Natural Product: NPC189473

Natural Product IDNPC189473
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Garcinone B
IUPAC Name 5,9,11-trihydroxy-3,3-dimethyl-10-(3-methylbut-2-enyl)pyrano[3,2-a]xanthen-12-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL560332
PubChem CID 5495928
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 HVXHJNVYRXRHNX-UHFFFAOYSA-N
Standard InCHI InChI=1S/C23H22O6/c1-11(2)5-6-12-14(24)9-17-19(20(12)26)21(27)18-13-7-8-23(3,4)29-22(13)15(25)10-16(18)28-17/h5,7-10,24-26H,6H2,1-4H3
SMILES CC(=CCc1c(O)cc2c(c1O)c(=O)c1c(o2)cc(c2c1C=CC(O2)(C)C)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   394.14 Volume:   401.152
?
Van der Waals volume.
Dense:   0.983 LogP:   4.348
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.504
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.455
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   23.0
TPSA:   100.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.428 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.356 Fsp3:   0.261
MCE-18:   55.862
?
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:   0.826 Fluc inhibitor:   0.587
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.938
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.802
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.268 Promiscuous compounds:   0.216

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.058 MDCK Permeability:   -4.727
Pgp-inhibitor:   0.886 Pgp-substrate:   0.391
PAMPA:   0.083
?
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):   0.007
20% Bioavailability (F20%):   0.248 30% Bioavailability (F30%):   0.901
50% Bioavailability (F50%):   0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.216 MRP1:   0.967
Plasma Protein Binding (PPB):   94.199% Volume Distribution (VD):   0.261
Fu: 7.195%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.948
OATP1B3 inhibitor:   0.712 BCRP inhibitor:   0.867
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.086 CYP2C19-substrate:   0.998
CYP2C9-inhibitor:   0.026 CYP2C9-substrate:   0.006
CYP2D6-inhibitor:   0.041 CYP2D6-substrate:   0.962
CYP3A4-inhibitor:   0.007 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):  1.942 Half-life (T1/2):  1.416

