3

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

Chemical Identifiers

Formula: C34H47NO11
IUPAC Name: [(1S,2R,3R,4R,5R,6S,7S,8R,9R,13R,14R,16S,17S,18R)-8-acetyloxy-11-ethyl-5,7,14-trihydroxy-6,16,18-trimethoxy-13-(methoxymethyl)-11-azahexacyclo[7.7.2.12,5.01,10.03,8.013,17]nonadecan-4-yl] benzoate
Canonical SMILES: CCN1C[C@@]2([C@@H](C[C@@H]([C@@]34[C@@H]2[C@H]([C@@H](C31)[C@@]5([C@@H]6[C@H]4C[C@@]([C@@H]6OC(=O)C7=CC=CC=C7)([C@H]([C@@H]5O)OC)O)OC(=O)C)OC)OC)O)COC
InChI: InChI=1S/C34H47NO11/c1-7-35-15-31(16-41-3)20(37)13-21(42-4)33-19-14-32(40)28(45-30(39)18-11-9-8-10-12-18)22(19)34(46-17(2)36,27(38)29(32)44-6)23(26(33)35)24(43-5)25(31)33/h8-12,19-29,37-38,40H,7,13-16H2,1-6H3/t19-,20-,21+,22-,23+,24+,25-,26?,27+,28-,29+,31+,32-,33+,34-/m1/s1
InChIKey: XFSBVAOIAHNAPC-XTHSEXKGSA-N

Cross-matching ID

PubChem CID: 245005
ChEBI ID: CHEBI:2430
CAS Number: 302-27-2
TTD ID: D0A1MW

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Voltage-gated sodium channel alpha Nav1.2 (SCN2A)	TTLJTUF	SCN2A_HUMAN	Activator	[2]
Voltage-gated sodium channel alpha Nav1.5 (SCN5A)	TTZOVE0	SCN5A_HUMAN	Activator	[3]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Drug Response	[4]
Casein kinase II subunit alpha (CSNK2A1)	OT9T8WQM	CSK21_HUMAN	Gene/Protein Processing	[5]
Cyclin-dependent kinase 1 (CDK1)	OTW1SC2N	CDK1_HUMAN	Gene/Protein Processing	[6]
Cytochrome P450 2C8 (CYP2C8)	OTHCWT42	CP2C8_HUMAN	Regulation of Drug Effects	[7]
Cytochrome P450 2C9 (CYP2C9)	OTGLBN29	CP2C9_HUMAN	Regulation of Drug Effects	[7]
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Regulation of Drug Effects	[7]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Gene/Protein Processing	[8]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Regulation of Drug Effects	[7]
Dynamin-1-like protein (DNM1L)	OTXK1Q1G	DNM1L_HUMAN	Post-Translational Modifications	[9]
Dynamin-like 120 kDa protein, mitochondrial (OPA1)	OTJGNWPW	OPA1_HUMAN	Gene/Protein Processing	[9]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

References

1	URL: 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: 2617).
2	Binding of batrachotoxinin A 20-alpha-benzoate to a receptor site associated with sodium channels in synaptic nerve ending particles. J Biol Chem. 1981 Sep 10;256(17):8922-7.
3	Properties of aconitine-modified sodium channels in single cells of mouse ventricular myocardium. Gen Physiol Biophys. 1986 Oct;5(5):473-84.
4	Transcellular transport of aconitine across human intestinal Caco-2 cells. Food Chem Toxicol. 2013 Jul;57:195-200. doi: 10.1016/j.fct.2013.03.033. Epub 2013 Apr 2.
5	Notch1-mediated histone demethylation of HCN4 contributes to aconitine-induced ventricular myocardial dysrhythmia. Toxicol Lett. 2020 Jul 1;327:19-31. doi: 10.1016/j.toxlet.2020.03.017. Epub 2020 Mar 28.
6	Potential Molecular Mechanisms and Drugs for Aconitine-Induced Cardiotoxicity in Zebrafish through RNA Sequencing and Bioinformatics Analysis. Med Sci Monit. 2020 Jun 29;26:e924092. doi: 10.12659/MSM.924092.
7	Involvement of CYP3A4/5 and CYP2D6 in the metabolism of aconitine using human liver microsomes and recombinant CYP450 enzymes. Toxicol Lett. 2011 Apr 10;202(1):47-54. doi: 10.1016/j.toxlet.2011.01.019. Epub 2011 Jan 28.
8	Human PXR-mediated transcriptional activation of CYP3A4 by 'Fuzi' extracts. Toxicol Mech Methods. 2019 Mar;29(3):155-164.
9	Aconitine induces mitochondrial energy metabolism dysfunction through inhibition of AMPK signaling and interference with mitochondrial dynamics in SH-SY5Y cells. Toxicol Lett. 2021 Sep 1;347:36-44. doi: 10.1016/j.toxlet.2021.04.020. Epub 2021 May 1.