Natural Product: NPC329858

Natural Product IDNPC329858
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Coronaridine
IUPAC Name n.a.
Synonyms Coronaridine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL364613
PubChem CID 73489
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 NVVDQMVGALBDGE-KSWFMABOSA-N
Standard InCHI InChI=1S/C21H26N2O2/c1-3-14-10-13-11-21(20(24)25-2)18-16(8-9-23(12-13)19(14)21)15-6-4-5-7-17(15)22-18/h4-7,13-14,19,22H,3,8-12H2,1-2H3/t13-,14-,19-,21+/m0/s1
SMILES CC[C@H]1C[C@H]2C[C@]3(c4c(CCN(C2)[C@@H]13)c1ccccc1[nH]4)C(=O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   338.2 Volume:   355.382
?
Van der Waals volume.
Dense:   0.952 LogP:   3.176
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.149
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.96
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   24.0
TPSA:   45.33
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   6.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.855 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.003 Fsp3:   0.571
MCE-18:   95.727
?
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:   0.172 Fluc inhibitor:   0.009
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.504
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.351
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.001 Promiscuous compounds:   0.723

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.302 MDCK Permeability:   -5.201
Pgp-inhibitor:   0.046 Pgp-substrate:   0.751
PAMPA:   0.028
?
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):   0.0
20% Bioavailability (F20%):   0.149 30% Bioavailability (F30%):   0.532
50% Bioavailability (F50%):   0.831

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.814 MRP1:   0.992
Plasma Protein Binding (PPB):   89.618% Volume Distribution (VD):   0.475
Fu: 9.199%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.503
OATP1B3 inhibitor:   0.595 BCRP inhibitor:   0.638
BSEP inhibitor:   0.992

ADMET: Metabolism

CYP1A2-inhibitor:   0.998 CYP1A2-substrate:   0.056
CYP2C19-inhibitor:   0.985 CYP2C19-substrate:   0.048
CYP2C9-inhibitor:   0.005 CYP2C9-substrate:   0.94
CYP2D6-inhibitor:   0.737 CYP2D6-substrate:   0.955
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   0.098
CYP2B6-substrate:   0.014 CYP2C8-inhibitor:   0.961
HLM stability:   0.918
?
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):  10.206 Half-life (T1/2):  1.81

ADMET: Toxicity

hERG Blockers:  0.55 hERG Blockers (10um):  0.646
Human Hepatotoxicity (H-HT):  0.641 Drug-induced Liver Injury (DILI):  0.805
AMES Toxicity:  0.696 Rat Oral Acute Toxicity:  0.81
Maximum Recommended Daily Dose:  0.885 Skin Sensitization:  0.944
Carcinogencity:  0.583 Eye Corrosion:  0.001
Eye Irritation:  0.307 Respiratory Toxicity:  0.982
Drug-induced Neurotoxicity:  0.881 Ototoxicity:  0.472
Hematotoxicity:  0.499 Drug-induced Nephrotoxicity:  0.858
Genotoxicity:  0.806 RPMI-8226 Immunitoxicity:  0.108
A549 Cytotoxicity:  0.586 Hek293 Cytotoxicity:  0.709
BCF:   1.836
?
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:   4.183
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.341
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.012
?
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]
NPO9376 Tabernaemontana corymbosa Species Apocynaceae Eukaryota n.a. leaf n.a. PMID[18778099]
NPO9376 Tabernaemontana corymbosa Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[18778099]
NPO31010 Ervatamia hainanensis n.a. n.a. n.a. n.a. n.a. n.a. PMID[20850311]
NPO25727 Tabernaemontana divaricata Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[23944995]
NPO9376 Tabernaemontana corymbosa Species Apocynaceae Eukaryota Leaves n.a. n.a. PMID[24773071]
NPO9376 Tabernaemontana corymbosa Species Apocynaceae Eukaryota stem-bark Pahang, Malaysia 2003-JUN PMID[25919190]
NPO6246 Ervatamia hainanensis Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[26024020]
NPO25727 Tabernaemontana divaricata Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[26231157]
NPO9376 Tabernaemontana corymbosa Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[26918761]
NPO9376 Tabernaemontana corymbosa Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[27077800]
NPO9376 Tabernaemontana corymbosa Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[29319316]
NPO25727 Tabernaemontana divaricata Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[30169038]
NPO9376 Tabernaemontana corymbosa Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[30869890]
NPO9376 Tabernaemontana corymbosa Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[32356659]
NPO32727 peschiera laeta Species n.a. n.a. n.a. n.a. n.a. PMID[7853002]
NPO9376 Tabernaemontana corymbosa Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25727 Tabernaemontana divaricata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO31010 Ervatamia hainanensis n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO9376 Tabernaemontana corymbosa Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO31010 Ervatamia hainanensis n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO25727 Tabernaemontana divaricata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6246 Ervatamia hainanensis Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9376 Tabernaemontana corymbosa Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25727 Tabernaemontana divaricata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]

