Natural Product: NPC274704

Natural Product IDNPC274704
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Isopachydictyol A
IUPAC Name (3aS,4R,5S,8aR)-3,8-dimethyl-5-[(2R)-6-methylhept-5-en-2-yl]-1,3a,4,5,6,8a-hexahydroazulen-4-ol
Synonyms Isopachydictyol A
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1652217
PubChem CID 21583475
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001551] Diterpenoids
          • [CHEMONTID:0003550] Pachydictyane and cneorubin 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 QHFVETGCBIHSLB-RBUQIHAASA-N
Standard InCHI InChI=1S/C20H32O/c1-13(2)7-6-8-14(3)18-12-9-15(4)17-11-10-16(5)19(17)20(18)21/h7,9-10,14,17-21H,6,8,11-12H2,1-5H3/t14-,17+,18+,19-,20-/m1/s1
SMILES CC(=CCC[C@@H](C)[C@@H]1CC=C(C)[C@@H]2CC=C(C)[C@H]2[C@@H]1O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   288.25 Volume:   338.244
?
Van der Waals volume.
Dense:   0.852 LogP:   4.807
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.681
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.24
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   12.0
TPSA:   20.23
?
Topological Polar Surface Area.
 H-Bond Acceptor:   1.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   1.0

MedChem Properties

QED Drug-Likeness Score:   0.698 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.435 Fsp3:   0.7
MCE-18:   32.941
?
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:   0.826 Fluc inhibitor:   0.003
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.031
?
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:   0.862 Promiscuous compounds:   0.243

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.075 MDCK Permeability:   -4.785
Pgp-inhibitor:   0.721 Pgp-substrate:   0.101
PAMPA:   0.234
?
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):   0.018
20% Bioavailability (F20%):   0.25 30% Bioavailability (F30%):   0.776
50% Bioavailability (F50%):   0.975

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.05 MRP1:   0.824
Plasma Protein Binding (PPB):   93.913% Volume Distribution (VD):   0.238
Fu: 7.649%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.963 BCRP inhibitor:   0.047
BSEP inhibitor:   0.461

ADMET: Metabolism

CYP1A2-inhibitor:   0.017 CYP1A2-substrate:   0.652
CYP2C19-inhibitor:   0.541 CYP2C19-substrate:   0.14
CYP2C9-inhibitor:   0.022 CYP2C9-substrate:   0.026
CYP2D6-inhibitor:   0.059 CYP2D6-substrate:   0.132
CYP3A4-inhibitor:   0.954 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.596
HLM stability:   0.884
?
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):  11.962 Half-life (T1/2):  0.882

ADMET: Toxicity

hERG Blockers:  0.042 hERG Blockers (10um):  0.273
Human Hepatotoxicity (H-HT):  0.531 Drug-induced Liver Injury (DILI):  0.392
AMES Toxicity:  0.184 Rat Oral Acute Toxicity:  0.262
Maximum Recommended Daily Dose:  0.056 Skin Sensitization:  0.971
Carcinogencity:  0.501 Eye Corrosion:  0.84
Eye Irritation:  0.959 Respiratory Toxicity:  0.333
Drug-induced Neurotoxicity:  0.323 Ototoxicity:  0.361
Hematotoxicity:  0.601 Drug-induced Nephrotoxicity:  0.449
Genotoxicity:  0.244 RPMI-8226 Immunitoxicity:  0.046
A549 Cytotoxicity:  0.196 Hek293 Cytotoxicity:  0.068
BCF:   2.904
?
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:   4.534
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.237
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.321
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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
NPO6812 Bulbine frutescens Species Xanthorrhoeaceae Eukaryota n.a. root n.a. PMID[12193014]
NPO32968 dictoyota dichotoma Species n.a. n.a. n.a. n.a. n.a. PMID[21130542]
NPO8948 Streptomyces pristinaespiralis Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[25708513]
NPO8796 Cnemidocarpa bicornuta Species Styelidae Eukaryota n.a. New Zealand n.a. PMID[9644087]
NPO6812 Bulbine frutescens Species Xanthorrhoeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1481 Balfourodendron riedelianum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8948 Streptomyces pristinaespiralis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO29285 Dendrobium densiflorum Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29313 Halomonas meridiana Species Halomonadaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO29308 Mycobacterium marinum Species Mycobacteriaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO29146 Polygonatum kingianum Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8033 Sordaria macrospora Species Sordariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8796 Cnemidocarpa bicornuta Species Styelidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO604 Erysimum crepidifolium Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12335 Aristolochia reticulata Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO604 Erysimum crepidifolium Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29285 Dendrobium densiflorum Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO604 Erysimum crepidifolium Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29146 Polygonatum kingianum Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29285 Dendrobium densiflorum Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29146 Polygonatum kingianum Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29146 Polygonatum kingianum Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO8948 Streptomyces pristinaespiralis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO29308 Mycobacterium marinum Species Mycobacteriaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO6812 Bulbine frutescens Species Xanthorrhoeaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29313 Halomonas meridiana Species Halomonadaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO7039 Espeletia uribei Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29146 Polygonatum kingianum Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5863 Amyris plumieri Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12648 Uragoga ipecacuanha n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO2958 Euphorbia glareosa Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9742 Entada scandens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8033 Sordaria macrospora Species Sordariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO604 Erysimum crepidifolium Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26935 Coprinopsis lagopus Species Psathyrellaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29285 Dendrobium densiflorum Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1481 Balfourodendron riedelianum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16389 Anodonta cygnea Species Unionidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12335 Aristolochia reticulata Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8796 Cnemidocarpa bicornuta Species Styelidae 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
NPT65 Cell line HepG2 Homo sapiens IC50 = 39.2 ug.mL-1 PMID[21130542]
NPT189 Cell line Vero Chlorocebus aethiops IC50 = 28.3 ug.mL-1 PMID[21130542]
NPT83 Cell line MCF7 Homo sapiens IC50 = 39.2 ug.mL-1 PMID[21130542]
NPT632 Tissue Brain Rattus norvegicus Inhibition = 59.9 % PMID[21130542]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 48.4 % PMID[21130542]

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 NPC274704 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
0.7073 Intermediate Similarity NPC279200
0.5909 Remote Similarity NPC272125
0.5909 Remote Similarity NPC74548
0.5909 Remote Similarity NPC603793
0.54 Remote Similarity NPC600093
0.5122 Remote Similarity NPC326310

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC274704 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