Natural Product: NPC269823

Natural Product IDNPC269823
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Geranylgeraniol
IUPAC Name (2E,6E,10E)-3,7,11,15-tetramethylhexadeca-2,6,10,14-tetraen-1-ol
Synonyms Geranylgeraniol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL478589
PubChem CID 5281365
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 OJISWRZIEWCUBN-QIRCYJPOSA-N
Standard InCHI InChI=1S/C20H34O/c1-17(2)9-6-10-18(3)11-7-12-19(4)13-8-14-20(5)15-16-21/h9,11,13,15,21H,6-8,10,12,14,16H2,1-5H3/b18-11+,19-13+,20-15+
SMILES OC/C=C(/CC/C=C(/CC/C=C(/CCC=C(C)C)C)C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   290.26 Volume:   352.721
?
Van der Waals volume.
Dense:   0.823 LogP:   6.957
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.123
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.527
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   10.0 Rigid Bonds:   4.0
TPSA:   20.23
?
Topological Polar Surface Area.
 H-Bond Acceptor:   1.0
H-Bond Donor:   1.0 Rings:   0.0
Heavy Atoms:   1.0

MedChem Properties

QED Drug-Likeness Score:   0.48 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.952 Fsp3:   0.6
MCE-18:   0.0
?
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:   0.395 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.001
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.002
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.967 Promiscuous compounds:   0.111

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.488 MDCK Permeability:   -4.831
Pgp-inhibitor:   1.0 Pgp-substrate:   0.0
PAMPA:   0.001
?
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):   0.196
20% Bioavailability (F20%):   0.003 30% Bioavailability (F30%):   0.013
50% Bioavailability (F50%):   0.526

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.908
Plasma Protein Binding (PPB):   87.957% Volume Distribution (VD):   -0.262
Fu: 9.883%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.006
CYP2C19-inhibitor:   0.997 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.824 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.978 CYP2D6-substrate:   0.85
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.034
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.104
HLM stability:   0.992
?
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):  9.833 Half-life (T1/2):  1.06

