Natural Product: NPC116934

Natural Product IDNPC116934
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 16-Hydroxygeranylgeraniol
IUPAC Name (2E,6E,10E,14E)-2,6,10,14-tetramethylhexadeca-2,6,10,14-tetraene-1,16-diol
Synonyms 16-Hydroxygeranylgeraniol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL471477
PubChem CID 11243710
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001551] Diterpenoids
          • [CHEMONTID:0001357] Acyclic diterpenoids

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 CLOPQFCHWDTGFD-BMTMAWCHSA-N
Standard InCHI InChI=1S/C20H34O2/c1-17(10-6-12-19(3)14-15-21)8-5-9-18(2)11-7-13-20(4)16-22/h9-10,13-14,21-22H,5-8,11-12,15-16H2,1-4H3/b17-10+,18-9+,19-14+,20-13+
SMILES C/C(=CCC/C(=C/CO)/C)/CC/C=C(C)/CC/C=C(C)/CO

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   306.26 Volume:   361.511
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Van der Waals volume.
Dense:   0.847 LogP:   5.693
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.591
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.548
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The logarithm of aqueous solubility value.
Rotatable Bonds:   11.0 Rigid Bonds:   4.0
TPSA:   40.46
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Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   2.0 Rings:   0.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.522 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.063 Fsp3:   0.6
MCE-18:   0.0
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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:   0.108 Fluc inhibitor:   0.0
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.0
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.002
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.788 Promiscuous compounds:   0.448

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.695 MDCK Permeability:   -4.861
Pgp-inhibitor:   1.0 Pgp-substrate:   0.0
PAMPA:   0.005
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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):   0.666
20% Bioavailability (F20%):   0.015 30% Bioavailability (F30%):   0.041
50% Bioavailability (F50%):   0.555

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.479
Plasma Protein Binding (PPB):   80.23% Volume Distribution (VD):   -0.311
Fu: 16.8%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.971

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.957 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.597 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.538 CYP2D6-substrate:   0.155
CYP3A4-inhibitor:   0.002 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.026
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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):  8.086 Half-life (T1/2):  1.053

ADMET: Toxicity

hERG Blockers:  0.044 hERG Blockers (10um):  0.242
Human Hepatotoxicity (H-HT):  0.886 Drug-induced Liver Injury (DILI):  0.019
AMES Toxicity:  0.079 Rat Oral Acute Toxicity:  0.011
Maximum Recommended Daily Dose:  0.042 Skin Sensitization:  0.997
Carcinogencity:  0.08 Eye Corrosion:  0.068
Eye Irritation:  0.985 Respiratory Toxicity:  0.939
Drug-induced Neurotoxicity:  0.267 Ototoxicity:  0.44
Hematotoxicity:  0.336 Drug-induced Nephrotoxicity:  0.571
Genotoxicity:  0.032 RPMI-8226 Immunitoxicity:  0.052
A549 Cytotoxicity:  0.068 Hek293 Cytotoxicity:  0.094
BCF:   2.248
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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:   5.048
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.317
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.788
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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
NPO28298 Boletinus cavipes Species Gyrodontaceae Eukaryota n.a. n.a. n.a. PMID[15217273]
NPO28298 Boletinus cavipes Species Gyrodontaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28298 Boletinus cavipes Species Gyrodontaceae 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
NPT967 Individual protein Xanthine dehydrogenase Homo sapiens Inhibition = 1.0 % PMID[8759172]
NPT967 Individual protein Xanthine dehydrogenase Homo sapiens Inhibition = 9.0 % PMID[23350742]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Inhibition = 84.0 % PubChem BioAssay data set

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 NPC116934 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
0.7692 Intermediate Similarity NPC29091
0.7692 Intermediate Similarity NPC103213
0.7692 Intermediate Similarity NPC300623
0.7692 Intermediate Similarity NPC213538
0.7692 Intermediate Similarity NPC269823
0.7692 Intermediate Similarity NPC39222
0.7692 Intermediate Similarity NPC9860
0.7059 Intermediate Similarity NPC474495
0.7059 Intermediate Similarity NPC473672
0.7 Intermediate Similarity NPC140501
0.6923 Remote Similarity NPC182840
0.6923 Remote Similarity NPC255042
0.6667 Remote Similarity NPC160628
0.6452 Remote Similarity NPC267110
0.6364 Remote Similarity NPC474496
0.6216 Remote Similarity NPC474460
0.6061 Remote Similarity NPC604226
0.5882 Remote Similarity NPC138935
0.5429 Remote Similarity NPC601961
0.5263 Remote Similarity NPC122239
0.5143 Remote Similarity NPC244038

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC116934 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
0.7 Intermediate Similarity NPD4265 Phase 2

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