Natural Product: NPC36269

Natural Product IDNPC36269
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 UXJRNDGACFTLIK-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 14630662
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000025] Phenanthrenes and derivatives
        • [CHEMONTID:0000223] Hydrophenanthrenes

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 UXJRNDGACFTLIK-UHFFFAOYSA-N
Standard InCHI InChI=1S/C22H20O4/c1-26-22-19(10-13-2-6-16(23)7-3-13)20(25)12-15-5-4-14-11-17(24)8-9-18(14)21(15)22/h2-3,6-9,11-12,23-25H,4-5,10H2,1H3
SMILES COc1c(Cc2ccc(cc2)O)c(cc2CCc3cc(ccc3-c12)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   348.14 Volume:   366.275
?
Van der Waals volume.
Dense:   0.95 LogP:   3.206
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.261
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.678
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   22.0
TPSA:   69.92
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.664 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.491 Fsp3:   0.182
MCE-18:   47.385
?
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:   0.966 Fluc inhibitor:   0.222
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.65
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.372
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.296 Promiscuous compounds:   0.124

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.869 MDCK Permeability:   -4.805
Pgp-inhibitor:   0.024 Pgp-substrate:   0.283
PAMPA:   0.876
?
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):   0.011
20% Bioavailability (F20%):   0.942 30% Bioavailability (F30%):   0.813
50% Bioavailability (F50%):   0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.005 MRP1:   0.939
Plasma Protein Binding (PPB):   95.823% Volume Distribution (VD):   0.349
Fu: 6.263%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.978
OATP1B3 inhibitor:   0.965 BCRP inhibitor:   0.004
BSEP inhibitor:   0.947

ADMET: Metabolism

CYP1A2-inhibitor:   0.908 CYP1A2-substrate:   0.063
CYP2C19-inhibitor:   0.806 CYP2C19-substrate:   0.871
CYP2C9-inhibitor:   0.745 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.998 CYP2D6-substrate:   0.818
CYP3A4-inhibitor:   0.727 CYP3A4-substrate:   0.995
CYP2B6-substrate:   0.002 CYP2C8-inhibitor:   0.999
HLM stability:   0.969
?
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):  8.12 Half-life (T1/2):  1.366

ADMET: Toxicity

hERG Blockers:  0.233 hERG Blockers (10um):  0.814
Human Hepatotoxicity (H-HT):  0.637 Drug-induced Liver Injury (DILI):  0.048
AMES Toxicity:  0.596 Rat Oral Acute Toxicity:  0.358
Maximum Recommended Daily Dose:  0.73 Skin Sensitization:  0.958
Carcinogencity:  0.557 Eye Corrosion:  0.013
Eye Irritation:  0.971 Respiratory Toxicity:  0.95
Drug-induced Neurotoxicity:  0.391 Ototoxicity:  0.25
Hematotoxicity:  0.069 Drug-induced Nephrotoxicity:  0.066
Genotoxicity:  0.793 RPMI-8226 Immunitoxicity:  0.056
A549 Cytotoxicity:  0.426 Hek293 Cytotoxicity:  0.891
BCF:   1.555
?
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:   4.927
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.461
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.229
?
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
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[1402962]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota n.a. n.a. n.a. PMID[15686910]
NPO11479 Sargassum siliquastrum Species Sargassaceae Eukaryota n.a. n.a. n.a. PMID[15921416]
NPO11479 Sargassum siliquastrum Species Sargassaceae Eukaryota n.a. subtidal zone (0-2 m) off the southwestern shore of Jeju Island, Korea 2003-Apr PMID[18817444]
NPO11479 Sargassum siliquastrum Species Sargassaceae Eukaryota n.a. n.a. n.a. PMID[19006667]
NPO11479 Sargassum siliquastrum Species Sargassaceae Eukaryota n.a. n.a. n.a. PMID[21377877]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota Fibrous Roots n.a. n.a. PMID[25760525]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota Flower Buds n.a. n.a. PMID[26977531]
NPO7428 Bletilla formosana Species Orchidaceae Eukaryota Rhizomes n.a. n.a. PMID[27525452]
NPO11479 Sargassum siliquastrum Species Sargassaceae Eukaryota n.a. n.a. n.a. PMID[28720331]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota n.a. n.a. n.a. PMID[31415170]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[34770801]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[36985392]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[37836118]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[39684253]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[39699537]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[8904847]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11479 Sargassum siliquastrum Species Sargassaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. Database[FooDB]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. Database[FooDB]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota Stem n.a. n.a. Database[FooDB]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota Essential Oil n.a. n.a. Database[FooDB]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota Bark n.a. n.a. Database[FooDB]
NPO7428 Bletilla formosana Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7428 Bletilla formosana Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7428 Bletilla formosana Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8787 Ariocarpus scapharostrus Species Cactaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15591 Tolpis webbii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11479 Sargassum siliquastrum Species Sargassaceae 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
NPT34 Cell line BV-2 Mus musculus IC50 = 34600.0 nM PMID[31415170]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 200.0 nM PMID[27525452]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 2000.0 nM PMID[27525452]

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 NPC36269 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
0.7407 Intermediate Similarity NPC37410
0.6667 Remote Similarity NPC105620
0.5882 Remote Similarity NPC228503
0.5833 Remote Similarity NPC282508
0.566 Remote Similarity NPC108198
0.5362 Remote Similarity NPC478413
0.5345 Remote Similarity NPC210881
0.5263 Remote Similarity NPC258780
0.5179 Remote Similarity NPC200557

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC36269 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