Natural Product: NPC284842

Natural Product IDNPC284842
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Narwedine
IUPAC Name n.a.
Synonyms Narwedine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2146604
PubChem CID 10356588
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0001775] Amaryllidaceae alkaloids
        • [CHEMONTID:0004128] Galanthamine-type amaryllidaceae 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 QENVUHCAYXAROT-YOEHRIQHSA-N
Standard InCHI InChI=1S/C17H19NO3/c1-18-8-7-17-6-5-12(19)9-14(17)21-16-13(20-2)4-3-11(10-18)15(16)17/h3-6,14H,7-10H2,1-2H3/t14-,17-/m0/s1
SMILES COc1ccc2c3c1O[C@@H]1[C@@]3(CCN(C2)C)C=CC(=O)C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   285.14 Volume:   292.548
?
Van der Waals volume.
Dense:   0.975 LogP:   1.053
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.144
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.056
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   21.0
TPSA:   38.77
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.791 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.055 Fsp3:   0.471
MCE-18:   98.56
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.311 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.107
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.371
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.015 Promiscuous compounds:   0.278

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.54 MDCK Permeability:   -4.626
Pgp-inhibitor:   0.103 Pgp-substrate:   0.249
PAMPA:   0.015
?
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%):   0.001 30% Bioavailability (F30%):   0.009
50% Bioavailability (F50%):   0.022

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   1.0 MRP1:   0.897
Plasma Protein Binding (PPB):   24.956% Volume Distribution (VD):   0.325
Fu: 69.943%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.959
OATP1B3 inhibitor:   0.751 BCRP inhibitor:   0.071
BSEP inhibitor:   0.987

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.002
CYP2C19-inhibitor:   0.998 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.664 CYP2C9-substrate:   0.022
CYP2D6-inhibitor:   0.949 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.939 CYP3A4-substrate:   0.019
CYP2B6-substrate:   0.368 CYP2C8-inhibitor:   0.0
HLM stability:   0.46
?
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):  6.027 Half-life (T1/2):  3.969

ADMET: Toxicity

hERG Blockers:  0.388 hERG Blockers (10um):  0.582
Human Hepatotoxicity (H-HT):  0.653 Drug-induced Liver Injury (DILI):  0.216
AMES Toxicity:  0.593 Rat Oral Acute Toxicity:  0.806
Maximum Recommended Daily Dose:  0.742 Skin Sensitization:  0.796
Carcinogencity:  0.798 Eye Corrosion:  0.264
Eye Irritation:  0.684 Respiratory Toxicity:  0.953
Drug-induced Neurotoxicity:  0.854 Ototoxicity:  0.316
Hematotoxicity:  0.581 Drug-induced Nephrotoxicity:  0.692
Genotoxicity:  0.803 RPMI-8226 Immunitoxicity:  0.095
A549 Cytotoxicity:  0.106 Hek293 Cytotoxicity:  0.307
BCF:   1.204
?
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:   3.75
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.35
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.647
?
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
NPO24293 Neorautanenia mitis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[16562843]
NPO33437 amaryllidaceae Family Amaryllidaceae Eukaryota n.a. n.a. n.a. PMID[22921081]
NPO33437 amaryllidaceae Family Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13480 Stereocaulon dactylophyllum Species Stereocaulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26641 Pteroxygonum giraldii Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO272 Pittosporum eugenioides Species Pittosporaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26154 Erythropodium caribaeorum Species Anthothelidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26604 Aralia subcapitata Species Araliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24293 Neorautanenia mitis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24293 Neorautanenia mitis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26604 Aralia subcapitata Species Araliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13480 Stereocaulon dactylophyllum Species Stereocaulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21398 Jasminum laurifolium f. nitidum Species Oleaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26641 Pteroxygonum giraldii Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26154 Erythropodium caribaeorum Species Anthothelidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23091 Halocarpus bidwillii Species Podocarpaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26604 Aralia subcapitata Species Araliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO272 Pittosporum eugenioides Species Pittosporaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24293 Neorautanenia mitis Species Fabaceae 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1160 Cell line BJ Homo sapiens IC50 > 50000.0 nM PMID[22921081]
NPT2468 Cell line G-361 Homo sapiens IC50 > 50000.0 nM PMID[22921081]
NPT165 Cell line HeLa Homo sapiens IC50 > 50000.0 nM PMID[22921081]
NPT83 Cell line MCF7 Homo sapiens IC50 > 50000.0 nM PMID[22921081]
NPT111 Cell line K562 Homo sapiens IC50 > 50000.0 nM PMID[22921081]
NPT404 Cell line CCRF-CEM Homo sapiens IC50 = 31600.0 nM PMID[22921081]

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 NPC284842 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
0.6984 Remote Similarity NPC148014
0.6984 Remote Similarity NPC315707
0.6984 Remote Similarity NPC78359
0.6875 Remote Similarity NPC607345
0.6875 Remote Similarity NPC611663
0.5672 Remote Similarity NPC305985
0.5672 Remote Similarity NPC129603
0.5672 Remote Similarity NPC56540
0.5493 Remote Similarity NPC40389
0.5342 Remote Similarity NPC65490
0.5143 Remote Similarity NPC91341

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC284842 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
0.6984 Remote Similarity NPD2563 Phase 4
0.6875 Remote Similarity NPD2560 Approved
0.5195 Remote Similarity NPD6071 Discontinued

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