Natural Product: NPC139078

Natural Product IDNPC139078
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 SFLBNAROMBKKJF-QITLCBANSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 SFLBNAROMBKKJF-QITLCBANSA-N
Standard InCHI InChI=1S/C20H22N2O3/c1-24-20(23)16-11-25-10-12-9-22-7-6-14-13-4-2-3-5-17(13)21-19(14)18(22)8-15(12)16/h2-5,11-12,15,18,21H,6-10H2,1H3/t12-,15-,18-/m0/s1
SMILES COC(=O)C1=COC[C@@H]2CN3CCc4c5ccccc5[nH]c4[C@@H]3C[C@H]12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   338.16 Volume:   344.239
?
Van der Waals volume.
Dense:   0.982 LogP:   2.323
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.303
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.2
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   26.0
TPSA:   54.56
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.813 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.853 Fsp3:   0.45
MCE-18:   88.793
?
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:   0.244 Fluc inhibitor:   0.435
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.562
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.401
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.552

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.851 MDCK Permeability:   -4.678
Pgp-inhibitor:   0.012 Pgp-substrate:   0.92
PAMPA:   0.097
?
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%):   0.285 30% Bioavailability (F30%):   0.433
50% Bioavailability (F50%):   0.952

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.701 MRP1:   0.998
Plasma Protein Binding (PPB):   86.834% Volume Distribution (VD):   0.584
Fu: 13.387%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.297
OATP1B3 inhibitor:   0.657 BCRP inhibitor:   0.679
BSEP inhibitor:   0.994

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.014
CYP2C19-inhibitor:   0.534 CYP2C19-substrate:   0.018
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.999
CYP2D6-inhibitor:   0.806 CYP2D6-substrate:   0.181
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.998
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.331
HLM stability:   0.005
?
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):  10.636 Half-life (T1/2):  1.737

ADMET: Toxicity

hERG Blockers:  0.572 hERG Blockers (10um):  0.653
Human Hepatotoxicity (H-HT):  0.492 Drug-induced Liver Injury (DILI):  0.76
AMES Toxicity:  0.726 Rat Oral Acute Toxicity:  0.836
Maximum Recommended Daily Dose:  0.966 Skin Sensitization:  0.945
Carcinogencity:  0.797 Eye Corrosion:  0.0
Eye Irritation:  0.191 Respiratory Toxicity:  0.971
Drug-induced Neurotoxicity:  0.771 Ototoxicity:  0.531
Hematotoxicity:  0.345 Drug-induced Nephrotoxicity:  0.87
Genotoxicity:  0.978 RPMI-8226 Immunitoxicity:  0.063
A549 Cytotoxicity:  0.567 Hek293 Cytotoxicity:  0.673
BCF:   1.129
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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:   3.819
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.069
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.609
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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
NPO10 Alexandrium ostenfeldii Species Pyrocystaceae Eukaryota n.a. n.a. n.a. PMID[16872129]
NPO10 Alexandrium ostenfeldii Species Pyrocystaceae Eukaryota n.a. n.a. n.a. PMID[19572609]
NPO28069.1 Artemisia cana subsp. viscidula Subspecies Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3679 Psilocybe baeocystis Species Strophariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10 Alexandrium ostenfeldii Species Pyrocystaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1824 Callitris rhomboidea Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28069.1 Artemisia cana subsp. viscidula Subspecies Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28069.1 Artemisia cana subsp. viscidula Subspecies Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2744 Aphloia madagascariensis Species Aphloiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3679 Psilocybe baeocystis Species Strophariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1824 Callitris rhomboidea Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10 Alexandrium ostenfeldii Species Pyrocystaceae 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

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 NPC139078 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
0.7632 Intermediate Similarity NPC486449
0.7632 Intermediate Similarity NPC63199
0.7632 Intermediate Similarity NPC111602
0.7632 Intermediate Similarity NPC102338
0.7632 Intermediate Similarity NPC196251
0.7632 Intermediate Similarity NPC273374
0.7342 Intermediate Similarity NPC312870
0.7342 Intermediate Similarity NPC199851
0.7342 Intermediate Similarity NPC294909
0.7342 Intermediate Similarity NPC254240
0.7342 Intermediate Similarity NPC128265
0.7342 Intermediate Similarity NPC604675
0.6463 Remote Similarity NPC107782
0.6463 Remote Similarity NPC486454
0.6145 Remote Similarity NPC486443
0.6145 Remote Similarity NPC486446
0.6 Remote Similarity NPC100898
0.6 Remote Similarity NPC148183
0.6 Remote Similarity NPC131260
0.6 Remote Similarity NPC21084
0.6 Remote Similarity NPC152768
0.6 Remote Similarity NPC605270
0.5882 Remote Similarity NPC175474
0.5882 Remote Similarity NPC99921
0.5833 Remote Similarity NPC486452
0.5833 Remote Similarity NPC74591
0.5795 Remote Similarity NPC603895
0.5765 Remote Similarity NPC313985
0.5765 Remote Similarity NPC249150
0.5765 Remote Similarity NPC33619
0.573 Remote Similarity NPC21638
0.5698 Remote Similarity NPC81654
0.5682 Remote Similarity NPC293861
0.56 Remote Similarity NPC486444
0.56 Remote Similarity NPC649
0.5529 Remote Similarity NPC220151
0.5529 Remote Similarity NPC19692
0.55 Remote Similarity NPC21174
0.5432 Remote Similarity NPC229173
0.5301 Remote Similarity NPC474897
0.5244 Remote Similarity NPC185200
0.5243 Remote Similarity NPC199607
0.5243 Remote Similarity NPC54591
0.5233 Remote Similarity NPC472112
0.5227 Remote Similarity NPC483467

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC139078 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
0.7342 Intermediate Similarity NPD4500 Approved
0.7342 Intermediate Similarity NPD4501 Approved
0.5765 Remote Similarity NPD4601 Phase 4
0.5698 Remote Similarity NPD4600 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