Natural Product: NPC304687

Natural Product IDNPC304687
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5-(3,4,5-Trimethoxyphenyl)-5A,8,8A,9-Tetrahydro-5H-[2]Benzofuro[5,6-F][1,3]Benzodioxol-6-One
IUPAC Name 5-(3,4,5-trimethoxyphenyl)-5a,8,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-6-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1736070
PubChem CID 2203
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0001510] Lignan 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 ZGLXUQQMLLIKAN-UHFFFAOYSA-N
Standard InCHI InChI=1S/C22H22O7/c1-24-17-6-12(7-18(25-2)21(17)26-3)19-14-8-16-15(28-10-29-16)5-11(14)4-13-9-27-22(23)20(13)19/h5-8,13,19-20H,4,9-10H2,1-3H3
SMILES COc1cc(cc(c1OC)OC)C1c2cc3c(cc2CC2COC(=O)C12)OCO3

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   398.14 Volume:   389.362
?
Van der Waals volume.
Dense:   1.023 LogP:   2.329
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.562
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.664
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   26.0
TPSA:   72.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   0.0 Rings:   5.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.733 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.554 Fsp3:   0.409
MCE-18:   91.452
?
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:   0.067 Fluc inhibitor:   0.002
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.122
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.332
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.095 Promiscuous compounds:   0.126

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.755 MDCK Permeability:   -4.676
Pgp-inhibitor:   0.059 Pgp-substrate:   0.001
PAMPA:   0.028
?
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%):   0.002 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.074

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.99 MRP1:   0.999
Plasma Protein Binding (PPB):   98.726% Volume Distribution (VD):   -0.226
Fu: 1.168%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.484
OATP1B3 inhibitor:   0.874 BCRP inhibitor:   0.001
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.121 CYP1A2-substrate:   0.957
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.997
CYP2C9-inhibitor:   0.322 CYP2C9-substrate:   0.174
CYP2D6-inhibitor:   0.002 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.989
CYP2B6-substrate:   0.584 CYP2C8-inhibitor:   0.373
HLM stability:   0.453
?
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):  3.679 Half-life (T1/2):  1.881

ADMET: Toxicity

hERG Blockers:  0.221 hERG Blockers (10um):  0.722
Human Hepatotoxicity (H-HT):  0.835 Drug-induced Liver Injury (DILI):  0.965
AMES Toxicity:  0.488 Rat Oral Acute Toxicity:  0.369
Maximum Recommended Daily Dose:  0.864 Skin Sensitization:  0.38
Carcinogencity:  0.935 Eye Corrosion:  0.0
Eye Irritation:  0.157 Respiratory Toxicity:  0.62
Drug-induced Neurotoxicity:  0.83 Ototoxicity:  0.899
Hematotoxicity:  0.628 Drug-induced Nephrotoxicity:  0.853
Genotoxicity:  0.75 RPMI-8226 Immunitoxicity:  0.159
A549 Cytotoxicity:  0.325 Hek293 Cytotoxicity:  0.517
BCF:   1.597
?
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:   4.096
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.508
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.212
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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
NPO13539 Thuja occidentalis Species Cupressaceae Eukaryota n.a. n.a. n.a. PMID[11000026]
NPO10903 Sinopodophyllum hexandrum Species Berberidaceae Eukaryota n.a. n.a. n.a. PMID[26359402]
NPO20275 Juniperus sabina Species Cupressaceae Eukaryota n.a. n.a. n.a. PMID[34203980]
NPO20275 Juniperus sabina Species Cupressaceae Eukaryota n.a. n.a. n.a. PMID[37894884]
NPO13539 Thuja occidentalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10903 Sinopodophyllum hexandrum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20275 Juniperus sabina Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13539 Thuja occidentalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20275 Juniperus sabina Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13539 Thuja occidentalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20275 Juniperus sabina Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO30053 Podophyllum emodll Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20275 Juniperus sabina Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10903 Sinopodophyllum hexandrum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO20275 Juniperus sabina Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10903 Sinopodophyllum hexandrum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13539 Thuja occidentalis Species Cupressaceae 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
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens Potency n.a. 23109.3 nM PubChem BioAssay data set
NPT154 Individual protein Mothers against decapentaplegic homolog 3 Homo sapiens Potency n.a. 15848.9 nM PubChem BioAssay data set
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 6513.1 nM PubChem BioAssay data set
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 1636.0 nM PubChem BioAssay data set
NPT101 Individual protein Glucagon-like peptide 1 receptor Homo sapiens Potency n.a. 281.8 nM PubChem BioAssay data set
NPT478 Individual protein Ataxin-2 Homo sapiens Potency n.a. 1122.0 nM PubChem BioAssay data set
NPT861 Individual protein Isocitrate dehydrogenase [NADP] cytoplasmic Homo sapiens Potency n.a. 366.3 nM PubChem BioAssay data set
NPT49 Individual protein DNA-(apurinic or apyrimidinic site) lyase Homo sapiens Potency n.a. 237.8 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Potency n.a. 10322.5 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. IC50 > 80000.0 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 316.2 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 354.8 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 8912.5 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 5804.8 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 231.1 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 28183.8 nM PubChem BioAssay data set

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 NPC304687 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
1.0 High Similarity NPC80230
1.0 High Similarity NPC104024
1.0 High Similarity NPC101755
1.0 High Similarity NPC65574
0.9423 High Similarity NPC262455
0.9423 High Similarity NPC177476
0.8 Intermediate Similarity NPC218092
0.8 Intermediate Similarity NPC246474
0.8 Intermediate Similarity NPC162851
0.7931 Intermediate Similarity NPC30009
0.7931 Intermediate Similarity NPC103197
0.7586 Intermediate Similarity NPC149505
0.7288 Intermediate Similarity NPC480477
0.6984 Remote Similarity NPC115281
0.6806 Remote Similarity NPC115624
0.65 Remote Similarity NPC239890
0.65 Remote Similarity NPC209411
0.619 Remote Similarity NPC237946
0.619 Remote Similarity NPC32373
0.6 Remote Similarity NPC210642
0.6 Remote Similarity NPC13985
0.5965 Remote Similarity NPC480480
0.5882 Remote Similarity NPC163527
0.5763 Remote Similarity NPC23336
0.5758 Remote Similarity NPC207584
0.5758 Remote Similarity NPC19947
0.5588 Remote Similarity NPC119910
0.557 Remote Similarity NPC222531
0.55 Remote Similarity NPC40237
0.5484 Remote Similarity NPC477698
0.5424 Remote Similarity NPC151423
0.5397 Remote Similarity NPC176586
0.5397 Remote Similarity NPC210354
0.5333 Remote Similarity NPC92693
0.5323 Remote Similarity NPC164082
0.5254 Remote Similarity NPC218841
0.5082 Remote Similarity NPC475000
0.5077 Remote Similarity NPC191158
0.5077 Remote Similarity NPC177644
0.507 Remote Similarity NPC288149
0.507 Remote Similarity NPC470637

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC304687 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
0.619 Remote Similarity NPD4965 Approved
0.619 Remote Similarity NPD4966 Phase 4
0.619 Remote Similarity NPD4967 Phase 2

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