Natural Product: NPC155442

Natural Product IDNPC155442
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Actinodaphnine
IUPAC Name n.a.
Synonyms Actinodaphnine; Actinodaphoine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL518088
PubChem CID 160502
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0000381] Aporphines

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 VYJUHRAQPIBWNV-LBPRGKRZSA-N
Standard InCHI InChI=1S/C18H17NO4/c1-21-14-7-11-10(5-13(14)20)4-12-16-9(2-3-19-12)6-15-18(17(11)16)23-8-22-15/h5-7,12,19-20H,2-4,8H2,1H3/t12-/m0/s1
SMILES COc1cc2c(cc1O)C[C@H]1c3c2c2OCOc2cc3CCN1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   311.12 Volume:   307.441
?
Van der Waals volume.
Dense:   1.012 LogP:   1.426
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.784
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.744
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   24.0
TPSA:   59.95
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   5.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.847 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.318 Fsp3:   0.333
MCE-18:   85.417
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.862 Fluc inhibitor:   0.289
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.623
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.287
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.286

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.031 MDCK Permeability:   -4.768
Pgp-inhibitor:   0.005 Pgp-substrate:   0.853
PAMPA:   0.106
?
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):   0.002
20% Bioavailability (F20%):   0.238 30% Bioavailability (F30%):   0.275
50% Bioavailability (F50%):   0.917

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.459 MRP1:   0.974
Plasma Protein Binding (PPB):   76.149% Volume Distribution (VD):   -0.03
Fu: 27.185%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.634
OATP1B3 inhibitor:   0.703 BCRP inhibitor:   0.216
BSEP inhibitor:   0.655

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.175
CYP2C19-inhibitor:   0.992 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.997 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.986
CYP3A4-inhibitor:   0.409 CYP3A4-substrate:   0.987
CYP2B6-substrate:   0.497 CYP2C8-inhibitor:   0.0
HLM stability:   0.305
?
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):  4.325 Half-life (T1/2):  1.842

ADMET: Toxicity

hERG Blockers:  0.448 hERG Blockers (10um):  0.687
Human Hepatotoxicity (H-HT):  0.677 Drug-induced Liver Injury (DILI):  0.328
AMES Toxicity:  0.838 Rat Oral Acute Toxicity:  0.79
Maximum Recommended Daily Dose:  0.933 Skin Sensitization:  0.743
Carcinogencity:  0.622 Eye Corrosion:  0.001
Eye Irritation:  0.376 Respiratory Toxicity:  0.972
Drug-induced Neurotoxicity:  0.868 Ototoxicity:  0.387
Hematotoxicity:  0.162 Drug-induced Nephrotoxicity:  0.623
Genotoxicity:  0.875 RPMI-8226 Immunitoxicity:  0.093
A549 Cytotoxicity:  0.467 Hek293 Cytotoxicity:  0.351
BCF:   1.579
?
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:   3.969
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.348
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.602
?
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
NPO27302 Cinnamomum insularimontanum Species Lauraceae Eukaryota n.a. root n.a. PMID[16168547]
NPO23076 Illigera luzonensis Species Hernandiaceae Eukaryota n.a. n.a. n.a. PMID[9214740]
NPO32857 cassytha filiformis ii Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[9677264]
NPO22727 Avena fatua Species Poaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21569 Helichrysum fulvum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16798 Piper sylvaticum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23076 Illigera luzonensis Species Hernandiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27302 Cinnamomum insularimontanum Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21569 Helichrysum fulvum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22727 Avena fatua Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23076 Illigera luzonensis Species Hernandiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16798 Piper sylvaticum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27302 Cinnamomum insularimontanum Species Lauraceae 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
NPT189 Cell line Vero Chlorocebus aethiops MTC = 95.0 uM PMID[9584402]
NPT189 Cell line Vero Chlorocebus aethiops CC50 = 107000.0 nM PMID[9584402]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 0.0 % PMID[9214740]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 42.7 % PMID[9214740]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 60.5 % PMID[9214740]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 80.3 % PMID[9214740]
NPT177 Tissue Aorta Rattus norvegicus Activity = 41.9 % PMID[9214740]
NPT177 Tissue Aorta Rattus norvegicus Activity = 40.6 % PMID[9214740]
NPT177 Tissue Aorta Rattus norvegicus Activity = 15.5 % PMID[9214740]
NPT20967 Cell line Platelet n.a. Activity = 0.0 % PMID[9677264]

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 NPC155442 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 NPC312918
0.8276 Intermediate Similarity NPC69712
0.8276 Intermediate Similarity NPC220228
0.7541 Intermediate Similarity NPC6152
0.746 Intermediate Similarity NPC152212
0.746 Intermediate Similarity NPC28341
0.697 Remote Similarity NPC186546
0.6935 Remote Similarity NPC298008
0.6885 Remote Similarity NPC26240
0.6866 Remote Similarity NPC135772
0.6716 Remote Similarity NPC57036
0.6716 Remote Similarity NPC600117
0.6462 Remote Similarity NPC189470
0.6462 Remote Similarity NPC191213
0.6406 Remote Similarity NPC609330
0.6364 Remote Similarity NPC470879
0.597 Remote Similarity NPC302713
0.5714 Remote Similarity NPC481950
0.5507 Remote Similarity NPC192135
0.5373 Remote Similarity NPC203784
0.5373 Remote Similarity NPC170503
0.5373 Remote Similarity NPC126519
0.5224 Remote Similarity NPC66341
0.5217 Remote Similarity NPC610238
0.5205 Remote Similarity NPC600341
0.52 Remote Similarity NPC229166
0.5143 Remote Similarity NPC81247
0.5143 Remote Similarity NPC35627
0.5143 Remote Similarity NPC299687
0.5143 Remote Similarity NPC476573
0.507 Remote Similarity NPC608930

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC155442 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
NPD

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