ADMET: Toxicity

hERG Blockers:  0.058 hERG Blockers (10um):  0.368
Human Hepatotoxicity (H-HT):  0.804 Drug-induced Liver Injury (DILI):  0.063
AMES Toxicity:  0.075 Rat Oral Acute Toxicity:  0.05
Maximum Recommended Daily Dose:  0.078 Skin Sensitization:  0.996
Carcinogencity:  0.173 Eye Corrosion:  0.335
Eye Irritation:  0.981 Respiratory Toxicity:  0.934
Drug-induced Neurotoxicity:  0.524 Ototoxicity:  0.376
Hematotoxicity:  0.404 Drug-induced Nephrotoxicity:  0.48
Genotoxicity:  0.02 RPMI-8226 Immunitoxicity:  0.06
A549 Cytotoxicity:  0.141 Hek293 Cytotoxicity:  0.081
BCF:   2.362
?
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:   5.27
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.661
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.515
?
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
NPO25114 Linum usitatissimum Species Linaceae Eukaryota Seeds n.a. DOI[10.1002/ejlt.201100207]
NPO25114 Linum usitatissimum Species Linaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s11746-997-0093-1]
NPO681 Mesua ferrea Species Calophyllaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0040-4020(01)83306-8]
NPO25114 Linum usitatissimum Species Linaceae Eukaryota Seeds n.a. DOI[10.5219/332]
NPO15538 Eucalyptus citriodora Species Myrtaceae Eukaryota Leaves the campus of Panjab University, Chandigarh, India PMID[16989303]
NPO13083 Toona ciliata Species Meliaceae Eukaryota n.a. n.a. n.a. PMID[19275174]
NPO30686 Citrus hystrix Species Rutaceae Eukaryota n.a. exocarp n.a. PMID[20964319]
NPO25114 Linum usitatissimum Species Linaceae Eukaryota n.a. n.a. n.a. PMID[22537213]
NPO13083 Toona ciliata Species Meliaceae Eukaryota n.a. n.a. n.a. PMID[22537362]
NPO25114 Linum usitatissimum Species Linaceae Eukaryota n.a. n.a. n.a. PMID[24417583]
NPO15538 Eucalyptus citriodora Species Myrtaceae Eukaryota Essential oil n.a. n.a. PMID[24641242]
NPO25114 Linum usitatissimum Species Linaceae Eukaryota Seeds n.a. n.a. PMID[26923696]
NPO41844 A new engineered strain of Escherichia coli [acrE mdtE mdtC cmr] Strain Enterobacteriaceae Bacteria n.a. n.a. n.a. PMID[30309591]
NPO13083 Toona ciliata Species Meliaceae Eukaryota n.a. n.a. n.a. PMID[31503490]
NPO54179 Magnolia sumatrana var. glauca Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[34328033]
NPO51584 Magnolia hypolampra Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[34328033]
NPO55789 Prunus ulmifolia Species Rosaceae Eukaryota n.a. n.a. n.a. PMID[36302154]
NPO18952 Sambucus nigra Species Adoxaceae Eukaryota n.a. n.a. n.a. PMID[36675004]
NPO62378 Cladostephus spongiosus Species Cladostephaceae Eukaryota n.a. n.a. n.a. PMID[37504946]
NPO18952 Sambucus nigra Species Adoxaceae Eukaryota n.a. n.a. n.a. PMID[37570937]
NPO18952 Sambucus nigra Species Adoxaceae Eukaryota n.a. n.a. n.a. PMID[37759401]
NPO30686 Citrus hystrix Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[38067483]
NPO681 Mesua ferrea Species Calophyllaceae Eukaryota n.a. n.a. n.a. PMID[39621736]
NPO51770 Garcinia indica Species Clusiaceae Eukaryota n.a. n.a. n.a. PMID[39680751]
NPO681 Mesua ferrea Species Calophyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25114 Linum usitatissimum Species Linaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18952 Sambucus nigra Species Adoxaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30686 Citrus hystrix Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO41844 A new engineered strain of Escherichia coli [acrE mdtE mdtC cmr] Strain Enterobacteriaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO13083 Toona ciliata Species Meliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30541 Unum usitatissimum n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO51770 Garcinia indica Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25114 Linum usitatissimum Species Linaceae Eukaryota Seed Oil n.a. n.a. Database[FooDB]
NPO25114 Linum usitatissimum Species Linaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO18952 Sambucus nigra Species Adoxaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO18952 Sambucus nigra Species Adoxaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO25114 Linum usitatissimum Species Linaceae Eukaryota n.a. n.a. Database[FooDB]
NPO18952 Sambucus nigra Species Adoxaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO18952 Sambucus nigra Species Adoxaceae Eukaryota Flower n.a. n.a. Database[FooDB]
NPO25114 Linum usitatissimum Species Linaceae Eukaryota n.a. n.a. Database[FooDB]
NPO18952 Sambucus nigra Species Adoxaceae Eukaryota n.a. n.a. Database[FooDB]
NPO681 Mesua ferrea Species Calophyllaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO25114 Linum usitatissimum Species Linaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13083 Toona ciliata Species Meliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18952 Sambucus nigra Species Adoxaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18952 Sambucus nigra Species Adoxaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO681 Mesua ferrea Species Calophyllaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25114 Linum usitatissimum Species Linaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13083 Toona ciliata Species Meliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15538 Eucalyptus citriodora Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13083 Toona ciliata Species Meliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO30541 Unum usitatissimum n.a. n.a. n.a. n.a. n.a. n.a. Database[TCM_Taiwan]
NPO25114 Linum usitatissimum Species Linaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO25114 Linum usitatissimum Species Linaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13083 Toona ciliata Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18952 Sambucus nigra Species Adoxaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15538 Eucalyptus citriodora Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO681 Mesua ferrea Species Calophyllaceae 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
NPO18952 Sambucus nigra Oil Flowers 0.1 n.a. n.a. % PMID[37759401]
NPO30686 Citrus hystrix CO2 extract n.a. 0.31 n.a. n.a. % PMID[38067483]
NPO30686 Citrus hystrix Oil n.a. 0.79 n.a. n.a. % PMID[38067483]
NPO30686 Citrus hystrix Oil n.a. 0.64 n.a. n.a. % PMID[38067483]
NPO30686 Citrus hystrix CO2 extract n.a. 0.19 n.a. n.a. % PMID[38067483]
NPO51584 Magnolia hypolampra Oil Bark 0.26 n.a. n.a. % PMID[34328033]
NPO51770 Garcinia indica Ethanolic extract Fruits 0.76 n.a. n.a. % PMID[39680751]
NPO54179 Magnolia sumatrana var. glauca Oil Roots 0.26 n.a. n.a. % PMID[34328033]
NPO55789 Prunus ulmifolia Oil Leaves 0.21 n.a. n.a. % PMID[36302154]
NPO62378 Cladostephus spongiosus Hydro distillation n.a. 1.4 n.a. n.a. % PMID[37504946]
NPO62378 Cladostephus spongiosus Hydro distillation n.a. 1.79 n.a. n.a. % PMID[37504946]
NPO62378 Cladostephus spongiosus Hydro distillation n.a. 3.23 n.a. n.a. % PMID[37504946]
NPO62378 Cladostephus spongiosus Hydro distillation n.a. 2.84 n.a. n.a. % PMID[37504946]
NPO62378 Cladostephus spongiosus Hydro distillation n.a. 5.08 n.a. n.a. % PMID[37504946]
NPO62378 Cladostephus spongiosus Hydro distillation n.a. 6.77 n.a. n.a. % PMID[37504946]
NPO62378 Cladostephus spongiosus Hydro distillation n.a. 2.79 n.a. n.a. % PMID[37504946]
NPO62378 Cladostephus spongiosus Hydro distillation n.a. 3.88 n.a. n.a. % PMID[37504946]
NPO681 Mesua ferrea Ethanolic extract Branches 0.49 n.a. n.a. % PMID[39621736]

