Natural Product: NPC310830

Natural Product IDNPC310830
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Floribundic Ester
IUPAC Name methyl (2S,4aS,6aR,10aS,10bS)-2-(furan-3-yl)-6a,10b-dimethyl-4-oxo-1,2,4a,5,6,9,10,10a-octahydrobenzo[f]isochromene-7-carboxylate
Synonyms Floribundic Ester
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL483178
PubChem CID 25110692
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones
          • [CHEMONTID:0001538] Diterpene 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 CCRPRTUMLVVFRR-BPERIUBUSA-N
Standard InCHI InChI=1S/C21H26O5/c1-20-9-7-15-19(23)26-16(13-8-10-25-12-13)11-21(15,2)17(20)6-4-5-14(20)18(22)24-3/h5,8,10,12,15-17H,4,6-7,9,11H2,1-3H3/t15-,16+,17-,20+,21-/m1/s1
SMILES C[C@]12CC[C@@H]3C(=O)O[C@@H](C[C@@]3(C)[C@@H]2CCC=C1C(=O)OC)c1ccoc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   358.18 Volume:   368.315
?
Van der Waals volume.
Dense:   0.972 LogP:   2.603
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.718
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.66
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   23.0
TPSA:   65.74
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.741 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.422 Fsp3:   0.619
MCE-18:   89.706
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.339 Fluc inhibitor:   0.334
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.017
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.006
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.265 Promiscuous compounds:   0.063

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.717 MDCK Permeability:   -4.595
Pgp-inhibitor:   0.105 Pgp-substrate:   0.011
PAMPA:   0.277
?
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):   0.002
20% Bioavailability (F20%):   0.078 30% Bioavailability (F30%):   0.104
50% Bioavailability (F50%):   0.604

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.409 MRP1:   0.596
Plasma Protein Binding (PPB):   84.647% Volume Distribution (VD):   0.189
Fu: 11.669%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.973
OATP1B3 inhibitor:   0.991 BCRP inhibitor:   0.414
BSEP inhibitor:   0.904

ADMET: Metabolism

CYP1A2-inhibitor:   0.003 CYP1A2-substrate:   0.936
CYP2C19-inhibitor:   0.052 CYP2C19-substrate:   0.274
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.023
CYP2D6-inhibitor:   0.002 CYP2D6-substrate:   0.691
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.994
HLM stability:   0.951
?
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):  7.734 Half-life (T1/2):  1.553

ADMET: Toxicity

hERG Blockers:  0.113 hERG Blockers (10um):  0.264
Human Hepatotoxicity (H-HT):  0.374 Drug-induced Liver Injury (DILI):  0.822
AMES Toxicity:  0.27 Rat Oral Acute Toxicity:  0.328
Maximum Recommended Daily Dose:  0.864 Skin Sensitization:  0.726
Carcinogencity:  0.806 Eye Corrosion:  0.087
Eye Irritation:  0.963 Respiratory Toxicity:  0.353
Drug-induced Neurotoxicity:  0.086 Ototoxicity:  0.191
Hematotoxicity:  0.107 Drug-induced Nephrotoxicity:  0.643
Genotoxicity:  0.695 RPMI-8226 Immunitoxicity:  0.029
A549 Cytotoxicity:  0.058 Hek293 Cytotoxicity:  0.111
BCF:   1.757
?
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:   4.306
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.3
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.668
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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
NPO10715 Fibraurea tinctoria Species Menispermaceae Eukaryota n.a. n.a. n.a. PMID[17994701]
NPO10715 Fibraurea tinctoria Species Menispermaceae Eukaryota n.a. n.a. n.a. PMID[18829331]
NPO10715 Fibraurea tinctoria Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10715 Fibraurea tinctoria Species Menispermaceae 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

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus Activity = 13.07 % DrugMatrix in vitro pharmacology data
NPT32 Organism Mus musculus Mus musculus Activity = 14.9 % PubChem BioAssay data set
NPT32 Organism Mus musculus Mus musculus Activity = 13.95 % PMID[9917306]
NPT32 Organism Mus musculus Mus musculus Activity = 16.78 % PMID[9917306]
NPT32 Organism Mus musculus Mus musculus Activity = 15.46 % PubChem BioAssay data set
NPT32 Organism Mus musculus Mus musculus Activity = 20.18 % PMID[18299197]
NPT32 Organism Mus musculus Mus musculus Activity = 21.85 % PMID[18299197]
NPT32 Organism Mus musculus Mus musculus Activity = 21.84 % PMID[18299197]
NPT32 Organism Mus musculus Mus musculus Activity = 21.51 % PMID[18299197]
NPT32 Organism Mus musculus Mus musculus Activity = 20.95 % PMID[18299197]
NPT32 Organism Mus musculus Mus musculus Activity = 16.27 % PMID[18093835]





 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 NPC310830 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
0.8033 Intermediate Similarity NPC606229
0.6528 Remote Similarity NPC610593
0.6377 Remote Similarity NPC476944
0.6351 Remote Similarity NPC606944
0.6351 Remote Similarity NPC610061
0.6173 Remote Similarity NPC211777
0.6173 Remote Similarity NPC605767
0.6029 Remote Similarity NPC289537
0.5882 Remote Similarity NPC476943
0.56 Remote Similarity NPC303842
0.5556 Remote Similarity NPC608381
0.5556 Remote Similarity NPC609872
0.5479 Remote Similarity NPC600426
0.5479 Remote Similarity NPC601789
0.5412 Remote Similarity NPC198047
0.5412 Remote Similarity NPC608617
0.5402 Remote Similarity NPC606610
0.5385 Remote Similarity NPC476941
0.5385 Remote Similarity NPC476942
0.5349 Remote Similarity NPC486155
0.5349 Remote Similarity NPC606206
0.5333 Remote Similarity NPC262198
0.5333 Remote Similarity NPC485313
0.5062 Remote Similarity NPC476938
0.5062 Remote Similarity NPC476937

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC310830 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