Natural Product: NPC124269

Natural Product IDNPC124269
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4-Geranyloxy-2,6-Dihydroxybenzophenone
IUPAC Name [4-[(2E)-3,7-dimethylocta-2,6-dienoxy]-2,6-dihydroxyphenyl]-phenylmethanone
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL510517
PubChem CID 44575287
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0000120] Benzophenones

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 CPWFSCYLMXLCDK-SFQUDFHCSA-N
Standard InCHI InChI=1S/C23H26O4/c1-16(2)8-7-9-17(3)12-13-27-19-14-20(24)22(21(25)15-19)23(26)18-10-5-4-6-11-18/h4-6,8,10-12,14-15,24-25H,7,9,13H2,1-3H3/b17-12+
SMILES C/C(=CCOc1cc(O)c(c(c1)O)C(=O)c1ccccc1)/CCC=C(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   366.18 Volume:   400.684
?
Van der Waals volume.
Dense:   0.914 LogP:   6.443
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.143
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.278
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   15.0
TPSA:   66.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.485 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.528 Fsp3:   0.261
MCE-18:   14.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.963 Fluc inhibitor:   0.32
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.398
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.702
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.617 Promiscuous compounds:   0.124

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.197 MDCK Permeability:   -4.789
Pgp-inhibitor:   0.95 Pgp-substrate:   0.009
PAMPA:   0.026
?
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):   0.002
20% Bioavailability (F20%):   0.005 30% Bioavailability (F30%):   0.148
50% Bioavailability (F50%):   0.941

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.08 MRP1:   0.57
Plasma Protein Binding (PPB):   97.923% Volume Distribution (VD):   -0.019
Fu: 1.759%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.542
BSEP inhibitor:   0.903

ADMET: Metabolism

CYP1A2-inhibitor:   0.02 CYP1A2-substrate:   0.997
CYP2C19-inhibitor:   0.027 CYP2C19-substrate:   0.552
CYP2C9-inhibitor:   0.1 CYP2C9-substrate:   0.69
CYP2D6-inhibitor:   0.983 CYP2D6-substrate:   0.028
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.958
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.994
HLM stability:   0.99
?
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):  7.134 Half-life (T1/2):  0.832

ADMET: Toxicity

hERG Blockers:  0.205 hERG Blockers (10um):  0.617
Human Hepatotoxicity (H-HT):  0.519 Drug-induced Liver Injury (DILI):  0.713
AMES Toxicity:  0.233 Rat Oral Acute Toxicity:  0.099
Maximum Recommended Daily Dose:  0.435 Skin Sensitization:  0.929
Carcinogencity:  0.149 Eye Corrosion:  0.0
Eye Irritation:  0.91 Respiratory Toxicity:  0.938
Drug-induced Neurotoxicity:  0.251 Ototoxicity:  0.414
Hematotoxicity:  0.268 Drug-induced Nephrotoxicity:  0.567
Genotoxicity:  0.259 RPMI-8226 Immunitoxicity:  0.116
A549 Cytotoxicity:  0.553 Hek293 Cytotoxicity:  0.414
BCF:   2.308
?
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:   6.751
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.277
?
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
NPO9520 Cratoxylum sumatranum Species Hypericaceae Eukaryota n.a. leaf n.a. PMID[11908969]
NPO9520 Cratoxylum sumatranum Species Hypericaceae Eukaryota n.a. stem n.a. PMID[11908969]
NPO9520 Cratoxylum sumatranum Species Hypericaceae Eukaryota n.a. twig n.a. PMID[11908969]
NPO22504 Tovomita longifolia Species Clusiaceae Eukaryota leaves n.a. n.a. PMID[16562847]
NPO16745 Scorzonera judaica Species Asteraceae Eukaryota n.a. tuberous root n.a. PMID[21650157]
NPO16745 Scorzonera judaica Species Asteraceae Eukaryota roots Daba desert reserve (50 km South of Amman), Jordan 2009-APR PMID[21650157]
NPO13263 Verbena brasiliensis Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19227 Hippoglossus hippoglossus Species Pleuronectidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16038 Ribes rubrum Species Grossulariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22504 Tovomita longifolia Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6106 Hymeniacidon perlevis Species Halichondriidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17438 Polygala virgata Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9520 Cratoxylum sumatranum Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16745 Scorzonera judaica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18657 Galanthus gracilis Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18005 Artemisia leucodes Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11770 Amphicome emodi n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO14950 Ardisia polycephala Species Primulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18995 Gaultheria itoana Species Ericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19359 Parmotrema delicatulum Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19560 Populus italica Species Salicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19501 Pseudosuberites hyalinus Species Suberitidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19227 Hippoglossus hippoglossus Species Pleuronectidae Eukaryota n.a. n.a. Database[FooDB]
NPO19227 Hippoglossus hippoglossus Species Pleuronectidae Eukaryota n.a. n.a. Database[FooDB]
NPO16038 Ribes rubrum Species Grossulariaceae Eukaryota Fruits n.a. Database[FooDB]
NPO16038 Ribes rubrum Species Grossulariaceae Eukaryota n.a. n.a. Database[FooDB]
NPO16038 Ribes rubrum Species Grossulariaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO16038 Ribes rubrum Species Grossulariaceae Eukaryota Fruits n.a. Database[Phenol-Explorer]
NPO11770 Amphicome emodi n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO14950 Ardisia polycephala Species Primulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6106 Hymeniacidon perlevis Species Halichondriidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16745 Scorzonera judaica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18995 Gaultheria itoana Species Ericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19227 Hippoglossus hippoglossus Species Pleuronectidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17438 Polygala virgata Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19560 Populus italica Species Salicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18657 Galanthus gracilis Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18005 Artemisia leucodes Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19359 Parmotrema delicatulum Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13263 Verbena brasiliensis Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16038 Ribes rubrum Species Grossulariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22504 Tovomita longifolia Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9520 Cratoxylum sumatranum Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19501 Pseudosuberites hyalinus Species Suberitidae 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 GI50 = 4.8 ug.mL-1 PMID[16562847]
NPT397 Cell line NCI-H460 Homo sapiens GI50 = 4.4 ug.mL-1 PMID[16562847]
NPT395 Cell line SF-268 Homo sapiens GI50 = 2.0 ug.mL-1 PMID[16562847]
NPT602 Organism Mycobacterium smegmatis Mycobacterium smegmatis MIC = 12.5 ug.mL-1 PMID[16562847]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 12.5 ug.mL-1 PMID[16562847]

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 NPC124269 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
0.6923 Remote Similarity NPC203817
0.6545 Remote Similarity NPC236974
0.6429 Remote Similarity NPC121243
0.5781 Remote Similarity NPC40356
0.5455 Remote Similarity NPC294387
0.5323 Remote Similarity NPC156910
0.5254 Remote Similarity NPC470393
0.5238 Remote Similarity NPC105157
0.5167 Remote Similarity NPC192596
0.5082 Remote Similarity NPC479053
0.5077 Remote Similarity NPC602136

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC124269 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