Natural Product: NPC129614

Natural Product IDNPC129614
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 XLFLUEOTDUTLCF-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 12444404
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000123] Benzopyrans
        • [CHEMONTID:0003410] 1-benzopyrans
          • [CHEMONTID:0002817] Dibenzopyrans
            • [CHEMONTID:0000200] Xanthenes
              • [CHEMONTID:0000204] Xanthones
                • [CHEMONTID:0003521] Pyranoxanthones

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 XLFLUEOTDUTLCF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H14O5/c1-18(2)7-6-9-14-13(8-11(20)17(9)23-18)22-12-5-3-4-10(19)15(12)16(14)21/h3-8,19-20H,1-2H3
SMILES CC1(C)C=Cc2c3c(cc(c2O1)O)oc1cccc(c1c3=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   310.08 Volume:   308.518
?
Van der Waals volume.
Dense:   1.005 LogP:   2.968
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.733
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.625
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   22.0
TPSA:   79.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.621 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.001 Fsp3:   0.167
MCE-18:   50.286
?
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:   0.459 Fluc inhibitor:   0.639
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.817
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.754
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.378 Promiscuous compounds:   0.172

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.911 MDCK Permeability:   -4.68
Pgp-inhibitor:   0.565 Pgp-substrate:   0.735
PAMPA:   0.131
?
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):   0.003
20% Bioavailability (F20%):   0.113 30% Bioavailability (F30%):   0.718
50% Bioavailability (F50%):   0.978

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.491 MRP1:   0.889
Plasma Protein Binding (PPB):   96.79% Volume Distribution (VD):   -0.117
Fu: 3.147%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.612
OATP1B3 inhibitor:   0.635 BCRP inhibitor:   0.823
BSEP inhibitor:   0.988

ADMET: Metabolism

CYP1A2-inhibitor:   0.121 CYP1A2-substrate:   0.969
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.209
CYP2C9-inhibitor:   0.025 CYP2C9-substrate:   0.041
CYP2D6-inhibitor:   0.012 CYP2D6-substrate:   0.885
CYP3A4-inhibitor:   0.009 CYP3A4-substrate:   0.925
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.965
HLM stability:   0.971
?
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):  1.538 Half-life (T1/2):  1.337

ADMET: Toxicity

hERG Blockers:  0.084 hERG Blockers (10um):  0.495
Human Hepatotoxicity (H-HT):  0.431 Drug-induced Liver Injury (DILI):  0.795
AMES Toxicity:  0.694 Rat Oral Acute Toxicity:  0.628
Maximum Recommended Daily Dose:  0.67 Skin Sensitization:  0.647
Carcinogencity:  0.832 Eye Corrosion:  0.298
Eye Irritation:  0.992 Respiratory Toxicity:  0.856
Drug-induced Neurotoxicity:  0.058 Ototoxicity:  0.115
Hematotoxicity:  0.131 Drug-induced Nephrotoxicity:  0.075
Genotoxicity:  0.607 RPMI-8226 Immunitoxicity:  0.063
A549 Cytotoxicity:  0.158 Hek293 Cytotoxicity:  0.414
BCF:   1.651
?
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:   4.385
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.096
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.321
?
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
NPO16861 Garcinia nigrolineata Species Clusiaceae Eukaryota Leaves n.a. n.a. PMID[14695790]
NPO17858 Juglans cinerea Species Juglandaceae Eukaryota n.a. bark n.a. PMID[14727919]
NPO17858 Juglans cinerea Species Juglandaceae Eukaryota n.a. leaf n.a. PMID[14727919]
NPO17858 Juglans cinerea Species Juglandaceae Eukaryota n.a. xylem n.a. PMID[14727919]
NPO17858 Juglans cinerea Species Juglandaceae Eukaryota n.a. root n.a. PMID[14727919]
NPO16861 Garcinia nigrolineata Species Clusiaceae Eukaryota Twigs n.a. n.a. PMID[16124764]
NPO25837 Euphorbia micractina Species Euphorbiaceae Eukaryota Roots Zhang County, Gansu Province, China 2002-Sep PMID[19702283]
NPO25837 Euphorbia micractina Species Euphorbiaceae Eukaryota n.a. root n.a. PMID[21534583]
NPO19352 Paeonia obovata Species Paeoniaceae Eukaryota n.a. seed n.a. PMID[23497864]
NPO25837 Euphorbia micractina Species Euphorbiaceae Eukaryota Roots n.a. n.a. PMID[23691978]
NPO16861 Garcinia nigrolineata Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25806 Streptomyces violaceus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO19352 Paeonia obovata Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17858 Juglans cinerea Species Juglandaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25837 Euphorbia micractina Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24502 Rosa roxburghii Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26671 Hapalosiphon welwitschii Species Hapalosiphonaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO28994 Acacia horrida Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17858 Juglans cinerea Species Juglandaceae Eukaryota n.a. n.a. Database[FooDB]
NPO17858 Juglans cinerea Species Juglandaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO24502 Rosa roxburghii Species Rosaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19352 Paeonia obovata Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17858 Juglans cinerea Species Juglandaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16861 Garcinia nigrolineata Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24502 Rosa roxburghii Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17858 Juglans cinerea Species Juglandaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19352 Paeonia obovata Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16861 Garcinia nigrolineata Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17858 Juglans cinerea Species Juglandaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26671 Hapalosiphon welwitschii Species Hapalosiphonaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO25837 Euphorbia micractina Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25806 Streptomyces violaceus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO16861 Garcinia nigrolineata Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19352 Paeonia obovata Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19038 Zanha golungensis Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24502 Rosa roxburghii Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28994 Acacia horrida Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26101 Andropogon zizanioides Species Poaceae 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 NPC129614 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
0.7581 Intermediate Similarity NPC139036
0.6522 Remote Similarity NPC236488
0.6338 Remote Similarity NPC189473
0.6081 Remote Similarity NPC239752
0.6081 Remote Similarity NPC481615
0.5844 Remote Similarity NPC481613
0.5256 Remote Similarity NPC474290
0.5238 Remote Similarity NPC603894
0.5147 Remote Similarity NPC470107
0.5147 Remote Similarity NPC230157
0.5068 Remote Similarity NPC166054

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC129614 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