Natural Product: NPC479160

Natural Product IDNPC479160
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 XXNWCBDPYXMCST-UHFFFAOYSA-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]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000123] Benzopyrans
        • [CHEMONTID:0003410] 1-benzopyrans
          • [CHEMONTID:0002817] Dibenzopyrans
            • [CHEMONTID:0000200] Xanthenes
              • [CHEMONTID:0000204] Xanthones
                • [CHEMONTID:0003519] 8-prenylated xanthones

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 XXNWCBDPYXMCST-UHFFFAOYSA-N
Standard InCHI InChI=1S/C24H26O6/c1-12(2)6-8-14-16(25)10-17(26)21-22(28)20-15(9-7-13(3)4)23(29-5)18(27)11-19(20)30-24(14)21/h6-7,10-11,25-27H,8-9H2,1-5H3
SMILES CC(=CCc1c(cc(c2c(=O)c3c(CC=C(C)C)c(c(cc3oc12)O)OC)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   410.17 Volume:   427.004
?
Van der Waals volume.
Dense:   0.961 LogP:   5.015
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.761
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.281
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   19.0
TPSA:   100.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.4 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.191 Fsp3:   0.292
MCE-18:   22.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.934 Fluc inhibitor:   0.373
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.989
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.768
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.303 Promiscuous compounds:   0.449

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.02 MDCK Permeability:   -4.694
Pgp-inhibitor:   0.964 Pgp-substrate:   0.598
PAMPA:   0.057
?
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):   0.097
20% Bioavailability (F20%):   0.935 30% Bioavailability (F30%):   0.996
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.968
Plasma Protein Binding (PPB):   94.946% Volume Distribution (VD):   0.209
Fu: 5.046%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.889 BCRP inhibitor:   0.994
BSEP inhibitor:   0.921

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.014 CYP2C9-substrate:   0.87
CYP2D6-inhibitor:   0.965 CYP2D6-substrate:   0.522
CYP3A4-inhibitor:   0.326 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  2.882 Half-life (T1/2):  1.552

ADMET: Toxicity

hERG Blockers:  0.018 hERG Blockers (10um):  0.531
Human Hepatotoxicity (H-HT):  0.468 Drug-induced Liver Injury (DILI):  0.713
AMES Toxicity:  0.704 Rat Oral Acute Toxicity:  0.896
Maximum Recommended Daily Dose:  0.551 Skin Sensitization:  0.955
Carcinogencity:  0.466 Eye Corrosion:  0.0
Eye Irritation:  0.562 Respiratory Toxicity:  0.992
Drug-induced Neurotoxicity:  0.076 Ototoxicity:  0.225
Hematotoxicity:  0.099 Drug-induced Nephrotoxicity:  0.276
Genotoxicity:  0.986 RPMI-8226 Immunitoxicity:  0.045
A549 Cytotoxicity:  0.372 Hek293 Cytotoxicity:  0.664
BCF:   2.095
?
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:   4.996
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.756
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.11
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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
NPO40853 Garcinia tetrandra Species Clusiaceae Eukaryota Stem Bark n.a. n.a. PMID[30978023]
NPO40853 Garcinia tetrandra Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT83 Cell line MCF7 Homo sapiens IC50 > 10000.0 nM PMID[30978023]
NPT91 Cell line KB Homo sapiens IC50 > 10000.0 nM PMID[30978023]
NPT65 Cell line HepG2 Homo sapiens IC50 > 10000.0 nM PMID[30978023]
NPT139 Cell line HT-29 Homo sapiens IC50 > 10000.0 nM PMID[30978023]
NPT20987 Cell line HeLa S3 Homo sapiens IC50 > 10000.0 nM PMID[30978023]

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 NPC479160 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
0.8485 Intermediate Similarity NPC206153
0.8485 Intermediate Similarity NPC271629
0.8095 Intermediate Similarity NPC220313
0.7302 Intermediate Similarity NPC241904
0.7162 Intermediate Similarity NPC479158
0.6765 Remote Similarity NPC478517
0.6667 Remote Similarity NPC228785
0.6418 Remote Similarity NPC14353
0.64 Remote Similarity NPC479155
0.6324 Remote Similarity NPC36852
0.6212 Remote Similarity NPC227122
0.6164 Remote Similarity NPC300727
0.6027 Remote Similarity NPC310349
0.6026 Remote Similarity NPC479157
0.5915 Remote Similarity NPC236132
0.5789 Remote Similarity NPC40491
0.5789 Remote Similarity NPC278052
0.5789 Remote Similarity NPC476242
0.5733 Remote Similarity NPC236521
0.5733 Remote Similarity NPC275780
0.5679 Remote Similarity NPC479159
0.5658 Remote Similarity NPC117854
0.5658 Remote Similarity NPC170245
0.561 Remote Similarity NPC479156
0.56 Remote Similarity NPC248638
0.56 Remote Similarity NPC61010
0.5493 Remote Similarity NPC235018
0.5493 Remote Similarity NPC273538
0.5467 Remote Similarity NPC481608
0.5455 Remote Similarity NPC6588
0.5357 Remote Similarity NPC150977
0.5286 Remote Similarity NPC70433
0.5263 Remote Similarity NPC610891
0.525 Remote Similarity NPC481610
0.5244 Remote Similarity NPC7483
0.5244 Remote Similarity NPC74766
0.5195 Remote Similarity NPC479162
0.5195 Remote Similarity NPC603436
0.519 Remote Similarity NPC479164
0.5185 Remote Similarity NPC481611
0.5132 Remote Similarity NPC471982
0.5132 Remote Similarity NPC604255
0.5128 Remote Similarity NPC152659
0.5128 Remote Similarity NPC479161
0.5068 Remote Similarity NPC602307
0.5067 Remote Similarity NPC130589
0.5065 Remote Similarity NPC25152
0.5065 Remote Similarity NPC32694

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC479160 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
0.5493 Remote Similarity NPD4378 Phase 3

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