Natural Product: NPC477685

Natural Product IDNPC477685
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2-methyl-5-[(2Z,6Z)-3,7,11-trimethyldodeca-2,6,10-trienyl]benzene-1,4-diol
IUPAC Name 2-methyl-5-[(2Z,6Z)-3,7,11-trimethyldodeca-2,6,10-trienyl]benzene-1,4-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 44566895
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001550] Sesquiterpenoids

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 WMICYZWXGIMHIB-NGEVDRGDSA-N
Standard InCHI InChI=1S/C22H32O2/c1-16(2)8-6-9-17(3)10-7-11-18(4)12-13-20-15-21(23)19(5)14-22(20)24/h8,10,12,14-15,23-24H,6-7,9,11,13H2,1-5H3/b17-10-,18-12-
SMILES CC1=CC(=C(C=C1O)C/C=C(/C)\CC/C=C(/C)\CCC=C(C)C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   328.24 Volume:   382.273
?
Van der Waals volume.
Dense:   0.859 LogP:   7.586
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.356
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.808
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The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   9.0
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:   0.43 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.878 Fsp3:   0.455
MCE-18:   10.0
?
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:   0.741 Fluc inhibitor:   0.103
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.007
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.088
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.777 Promiscuous compounds:   0.065

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.813 MDCK Permeability:   -4.729
Pgp-inhibitor:   0.935 Pgp-substrate:   0.002
PAMPA:   0.004
?
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):   0.003
20% Bioavailability (F20%):   0.914 30% Bioavailability (F30%):   0.971
50% Bioavailability (F50%):   0.989

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.052 MRP1:   0.996
Plasma Protein Binding (PPB):   97.003% Volume Distribution (VD):   0.338
Fu: 3.52%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.608
OATP1B3 inhibitor:   0.875 BCRP inhibitor:   0.375
BSEP inhibitor:   0.996

ADMET: Metabolism

CYP1A2-inhibitor:   0.226 CYP1A2-substrate:   0.994
CYP2C19-inhibitor:   0.98 CYP2C19-substrate:   0.834
CYP2C9-inhibitor:   0.943 CYP2C9-substrate:   0.05
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.946
CYP3A4-inhibitor:   0.009 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.982
?
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):  11.474 Half-life (T1/2):  1.082

ADMET: Toxicity

hERG Blockers:  0.101 hERG Blockers (10um):  0.67
Human Hepatotoxicity (H-HT):  0.431 Drug-induced Liver Injury (DILI):  0.015
AMES Toxicity:  0.162 Rat Oral Acute Toxicity:  0.072
Maximum Recommended Daily Dose:  0.316 Skin Sensitization:  0.999
Carcinogencity:  0.187 Eye Corrosion:  0.465
Eye Irritation:  0.989 Respiratory Toxicity:  0.806
Drug-induced Neurotoxicity:  0.379 Ototoxicity:  0.294
Hematotoxicity:  0.116 Drug-induced Nephrotoxicity:  0.21
Genotoxicity:  0.006 RPMI-8226 Immunitoxicity:  0.036
A549 Cytotoxicity:  0.22 Hek293 Cytotoxicity:  0.157
BCF:   2.367
?
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:   5.691
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.702
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.515
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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
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[10479323]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[12350167]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[14640527]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota Axinella verrucosa Mediterranean n.a. PMID[14738391]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[15043411]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. Sussex Inlet, New South Wales, Australia n.a. PMID[15104517]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[15332862]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. Berkeley Pit lake n.a. PMID[17970594]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. New Zealand n.a. PMID[19323568]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[19326880]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[20452770]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. North Sea n.a. PMID[21126094]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21126094]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. Limonium tubiflorum n.a. PMID[21146414]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21916432]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[22148349]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[22458669]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[23360521]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[23477451]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[23603293]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[23972215]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[24033077]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[24437979]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[31433188]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[9392888]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT81 Cell line A549 Homo sapiens ED50 = 4.73 ug/ml PMID[14640527]
NPT146 Cell line SK-OV-3 Homo sapiens ED50 = 5.31 ug/ml PMID[14640527]
NPT147 Cell line SK-MEL-2 Homo sapiens ED50 = 4.8 ug/ml PMID[14640527]
NPT574 Cell line XF498 Homo sapiens ED50 = 5.94 ug/ml PMID[14640527]
NPT148 Cell line HCT-15 Homo sapiens ED50 = 6.11 ug/ml PMID[14640527]

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 NPC477685 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
0.75 Intermediate Similarity NPC484189
0.7 Intermediate Similarity NPC95305
0.6889 Remote Similarity NPC260775
0.6889 Remote Similarity NPC130756
0.6889 Remote Similarity NPC70677
0.6889 Remote Similarity NPC12931
0.6444 Remote Similarity NPC12640
0.6444 Remote Similarity NPC152097
0.6182 Remote Similarity NPC265793
0.6042 Remote Similarity NPC76400
0.56 Remote Similarity NPC263753
0.549 Remote Similarity NPC99836
0.5385 Remote Similarity NPC606098
0.5273 Remote Similarity NPC474890
0.5273 Remote Similarity NPC273282
0.5263 Remote Similarity NPC282855
0.5263 Remote Similarity NPC26013
0.5192 Remote Similarity NPC98392
0.5185 Remote Similarity NPC80800
0.5179 Remote Similarity NPC180261
0.5098 Remote Similarity NPC201662
0.5091 Remote Similarity NPC483761
0.5091 Remote Similarity NPC166995
0.5088 Remote Similarity NPC155072

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC477685 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