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
NPT531 Individual protein Nuclear receptor ROR-gamma Mus musculus Potency = 6309.6 nM PubChem BioAssay data set
NPT94 Individual protein Aldehyde dehydrogenase 1A1 Homo sapiens Potency = 2511.9 nM PubChem BioAssay data set
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 15848.9 nM PubChem BioAssay data set
NPT5 Individual protein Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 Homo sapiens Potency n.a. 25118.9 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT389 Cell line RPMI-8226 Homo sapiens Activity = 87.4 % PMID[30016091]
NPT389 Cell line RPMI-8226 Homo sapiens Activity = 4.71 % PMID[30016091]
NPT389 Cell line RPMI-8226 Homo sapiens Activity = 4.96 % PMID[30016091]
NPT389 Cell line RPMI-8226 Homo sapiens Activity = 2.91 % PMID[30016091]
NPT28438 Unchecked Unchecked n.a. Activity = 9.3 umol/mg/min PMID[33310291]

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 NPC269823 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
1.0 High Similarity NPC29091
1.0 High Similarity NPC103213
1.0 High Similarity NPC300623
1.0 High Similarity NPC213538
1.0 High Similarity NPC39222
1.0 High Similarity NPC9860
0.9091 High Similarity NPC182840
0.9091 High Similarity NPC255042
0.8148 Intermediate Similarity NPC140501
0.7692 Intermediate Similarity NPC116934
0.7 Intermediate Similarity NPC604226
0.6774 Remote Similarity NPC138935
0.6774 Remote Similarity NPC601961
0.6522 Remote Similarity NPC123965
0.6522 Remote Similarity NPC115959
0.625 Remote Similarity NPC474496
0.6 Remote Similarity NPC122239
0.5926 Remote Similarity NPC160628
0.5667 Remote Similarity NPC67761
0.5667 Remote Similarity NPC209279
0.5667 Remote Similarity NPC194586
0.5667 Remote Similarity NPC108494
0.5667 Remote Similarity NPC51758
0.5556 Remote Similarity NPC474495
0.5556 Remote Similarity NPC305759
0.5556 Remote Similarity NPC473672
0.5333 Remote Similarity NPC128280
0.5172 Remote Similarity NPC185839
0.5172 Remote Similarity NPC180840

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC269823 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
0.8148 Intermediate Similarity NPD4265 Phase 2
0.5172 Remote Similarity NPD5783 Phase 3

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