Natural Product (NP) Details

General Information of the NP (ID: NP3874)
Name
Physostigmine
Synonyms
physostigmine; Eserine; 57-47-6; Antilirium; Physostol; Esromiotin; Ezerin; Calabarine; Erserine; Fysostigmin; (3aS,8aR)-1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl methylcarbamate; (-)-physostigmine; Eserolein, methylcarbamate (ester); UNII-9U1VM840SP; CHEMBL94; 57-47-6 (free base); [(3aR,8bS)-3,4,8b-trimethyl-2,3a-dihydro-1H-pyrrolo[2,3-b]indol-7-yl] N-methylcarbamate; 9U1VM840SP; CHEBI:27953; NSC30782; NSC-30782; NCGC00093889-03; DSSTox_CID_3471; DSSTox_RID_77040; DSSTox_GSID_23471; Fysostigmin [Czech]; CHEMBL537674; Pyrrolo(2,3-b)indol-5-ol, 1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethyl-, methylcarbamate (ester), (3aS-cis)-; CAS-57-47-6; CCRIS 3422; HSDB 3161; MCV 4484; EINECS 200-332-8; Eserolein, methylcarbamate; NIH 10421; NSC 30782; Physostigmine [USP:BAN]; RCRA waste no. P204; physostigmin; CS 58525; Methyl-carbamic acid, ester with eseroline; Carbamic acid, methyl-, ester with eseroline; (-) physostigmine; Eserine (TN); Physostigmine (USP); Physostigmine free base; Spectrum_000916; Spectrum_001789; SpecPlus_000381; Prestwick0_000566; Prestwick1_000566; Prestwick2_000566; Prestwick3_000566; Spectrum2_000330; Spectrum2_000757; Spectrum2_001283; Spectrum3_000545; Spectrum3_000901; Spectrum4_000997; Spectrum4_001631; Spectrum4_001913; Spectrum5_000441; Spectrum5_000626; Spectrum5_001672; physostigmine.salicylic acid; 1,2,3,3abeta,8abeta-Hexahydro-1,3a,8-trimethylpyrrolo(2,3-b)-indol-5-yl methylcarbamate; Lopac0_000483; SCHEMBL24044; BSPBio_000352; BSPBio_002189; KBioGR_001433; KBioGR_002061; KBioGR_002533; KBioSS_001396; KBioSS_002279; (3aS-cis)-1,2,3,3a,8,8a-Hexahydro-1,3a,8-trimethylpyrrolo(2,3-b)indol-5-ol methylcarbamate (ester); MLS001304022; DivK1c_006477; SPECTRUM1500753; SPBio_000339; SPBio_000774; SPBio_001285; SPBio_002571; BPBio1_000388; cid_657348; GTPL6598; MEGxp0_001872; DTXSID3023471; ACon1_000097; BDBM11023; KBio1_001421; KBio2_001396; KBio2_002278; KBio2_003964; KBio2_004846; KBio2_006532; KBio2_007414; KBio3_001689; KBio3_001842; Eserine, >=98.0% (N); HMS1921G06; HMS2089M11; HMS2236L08; HMS3261B07; BCP19735; Carbamic acid, ester with eseroline; HY-N6608; MCV-4484; Pyrrolo(2,3-b)indol-5-ol, 1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethyl-, 5-(N-methylcarbamate), (3aS,8aR)-; Tox21_111228; Tox21_301591; Tox21_500483; BDBM50004000; BDBM50222010; CCG-38605; MFCD00151090; ZINC91689892; AKOS016843649; Tox21_111228_1; DB00981; LP00483; MCULE-2638001883; MCULE-9310809074; SDCCGMLS-0066585.P001; SDCCGSBI-0050467.P005; NCGC00093889-01; NCGC00093889-02; NCGC00093889-04; NCGC00093889-05; NCGC00093889-06; NCGC00093889-07; NCGC00093889-08; NCGC00093889-09; NCGC00093889-10; NCGC00093889-12; NCGC00093889-13; NCGC00093889-20; NCGC00255345-01; NCGC00261168-01; AC-15983; Pyrrolo(2,3-b)indol-5-ol, 1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethyl-, methylcarbamate (ester), (3aS,8aR)-; Pyrrolo(2,3-b)indol-5-ol, 1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethyl-, methylcarbamate (ester), (3aS-cis); SMR000718753; SBI-0050467.P004; CS-0034353; EU-0100483; P0406; Physostigmine 100 microg/mL in Acetonitrile; C06535; D00196; E 8375; Q410595; Eserine; Antilirium; Physostol; Esromiotin; Ezerin; SR-01000075341-1; WLN: T B556 EN GNTT&J B1 E1 G1 KOVM1; BRD-K25650355-001-02-5; BRD-K25650355-059-02-3; BRD-K25650355-059-12-2; (3aS,8aR)-1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl methylcarbamate hydrochloride; (3aS,8aR)-1,3a,8-trimethyl-1H,2H,3H,3aH,8H,8aH-pyrrolo[2,3-b]indol-5-yl N-methylcarbamate; (3aS,8aR)-1,3a,8-trimethyl-1H,2H,3H,3aH,8H,8aH-pyrrolo[2,3-b]indol-5-yl N-methylcarbamate; 2-hydroxybenzoic acid; Pyrrolo[2, 1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethyl-, methylcarbamate (ester), (3aS-cis)-
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Species Origin Physostigma venenosum ...     Click to Show/Hide
Physostigma venenosum
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Fabales
Family: Fabaceae
Genus: Physostigma
Species: Physostigma venenosum
Disease Lips/oral mucosa miscellaneous disorder [ICD-11: DA02] Discontinued in Phase 2 [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -5.115
 
