Natural Product: NPC223325

Natural Product IDNPC223325
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 QFBAAHOFCQDCQH-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 21576570
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:0003517] 2-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 QFBAAHOFCQDCQH-UHFFFAOYSA-N
Standard InCHI InChI=1S/C24H26O6/c1-7-24(4,5)17-21(29-6)13(9-8-12(2)3)18(26)16-19(27)14-10-11-15(25)20(28)22(14)30-23(16)17/h7-8,10-11,25-26,28H,1,9H2,2-6H3
SMILES C=CC(C)(C)c1c(c(CC=C(C)C)c(c2c(=O)c3ccc(c(c3oc12)O)O)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   410.17 Volume:   427.004
?
Van der Waals volume.
Dense:   0.961 LogP:   4.455
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.548
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.6
?
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:   0.309 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.321 Fsp3:   0.292
MCE-18:   24.0
?
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:   1
Colloidal aggregators:   0.934 Fluc inhibitor:   0.25
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.781
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.786
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.264 Promiscuous compounds:   0.17

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.099 MDCK Permeability:   -4.78
Pgp-inhibitor:   0.69 Pgp-substrate:   0.03
PAMPA:   0.4
?
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):   0.246
20% Bioavailability (F20%):   0.999 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.973
Plasma Protein Binding (PPB):   96.118% Volume Distribution (VD):   0.056
Fu: 3.573%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.997
BSEP inhibitor:   0.936

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.82 CYP2C19-substrate:   0.991
CYP2C9-inhibitor:   0.017 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.921
CYP3A4-inhibitor:   0.16 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):  8.172 Half-life (T1/2):  1.42

ADMET: Toxicity

hERG Blockers:  0.026 hERG Blockers (10um):  0.493
Human Hepatotoxicity (H-HT):  0.437 Drug-induced Liver Injury (DILI):  0.861
AMES Toxicity:  0.602 Rat Oral Acute Toxicity:  0.825
Maximum Recommended Daily Dose:  0.654 Skin Sensitization:  0.969
Carcinogencity:  0.601 Eye Corrosion:  0.003
Eye Irritation:  0.863 Respiratory Toxicity:  0.865
Drug-induced Neurotoxicity:  0.069 Ototoxicity:  0.435
Hematotoxicity:  0.159 Drug-induced Nephrotoxicity:  0.161
Genotoxicity:  0.93 RPMI-8226 Immunitoxicity:  0.044
A549 Cytotoxicity:  0.551 Hek293 Cytotoxicity:  0.442
BCF:   1.948
?
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:   4.731
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.582
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.919
?
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]
NPO16861 Garcinia nigrolineata Species Clusiaceae Eukaryota Twigs n.a. n.a. PMID[16124764]
NPO15264 Garcinia paucinervis Species Clusiaceae Eukaryota n.a. n.a. n.a. PMID[20594858]
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]
NPO16861 Garcinia nigrolineata Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15264 Garcinia paucinervis Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16861 Garcinia nigrolineata Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16861 Garcinia nigrolineata Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16861 Garcinia nigrolineata Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15264 Garcinia paucinervis Species Clusiaceae 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
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 NPC223325 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
0.7969 Intermediate Similarity NPC117992
0.6765 Remote Similarity NPC304008
0.6716 Remote Similarity NPC219867
0.6667 Remote Similarity NPC188433
0.6667 Remote Similarity NPC478523
0.6667 Remote Similarity NPC187745
0.6197 Remote Similarity NPC168247
0.6081 Remote Similarity NPC611564
0.6 Remote Similarity NPC472277
0.6 Remote Similarity NPC103238
0.5753 Remote Similarity NPC230149
0.5479 Remote Similarity NPC78225
0.5443 Remote Similarity NPC483041
0.5405 Remote Similarity NPC113906
0.5362 Remote Similarity NPC222341
0.5342 Remote Similarity NPC472281
0.5211 Remote Similarity NPC115853
0.52 Remote Similarity NPC152951
0.5128 Remote Similarity NPC483038
0.5062 Remote Similarity NPC57715

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC223325 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