Natural Product: NPC477302

Natural Product IDNPC477302
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 6beta-O-(2-methylbutyryl)britannilactone
IUPAC Name [(3aR,4R,7aR)-5-[(2S)-5-hydroxypentan-2-yl]-6-methyl-3-methylidene-2-oxo-3a,4,7,7a-tetrahydro-1-benzofuran-4-yl] 2-methylbutanoate
Synonyms 6beta-O-(2-methylbutyryl)britannilactone
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11638861
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones

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 SVXWZIOAARZZFZ-XKIUHSEASA-N
Standard InCHI InChI=1S/C20H30O5/c1-6-11(2)19(22)25-18-16(12(3)8-7-9-21)13(4)10-15-17(18)14(5)20(23)24-15/h11-12,15,17-18,21H,5-10H2,1-4H3/t11?,12-,15+,17+,18-/m0/s1
SMILES CCC(C)C(=O)O[C@@H]1[C@H]2[C@@H](CC(=C1[C@@H](C)CCCO)C)OC(=O)C2=C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   350.21 Volume:   370.769
?
Van der Waals volume.
Dense:   0.945 LogP:   3.37
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.098
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.048
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The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   13.0
TPSA:   72.83
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Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.434 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.515 Fsp3:   0.7
MCE-18:   35.765
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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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.395 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:   0.059
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.02
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.433 Promiscuous compounds:   0.154

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.921 MDCK Permeability:   -4.618
Pgp-inhibitor:   0.057 Pgp-substrate:   0.779
PAMPA:   0.458
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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):   0.0
20% Bioavailability (F20%):   0.45 30% Bioavailability (F30%):   0.912
50% Bioavailability (F50%):   0.973

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.226 MRP1:   0.997
Plasma Protein Binding (PPB):   69.233% Volume Distribution (VD):   -0.063
Fu: 29.196%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.953
OATP1B3 inhibitor:   0.845 BCRP inhibitor:   0.001
BSEP inhibitor:   0.987

ADMET: Metabolism

CYP1A2-inhibitor:   0.034 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.307 CYP2C19-substrate:   0.004
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.385
CYP3A4-inhibitor:   0.788 CYP3A4-substrate:   0.883
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.998
HLM stability:   0.87
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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):  8.129 Half-life (T1/2):  0.99

ADMET: Toxicity

hERG Blockers:  0.033 hERG Blockers (10um):  0.279
Human Hepatotoxicity (H-HT):  0.762 Drug-induced Liver Injury (DILI):  0.856
AMES Toxicity:  0.767 Rat Oral Acute Toxicity:  0.3
Maximum Recommended Daily Dose:  0.227 Skin Sensitization:  0.999
Carcinogencity:  0.731 Eye Corrosion:  0.565
Eye Irritation:  0.897 Respiratory Toxicity:  0.352
Drug-induced Neurotoxicity:  0.791 Ototoxicity:  0.516
Hematotoxicity:  0.889 Drug-induced Nephrotoxicity:  0.96
Genotoxicity:  0.456 RPMI-8226 Immunitoxicity:  0.25
A549 Cytotoxicity:  0.344 Hek293 Cytotoxicity:  0.353
BCF:   0.844
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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:   3.511
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.139
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.424
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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
NPO17782 Inula britannica Species Asteraceae Eukaryota flowers n.a. n.a. PMID[16643020]
NPO17782 Inula britannica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17782 Inula britannica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17782 Inula britannica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17782 Inula britannica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO17782 Inula britannica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO17782 Inula britannica Species Asteraceae 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
NPT407 Cell line COLO 205 Homo sapiens IC50 = 58700 nM PMID[16643020]
NPT139 Cell line HT-29 Homo sapiens IC50 = 48100 nM PMID[16643020]
NPT116 Cell line HL-60 Homo sapiens IC50 = 47100 nM PMID[16643020]
NPT196 Cell line AGS Homo sapiens IC50 = 31300 nM PMID[16643020]
NPT407 Cell line COLO 205 Homo sapiens Activity = 5.33 % PMID[16643020]
NPT407 Cell line COLO 205 Homo sapiens Activity = 5.86 % PMID[16643020]
NPT407 Cell line COLO 205 Homo sapiens Activity = 15.2 % PMID[16643020]
NPT407 Cell line COLO 205 Homo sapiens Activity = 27.21 % PMID[16643020]
NPT407 Cell line COLO 205 Homo sapiens Activity = 36.24 % PMID[16643020]
NPT139 Cell line HT-29 Homo sapiens Activity = 4.24 % PMID[16643020]
NPT139 Cell line HT-29 Homo sapiens Activity = 3.68 % PMID[16643020]
NPT139 Cell line HT-29 Homo sapiens Activity = 3.93 % PMID[16643020]
NPT139 Cell line HT-29 Homo sapiens Activity = 5.16 % PMID[16643020]
NPT139 Cell line HT-29 Homo sapiens Activity = 6.4 % PMID[16643020]
NPT116 Cell line HL-60 Homo sapiens Activity = 6.41 % PMID[16643020]
NPT116 Cell line HL-60 Homo sapiens Activity = 5.36 % PMID[16643020]
NPT116 Cell line HL-60 Homo sapiens Activity = 10.53 % PMID[16643020]
NPT116 Cell line HL-60 Homo sapiens Activity = 28.6 % PMID[16643020]
NPT116 Cell line HL-60 Homo sapiens Activity = 27.05 % PMID[16643020]
NPT196 Cell line AGS Homo sapiens Activity = 10.89 % PMID[16643020]
NPT196 Cell line AGS Homo sapiens Activity = 11.38 % PMID[16643020]
NPT196 Cell line AGS Homo sapiens Activity = 17.76 % PMID[16643020]
NPT196 Cell line AGS Homo sapiens Activity = 28.48 % PMID[16643020]
NPT196 Cell line AGS Homo sapiens Activity = 27.1 % PMID[16643020]

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 NPC477302 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
0.6667 Remote Similarity NPC607318
0.6111 Remote Similarity NPC159635
0.5763 Remote Similarity NPC483169
0.5179 Remote Similarity NPC136879

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC477302 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