Natural Product: NPC152097

Natural Product IDNPC152097
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Geroquinol
IUPAC Name 2-[(2E)-3,7-dimethylocta-2,6-dienyl]benzene-1,4-diol
Synonyms Geroquinol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL459815
PubChem CID 5281857
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001534] Quinone and hydroquinone lipids
          • [CHEMONTID:0002801] Prenylated hydroquinones

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 ZSCRTFONTNMQBL-NTUHNPAUSA-N
Standard InCHI InChI=1S/C16H22O2/c1-12(2)5-4-6-13(3)7-8-14-11-15(17)9-10-16(14)18/h5,7,9-11,17-18H,4,6,8H2,1-3H3/b13-7+
SMILES C/C(=CCc1cc(O)ccc1O)/CCC=C(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   246.16 Volume:   281.134
?
Van der Waals volume.
Dense:   0.876 LogP:   4.792
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.523
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.814
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   8.0
TPSA:   40.46
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   2.0 Rings:   1.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.599 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.556 Fsp3:   0.375
MCE-18:   8.0
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.363 Fluc inhibitor:   0.05
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.005
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.045
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.961 Promiscuous compounds:   0.343

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.697 MDCK Permeability:   -4.723
Pgp-inhibitor:   0.687 Pgp-substrate:   0.001
PAMPA:   0.035
?
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):   0.019
20% Bioavailability (F20%):   0.995 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.231
Plasma Protein Binding (PPB):   96.492% Volume Distribution (VD):   0.115
Fu: 3.409%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.975
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.797
BSEP inhibitor:   0.909

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.976
CYP2C19-inhibitor:   0.939 CYP2C19-substrate:   0.894
CYP2C9-inhibitor:   0.996 CYP2C9-substrate:   0.083
CYP2D6-inhibitor:   0.998 CYP2D6-substrate:   0.458
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.044 CYP2C8-inhibitor:   1.0
HLM stability:   0.991
?
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):  15.505 Half-life (T1/2):  1.387

