Natural Product: NPC329793

Natural Product IDNPC329793
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Ibogaine
IUPAC Name n.a.
Synonyms 10-Methoxyibogamine; Ibogaine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL222287
PubChem CID 442108
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0002748] Ibogan-type alkaloids

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey HSIBGVUMFOSJPD-NXWOVTFFSA-N
Standard InCHI InChI=1S/C20H26N2O/c1-3-13-8-12-9-17-19-15(6-7-22(11-12)20(13)17)16-10-14(23-2)4-5-18(16)21-19/h4-5,10,12-13,17,20-21H,3,6-9,11H2,1-2H3/t12-,13-,17-,20-/m0/s1
SMILES CCC1CC2CC3C1N(C2)CCC4=C3NC5=C4C=C(C=C5)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   310.2 Volume:   331.932
?
Van der Waals volume.
Dense:   0.935 LogP:   3.551
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.247
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.701
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   23.0
TPSA:   28.26
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   6.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.91 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.905 Fsp3:   0.6
MCE-18:   89.062
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.517 Fluc inhibitor:   0.027
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.917
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.381
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.023

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.843 MDCK Permeability:   -4.928
Pgp-inhibitor:   0.171 Pgp-substrate:   0.14
PAMPA:   0.0
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.001
20% Bioavailability (F20%):   0.108 30% Bioavailability (F30%):   0.212
50% Bioavailability (F50%):   0.859

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.947 MRP1:   0.997
Plasma Protein Binding (PPB):   84.335% Volume Distribution (VD):   0.585
Fu: 13.074%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.056
OATP1B3 inhibitor:   0.654 BCRP inhibitor:   0.954
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.002
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.031
CYP2C9-inhibitor:   0.613 CYP2C9-substrate:   0.994
CYP2D6-inhibitor:   0.982 CYP2D6-substrate:   0.527
CYP3A4-inhibitor:   0.131 CYP3A4-substrate:   0.15
CYP2B6-substrate:   0.999 CYP2C8-inhibitor:   0.005
HLM stability:   0.985
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  9.57 Half-life (T1/2):  0.793

ADMET: Toxicity

hERG Blockers:  0.754 hERG Blockers (10um):  0.845
Human Hepatotoxicity (H-HT):  0.643 Drug-induced Liver Injury (DILI):  0.483
AMES Toxicity:  0.595 Rat Oral Acute Toxicity:  0.747
Maximum Recommended Daily Dose:  0.969 Skin Sensitization:  0.056
Carcinogencity:  0.684 Eye Corrosion:  0.0
Eye Irritation:  0.012 Respiratory Toxicity:  0.983
Drug-induced Neurotoxicity:  0.873 Ototoxicity:  0.935
Hematotoxicity:  0.186 Drug-induced Nephrotoxicity:  0.523
Genotoxicity:  0.309 RPMI-8226 Immunitoxicity:  0.09
A549 Cytotoxicity:  0.461 Hek293 Cytotoxicity:  0.876
BCF:   2.305
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   4.392
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.651
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.206
?
96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO32495 tabernaemontana calcarea Species Apocynaceae Eukaryota n.a. Madagascar rainforest n.a. PMID[12713407]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



  NP Quantity Composition/Concentration

Organism ID Organism Name Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



 Biological Activity

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1073 Individual protein Dopamine transporter Rattus norvegicus IC50 = 4110.0 nM PMID[19674906]
NPT1072 Individual protein Serotonin transporter Rattus norvegicus IC50 = 590.0 nM PMID[12444691]
NPT1857 Individual protein Dopamine D1 receptor Rattus norvegicus IC50 > 10000.0 nM PMID[12444691]
NPT1858 Individual protein Dopamine D2 receptor Rattus norvegicus IC50 > 10000.0 nM PubChem BioAssay data set
NPT3056 Individual protein Dopamine D3 receptor Rattus norvegicus IC50 > 10000.0 nM PMID[15165132]
NPT1069 Individual protein Mu opioid receptor Rattus norvegicus IC50 = 3760.0 nM DrugMatrix in vivo data: Pathology
NPT1070 Individual protein Sigma-1 receptor Cavia porcellus Ki = 250.0 nM Open TG-GATES in vivo data: Hematology
NPT1072 Individual protein Serotonin transporter Rattus norvegicus IC50 = 6300.0 nM PMID[18443122]
NPT1072 Individual protein Serotonin transporter Rattus norvegicus IC50 = 2500.0 nM PMID[18443122]
NPT295 Individual protein Serotonin transporter Homo sapiens Kinact = 2.26 nM PMID[17698848]
NPT296 Individual protein Sigma opioid receptor Homo sapiens Ki = 8554.0 nM PMID[20521771]
NPT3601 Individual protein Kappa opioid receptor Rattus norvegicus IC50 = 25000.0 nM DrugMatrix in vivo data: Pathology
NPT1496 Protein complex Glutamate NMDA receptor Rattus norvegicus IC50 = 5200.0 nM DrugMatrix in vivo data: Pathology

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT179 Cell line A2780 Homo sapiens IC50 = 10.2 ug.mL-1 PMID[10924166]
NPT2 Others Unspecified n.a. Ki = 9310.0 nM PMID[19012394]
NPT2 Others Unspecified n.a. Ratio = 95.0 % PMID[722748]
NPT2 Others Unspecified n.a. Activity = 0.98 uM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Activity = 7.95 nmol PMID[20155971]
NPT2 Others Unspecified n.a. Activity = 5.82 nmol PMID[11929285]
NPT20913 Tissue Whole blood Homo sapiens Retention_time = 4.94 min DOI[10.1007/s00044-012-9977-1]
NPT2 Others Unspecified n.a. Ratio Ki = 43.0 n.a. PMID[26110443]
NPT2 Others Unspecified n.a. Ki = 201.0 nM PMID[21135175]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC329793 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
1.0 High Similarity NPC600762
0.7794 Intermediate Similarity NPC329747
0.7286 Intermediate Similarity NPC478078
0.7123 Intermediate Similarity NPC471304
0.7059 Intermediate Similarity NPC21605
0.7059 Intermediate Similarity NPC215538
0.675 Remote Similarity NPC478074
0.6154 Remote Similarity NPC96321
0.6154 Remote Similarity NPC111993
0.5867 Remote Similarity NPC189812
0.5867 Remote Similarity NPC329688
0.5657 Remote Similarity NPC485894
0.5625 Remote Similarity NPC475910
0.5357 Remote Similarity NPC474192
0.5333 Remote Similarity NPC485921
0.5333 Remote Similarity NPC478082
0.5234 Remote Similarity NPC478081
0.5152 Remote Similarity NPC485962
0.5152 Remote Similarity NPC477065
0.5094 Remote Similarity NPC485893
0.5045 Remote Similarity NPC478080

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC329793 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
1.0 High Similarity NPD4118 Clinical (unspecified phase)

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data