ADMET: Toxicity

hERG Blockers:  0.052 hERG Blockers (10um):  0.563
Human Hepatotoxicity (H-HT):  0.479 Drug-induced Liver Injury (DILI):  0.747
AMES Toxicity:  0.748 Rat Oral Acute Toxicity:  0.819
Maximum Recommended Daily Dose:  0.741 Skin Sensitization:  0.916
Carcinogencity:  0.747 Eye Corrosion:  0.016
Eye Irritation:  0.968 Respiratory Toxicity:  0.977
Drug-induced Neurotoxicity:  0.053 Ototoxicity:  0.178
Hematotoxicity:  0.089 Drug-induced Nephrotoxicity:  0.162
Genotoxicity:  0.844 RPMI-8226 Immunitoxicity:  0.086
A549 Cytotoxicity:  0.348 Hek293 Cytotoxicity:  0.688
BCF:   1.918
?
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:   4.759
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.602
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.968
?
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
NPO3806 Garcinia morella Species Clusiaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0040-4039(00)90246-6]
NPO7811 Scleronephthya pallida Species Nephtheidae Eukaryota n.a. n.a. n.a. PMID[10075773]
NPO24928 Cratoxylum cochinchinense Species Hypericaceae Eukaryota n.a. n.a. n.a. PMID[15182859]
NPO24928 Cratoxylum cochinchinense Species Hypericaceae Eukaryota n.a. root n.a. PMID[16310231]
NPO24928 Cratoxylum cochinchinense Species Hypericaceae Eukaryota n.a. root n.a. PMID[16651783]
NPO10376 Arcyria denudata Species Trichiidae Eukaryota n.a. n.a. n.a. PMID[16933891]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota n.a. n.a. n.a. PMID[18464091]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota n.a. n.a. n.a. PMID[18558747]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota n.a. n.a. n.a. PMID[19299148]
NPO6871 Garcinia staudtii Species Clusiaceae Eukaryota twigs n.a. n.a. PMID[19604701]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota stem bark Pangradin village, Jasinga, West Java, Indonesia 2005-AUG PMID[19839614]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota n.a. n.a. n.a. PMID[20817450]
NPO24928 Cratoxylum cochinchinense Species Hypericaceae Eukaryota n.a. stem n.a. PMID[21428375]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota n.a. pericarp n.a. PMID[24555285]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota n.a. n.a. n.a. PMID[24717154]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota fruit hulls Madras, Tamil Nadu, India 1993-MAR PMID[9213587]
NPO3806 Garcinia morella Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9741 Actinopyga agassizi Species Holothuriidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8560 Aplidium tabascum Species Polyclinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3707 Chromatium okenii Species Chromatiaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO10056 Nicotiana sylvestris Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22337 Garcinia dulcis Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9717 Wibelia divaricata Species Davalliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12600 Trametes cinnabarina Species Coriolaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10221 Streptomyces alboniger Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO27924 Serpocaulon triseriale Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25216 Senecio vellereus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7811 Scleronephthya pallida Species Nephtheidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8927 Poria selecta Species Coccinellidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24928 Cratoxylum cochinchinense Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24931 Myelochroa aurulenta Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3449 Lonicera hypoleuca Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7534 Leptogorgia sarmentosa Species Gorgoniidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4064 Halimodendron halodendron Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10391 Dolomiaea souliei Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8354 Aster bellidiastrum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10376 Arcyria denudata Species Trichiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10849 Eucalyptus camaldulensis Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22337 Garcinia dulcis Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24928 Cratoxylum cochinchinense Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3806 Garcinia morella Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24928 Cratoxylum cochinchinense Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3806 Garcinia morella Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22337 Garcinia dulcis Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10849 Eucalyptus camaldulensis Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10391 Dolomiaea souliei Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3806 Garcinia morella Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10391 Dolomiaea souliei Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO24928 Cratoxylum cochinchinense Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10221 Streptomyces alboniger Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO9741 Actinopyga agassizi Species Holothuriidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3707 Chromatium okenii Species Chromatiaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27924 Serpocaulon triseriale Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10391 Dolomiaea souliei Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4064 Halimodendron halodendron Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10376 Arcyria denudata Species Trichiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8354 Aster bellidiastrum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12600 Trametes cinnabarina Species Coriolaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3449 Lonicera hypoleuca Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3806 Garcinia morella Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22337 Garcinia dulcis Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10056 Nicotiana sylvestris Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7534 Leptogorgia sarmentosa Species Gorgoniidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24931 Myelochroa aurulenta Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10849 Eucalyptus camaldulensis Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8927 Poria selecta Species Coccinellidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7811 Scleronephthya pallida Species Nephtheidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25216 Senecio vellereus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9717 Wibelia divaricata Species Davalliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8560 Aplidium tabascum Species Polyclinidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6871 Garcinia staudtii 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
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 128.0 ug.mL-1 PMID[19604701]

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 NPC189473 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
0.7714 Intermediate Similarity NPC37870
0.7361 Intermediate Similarity NPC239752
0.7042 Intermediate Similarity NPC25152
0.6912 Remote Similarity NPC228785
0.6667 Remote Similarity NPC139036
0.6622 Remote Similarity NPC218313
0.6267 Remote Similarity NPC61010
0.6184 Remote Similarity NPC275780
0.6087 Remote Similarity NPC142339
0.6026 Remote Similarity NPC40491
0.6026 Remote Similarity NPC278052
0.6 Remote Similarity NPC236488
0.5844 Remote Similarity NPC310349
0.5753 Remote Similarity NPC602307
0.561 Remote Similarity NPC278968
0.5526 Remote Similarity NPC236132
0.5479 Remote Similarity NPC119224
0.5476 Remote Similarity NPC7483
0.5476 Remote Similarity NPC74766
0.5443 Remote Similarity NPC23298
0.5432 Remote Similarity NPC481615
0.5395 Remote Similarity NPC217677
0.5349 Remote Similarity NPC39091
0.5342 Remote Similarity NPC100123
0.5316 Remote Similarity NPC236796
0.5301 Remote Similarity NPC238064
0.525 Remote Similarity NPC178964
0.5238 Remote Similarity NPC481613
0.5233 Remote Similarity NPC472449
0.5205 Remote Similarity NPC186397
0.5185 Remote Similarity NPC152659
0.5185 Remote Similarity NPC472450
0.5176 Remote Similarity NPC302762
0.5132 Remote Similarity NPC14353
0.5065 Remote Similarity NPC166054
0.5062 Remote Similarity NPC229632

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC189473 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