MDCK Permeability
 -4.848
 
PAMPA
 -
 
HIA
 ++
 
Distribution
VDss
 0.651
 
PPB
 39.1%
 
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
 11.059
 
T1/2
 1.4
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
C15H21N3O2
PubChem CID
5983
Canonical SMILES
CC12CCN(C1N(C3=C2C=C(C=C3)OC(=O)NC)C)C
InChI
1S/C15H21N3O2/c1-15-7-8-17(3)13(15)18(4)12-6-5-10(9-11(12)15)20-14(19)16-2/h5-6,9,13H,7-8H2,1-4H3,(H,16,19)/t13-,15+/m1/s1
InChIKey
PIJVFDBKTWXHHD-HIFRSBDPSA-N
CAS Number
CAS 57-47-6
ChEBI ID
CHEBI:27953
Herb ID
HBIN039772
SymMap ID
SMIT19436
TTD Drug ID
D09JVV
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Deprenyl      Parkinson's disease     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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
                    Experimental
                    Result(s)		 Based on earlier positive findings in Alzheimer patients with the monoamine oxidase B inhibitor, 1-deprenyl, the authors speculate that a combination of physostigmine, the short-acting cholinesterase inhibitor, and 1-deprenyl might be more beneficial than either agent alone.
Target and Pathway
Target(s) Acetylcholinesterase (AChE)  Molecule Info  [3]
KEGG Pathway Glycerophospholipid metabolism Click to Show/Hide
2 Cholinergic synapse
Panther Pathway Muscarinic acetylcholine receptor 1 and 3 signaling pathway Click to Show/Hide
2 Muscarinic acetylcholine receptor 2 and 4 signaling pathway
3 Nicotinic acetylcholine receptor signaling pathway
Pathwhiz Pathway Phospholipid Biosynthesis Click to Show/Hide
Pathway Interaction Database ATF-2 transcription factor network Click to Show/Hide
WikiPathways Monoamine Transport Click to Show/Hide
2 Biogenic Amine Synthesis
3 Acetylcholine Synthesis
4 Integrated Pancreatic Cancer Pathway
References
Reference 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: 6598).
Reference 2 A strategy of "combination chemotherapy" in Alzheimer's disease: rationale and preliminary results with physostigmine plus deprenyl. Int Psychogeriatr. 1992;4 Suppl 2:291-309.
Reference 3 The effects of physostigmine on acetylcholinesterase activity of CSF plasma and brain. A comparison of intravenous and intraventricular administration in beagle dogs. Neuropharmacology. 1986 Oct;25(10):1167-77.
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