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
NPT1885 Individual protein Transient receptor potential cation channel subfamily M member 8 Mus musculus IC50 = 16000.0 nM PMID[18183025]
NPT1885 Individual protein Transient receptor potential cation channel subfamily M member 8 Mus musculus IC50 = 3000.0 nM PMID[23454511]
NPT346 Individual protein Transient receptor potential cation channel subfamily A member 1 Homo sapiens Activity = 75.0 % DrugMatrix in vivo data: Hematology
NPT346 Individual protein Transient receptor potential cation channel subfamily A member 1 Homo sapiens EC50 = 16000.0 nM PMID[14518939]
NPT66 Individual protein Acetylcholinesterase Electrophorus electricus IC50 = 8600.0 nM PMID[23684893]
NPT472 Individual protein Vanilloid receptor Homo sapiens IC50 = 170000.0 nM PMID[24467317]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT91 Cell line KB Homo sapiens IC50 = 11.5 ug.mL-1 PMID[10514299]
NPT91 Cell line KB Homo sapiens IC50 = 2.6 ug.mL-1 PMID[16413779]
NPT762 Cell line A-431 Homo sapiens ED50 = 19.1 ug ml-1 PMID[16989516]
NPT1851 Cell line Col2 Homo sapiens ED50 > 20.0 ug ml-1 PMID[11929285]
NPT2049 Cell line HT Homo sapiens ED50 > 20.0 ug ml-1 PMID[11929285]
NPT91 Cell line KB Homo sapiens ED50 = 13.6 ug ml-1 PMID[11929285]
NPT858 Cell line LNCaP Homo sapiens ED50 = 10.7 ug ml-1 PMID[11929285]
NPT1034 Cell line Lu1 Homo sapiens ED50 = 10.9 ug ml-1 PMID[11929285]
NPT147 Cell line SK-MEL-2 Homo sapiens ED50 > 20.0 ug ml-1 PMID[11929285]
NPT168 Cell line P388 Mus musculus ED50 = 3.8 ug ml-1 Open TG-GATES in vivo data: Biochemistry
NPT133 Cell line ZR-75-1 Homo sapiens ED50 > 20.0 ug ml-1 PMID[22939698]
NPT179 Cell line A2780 Homo sapiens IC50 = 9.9 ug.mL-1 PMID[19132934]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 25500.0 nM DrugMatrix in vitro pharmacology data
NPT2615 Cell line HEK-293T Homo sapiens IC50 > 40000.0 nM Open TG-GATES in vivo data: Pathology
NPT71 Cell line HEK293 Homo sapiens IC50 = 31700.0 nM Open TG-GATES in vivo data: Pathology
NPT2170 Cell line RKO Homo sapiens IC50 > 40000.0 nM PMID[15646539]
NPT660 Cell line SW480 Homo sapiens IC50 = 10400.0 nM PMID[15646539]
NPT393 Cell line HCT-116 Homo sapiens IC50 = 11600.0 nM PMID[26225905]
NPT165 Cell line HeLa Homo sapiens EC50 > 40000.0 nM PMID[32356659]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. ED50 = 7.5 ug ml-1 PMID[7853002]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. ED50 = 1.9 ug ml-1 PMID[7853002]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. ED50 = 11.2 ug ml-1 PMID[7853002]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. ED50 = 12.0 ug ml-1 PMID[7853002]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 24400.0 nM PMID[26231157]
NPT2 Others Unspecified n.a. IC50 = 5800.0 nM PMID[10346965]

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 NPC329858 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
0.8529 High Similarity NPC482061
0.8406 Intermediate Similarity NPC485936
0.8406 Intermediate Similarity NPC485937
0.7746 Intermediate Similarity NPC473041
0.7639 Intermediate Similarity NPC96321
0.7639 Intermediate Similarity NPC111993
0.7534 Intermediate Similarity NPC469928
0.7534 Intermediate Similarity NPC330009
0.7162 Intermediate Similarity NPC485938
0.6889 Remote Similarity NPC485963
0.6623 Remote Similarity NPC314333
0.6623 Remote Similarity NPC606568
0.6538 Remote Similarity NPC473105
0.6526 Remote Similarity NPC17437
0.6458 Remote Similarity NPC485933
0.6458 Remote Similarity NPC485970
0.6456 Remote Similarity NPC474192
0.6421 Remote Similarity NPC485969
0.6392 Remote Similarity NPC475666
0.6224 Remote Similarity NPC81939
0.6078 Remote Similarity NPC485913
0.6078 Remote Similarity NPC485960
0.598 Remote Similarity NPC485922
0.5794 Remote Similarity NPC488883
0.5755 Remote Similarity NPC488882
0.5755 Remote Similarity NPC485918
0.5755 Remote Similarity NPC485915
0.5732 Remote Similarity NPC485887
0.5701 Remote Similarity NPC605382
0.5688 Remote Similarity NPC485945
0.5688 Remote Similarity NPC485917
0.5688 Remote Similarity NPC485954
0.5686 Remote Similarity NPC485966
0.5663 Remote Similarity NPC485941
0.5648 Remote Similarity NPC485935
0.56 Remote Similarity NPC21605
0.56 Remote Similarity NPC215538
0.5596 Remote Similarity NPC471303
0.5395 Remote Similarity NPC63157
0.5395 Remote Similarity NPC473868
0.5294 Remote Similarity NPC485964
0.519 Remote Similarity NPC189812
0.519 Remote Similarity NPC329688
0.5176 Remote Similarity NPC485884
0.5111 Remote Similarity NPC485947

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC329858 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
0.6623 Remote Similarity NPD4499 Approved
0.6139 Remote Similarity NPD8358 Approved

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