ADMET: Toxicity

hERG Blockers:  0.123 hERG Blockers (10um):  0.669
Human Hepatotoxicity (H-HT):  0.629 Drug-induced Liver Injury (DILI):  0.265
AMES Toxicity:  0.222 Rat Oral Acute Toxicity:  0.457
Maximum Recommended Daily Dose:  0.4 Skin Sensitization:  0.989
Carcinogencity:  0.4 Eye Corrosion:  0.081
Eye Irritation:  0.957 Respiratory Toxicity:  0.901
Drug-induced Neurotoxicity:  0.289 Ototoxicity:  0.494
Hematotoxicity:  0.212 Drug-induced Nephrotoxicity:  0.261
Genotoxicity:  0.392 RPMI-8226 Immunitoxicity:  0.071
A549 Cytotoxicity:  0.472 Hek293 Cytotoxicity:  0.401
BCF:   2.227
?
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:   5.177
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.176
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.79
?
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
NPO28180 Ornithogalum saundersiae Species Hyacinthaceae Eukaryota n.a. bulb n.a. DOI[10.1016/S0960-894X(97)00071-1]
NPO28180 Ornithogalum saundersiae Species Hyacinthaceae Eukaryota bulbs n.a. n.a. PMID[11170674]
NPO4211 Negombata corticata Species Latrunculiidae Eukaryota n.a. formosan n.a. PMID[20718475]
NPO40780 Amaroucium multiplicatum Species n.a. n.a. n.a. n.a. n.a. PMID[2607356]
NPO40784 Aplidium antillense Species n.a. n.a. n.a. n.a. n.a. PMID[3404153]
NPO9651 Psidium cattleianum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[34486118]
NPO28180 Ornithogalum saundersiae Species Hyacinthaceae Eukaryota n.a. bulb n.a. PMID[7586067]
NPO29107 Vellozia patens Species Velloziaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO40780 Amaroucium multiplicatum Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO926 Adiantum raddianum Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9651 Psidium cattleianum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO40784 Aplidium antillense Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO26142 Carex fedia Species Cyperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4211 Negombata corticata Species Latrunculiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28180 Ornithogalum saundersiae Species Hyacinthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28465 Paraschistochila pinnatifolia Species Schistochilaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29351 Streptomyces gangtokensis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO29138 Tetracera rutenbergii Species Dilleniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29179 Usnea cavernosa Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9651 Psidium cattleianum Species Myrtaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO9651 Psidium cattleianum Species Myrtaceae Eukaryota n.a. n.a. Database[FooDB]
NPO9651 Psidium cattleianum Species Myrtaceae Eukaryota Fruits n.a. Database[FooDB]
NPO28180 Ornithogalum saundersiae Species Hyacinthaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28180 Ornithogalum saundersiae Species Hyacinthaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO926 Adiantum raddianum Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29107 Vellozia patens Species Velloziaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28465 Paraschistochila pinnatifolia Species Schistochilaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26142 Carex fedia Species Cyperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29138 Tetracera rutenbergii Species Dilleniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9651 Psidium cattleianum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29351 Streptomyces gangtokensis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO29179 Usnea cavernosa Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28180 Ornithogalum saundersiae Species Hyacinthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4211 Negombata corticata Species Latrunculiidae 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
NPT91 Cell line KB Homo sapiens IC50 = 4.3 ug.mL-1 PMID[3404153]
NPT168 Cell line P388 Mus musculus IC50 = 0.034 ug.mL-1 PMID[3404153]
NPT172 Organism Proteus mirabilis Proteus mirabilis MIC > 256.0 ug.mL-1 PMID[3404153]
NPT729 Organism Micrococcus luteus Micrococcus luteus MIC = 12.5 ug.mL-1 PMID[7714539]
NPT1084 Subcellular Liver microsomes Rattus norvegicus IC50 = 0.1 ug.mL-1 PMID[2607356]
NPT173 Organism Klebsiella pneumoniae Klebsiella pneumoniae MIC > 256.0 ug.mL-1 PMID[3404153]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC = 6.25 ug.mL-1 PMID[7714539]
NPT20 Organism Candida albicans Candida albicans MIC = 25.0 ug.mL-1 PMID[7714539]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 64.0 ug.mL-1 PMID[3404153]
NPT175 Organism Enterococcus faecalis Enterococcus faecalis MIC = 64.0 ug.mL-1 PMID[3404153]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MIC > 256.0 ug.mL-1 PMID[3404153]
NPT19 Organism Escherichia coli Escherichia coli MIC > 256.0 ug.mL-1 PMID[3404153]
NPT3495 Organism Morganella morganii Morganella morganii MIC > 256.0 ug.mL-1 PMID[3404153]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MBC = 2.0 ug ml-1 PMID[3404153]
NPT175 Organism Enterococcus faecalis Enterococcus faecalis MBC = 1.0 ug ml-1 PMID[3404153]
NPT1248 Organism Serratia marcescens Serratia marcescens MIC = 128.0 ug.mL-1 PMID[3404153]
NPT1248 Organism Serratia marcescens Serratia marcescens MBC > 4.0 ug ml-1 PMID[3404153]
NPT2 Others Unspecified n.a. IC50 = 0.2 ug.mL-1 PMID[2607356]

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
- Gambusia affinis LC50 = 4.6 ppm PMID[7714539]
- Artemia salina LC50 = 0.01 ppm PMID[7714539]

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 NPC152097 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
0.9474 High Similarity NPC260775
0.9474 High Similarity NPC130756
0.9474 High Similarity NPC70677
0.9474 High Similarity NPC12931
0.7907 Intermediate Similarity NPC98392
0.7027 Intermediate Similarity NPC609473
0.68 Remote Similarity NPC155072
0.6444 Remote Similarity NPC477685
0.6304 Remote Similarity NPC76400
0.6078 Remote Similarity NPC4493
0.5926 Remote Similarity NPC228609
0.5769 Remote Similarity NPC320439
0.5652 Remote Similarity NPC12640
0.5532 Remote Similarity NPC479914
0.549 Remote Similarity NPC144343
0.5472 Remote Similarity NPC474890
0.5472 Remote Similarity NPC273282
0.5417 Remote Similarity NPC269414
0.537 Remote Similarity NPC24125
0.5306 Remote Similarity NPC201662
0.5283 Remote Similarity NPC483761
0.5283 Remote Similarity NPC166995
0.5263 Remote Similarity NPC267846
0.52 Remote Similarity NPC489529
0.52 Remote Similarity NPC263753
0.5167 Remote Similarity NPC62867
0.5167 Remote Similarity NPC177962
0.5098 Remote Similarity NPC102384
0.5098 Remote Similarity NPC99836
0.5091 Remote Similarity NPC68260
0.5091 Remote Similarity NPC85342
0.5091 Remote Similarity NPC206207
0.5091 Remote Similarity NPC279887
0.5085 Remote Similarity NPC116513
0.5085 Remote Similarity NPC197513

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC152097 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