Natural Product: NPC176621

Natural Product IDNPC176621
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Fuscol
IUPAC Name (3E,5E)-6-[(1S,3R,4R)-4-ethenyl-4-methyl-3-prop-1-en-2-ylcyclohexyl]-2-methylhepta-3,5-dien-2-ol
Synonyms Fuscol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL476288
PubChem CID 10891538
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001551] 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 PGZCBHXBAUSEPY-VHSBKHBUSA-N
Standard InCHI InChI=1S/C20H32O/c1-8-20(7)13-11-17(14-18(20)15(2)3)16(4)10-9-12-19(5,6)21/h8-10,12,17-18,21H,1-2,11,13-14H2,3-7H3/b12-9+,16-10+/t17-,18+,20-/m0/s1
SMILES C=C[C@@]1(C)CC[C@@H](C[C@@H]1C(=C)C)/C(=C/C=C/C(C)(C)O)/C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   288.25 Volume:   344.164
?
Van der Waals volume.
Dense:   0.838 LogP:   3.479
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.282
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.959
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   10.0
TPSA:   20.23
?
Topological Polar Surface Area.
 H-Bond Acceptor:   1.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   1.0

MedChem Properties

QED Drug-Likeness Score:   0.527 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.482 Fsp3:   0.6
MCE-18:   30.875
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.393 Fluc inhibitor:   0.017
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.002
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.977 Promiscuous compounds:   0.38

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.531 MDCK Permeability:   -4.602
Pgp-inhibitor:   0.146 Pgp-substrate:   0.003
PAMPA:   0.194
?
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):   0.0
20% Bioavailability (F20%):   0.005 30% Bioavailability (F30%):   0.009
50% Bioavailability (F50%):   0.82

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.074 MRP1:   0.451
Plasma Protein Binding (PPB):   96.282% Volume Distribution (VD):   0.167
Fu: 3.316%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.945
OATP1B3 inhibitor:   0.783 BCRP inhibitor:   0.993
BSEP inhibitor:   0.989

ADMET: Metabolism

CYP1A2-inhibitor:   0.163 CYP1A2-substrate:   0.896
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.05
CYP2C9-inhibitor:   0.962 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.391 CYP2D6-substrate:   0.85
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.965
CYP2B6-substrate:   0.858 CYP2C8-inhibitor:   0.999
HLM stability:   0.804
?
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):  8.95 Half-life (T1/2):  0.461

ADMET: Toxicity

hERG Blockers:  0.099 hERG Blockers (10um):  0.436
Human Hepatotoxicity (H-HT):  0.62 Drug-induced Liver Injury (DILI):  0.258
AMES Toxicity:  0.354 Rat Oral Acute Toxicity:  0.591
Maximum Recommended Daily Dose:  0.787 Skin Sensitization:  0.871
Carcinogencity:  0.811 Eye Corrosion:  0.445
Eye Irritation:  0.979 Respiratory Toxicity:  0.969
Drug-induced Neurotoxicity:  0.408 Ototoxicity:  0.555
Hematotoxicity:  0.303 Drug-induced Nephrotoxicity:  0.303
Genotoxicity:  0.619 RPMI-8226 Immunitoxicity:  0.068
A549 Cytotoxicity:  0.502 Hek293 Cytotoxicity:  0.484
BCF:   2.066
?
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:   4.22
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.582
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.06
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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
NPO27691 Eunicea fusca Species Plexauridae Eukaryota n.a. Caribbean n.a. PMID[21865038]
NPO26994 Lobophytum pauciflorum Species Alcyoniidae Eukaryota n.a. n.a. n.a. PMID[22209732]
NPO27691 Eunicea fusca Species Plexauridae Eukaryota n.a. n.a. n.a. PMID[22734800]
NPO26994 Lobophytum pauciflorum Species Alcyoniidae Eukaryota n.a. Mindoro, Philippines n.a. PMID[9548875]
NPO26994 Lobophytum pauciflorum Species Alcyoniidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27691 Eunicea fusca Species Plexauridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27691 Eunicea fusca Species Plexauridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26994 Lobophytum pauciflorum Species Alcyoniidae 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
NPT762 Cell line A-431 Homo sapiens IC50 = 520.0 nM PMID[21421320]
NPT985 Organism Cladosporium cucumerinum Cladosporium cucumerinum IZ = 2.0 mm PMID[23199475]
NPT985 Organism Cladosporium cucumerinum Cladosporium cucumerinum IZ = 0.0 mm PMID[18198839]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus Inhibition = 27.3 % PMID[21982796]
NPT32 Organism Mus musculus Mus musculus Inhibition = 0.1 % PMID[2128517]
NPT32 Organism Mus musculus Mus musculus Activity = 46.0 % PMID[22292922]





 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
- Artemia salina LC50 = 4.18 ug.mL-1 PMID[25467159]

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 NPC176621 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
0.5952 Remote Similarity NPC250977
0.5882 Remote Similarity NPC190232
0.5882 Remote Similarity NPC105246
0.5532 Remote Similarity NPC488474
0.5526 Remote Similarity NPC39068
0.5366 Remote Similarity NPC124851
0.5319 Remote Similarity NPC469728
0.5102 Remote Similarity NPC104644

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC176621 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
0.5882 Remote Similarity NPD1799 Clinical (unspecified phase)

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