Natural Product: NPC216223

Natural Product IDNPC216223
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (3S,4S)-3-[(4-Hydroxy-3-Methoxyphenyl)Methyl]-4-[(7-Methoxy-1,3-Benzodioxol-5-Yl)Methyl]Oxolan-2-One
IUPAC Name (3S,4S)-3-[(4-hydroxy-3-methoxyphenyl)methyl]-4-[(7-methoxy-1,3-benzodioxol-5-yl)methyl]oxolan-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL491365
PubChem CID 11429099
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid lignans
        • [CHEMONTID:0001604] Tetrahydrofuran lignans
          • [CHEMONTID:0003424] 9,9'-epoxylignans
            • [CHEMONTID:0001613] Dibenzylbutyrolactone lignans

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 FZFUSCRYZHVQNP-CABCVRRESA-N
Standard InCHI InChI=1S/C21H22O7/c1-24-17-7-12(3-4-16(17)22)6-15-14(10-26-21(15)23)5-13-8-18(25-2)20-19(9-13)27-11-28-20/h3-4,7-9,14-15,22H,5-6,10-11H2,1-2H3/t14-,15+/m1/s1
SMILES COc1cc(ccc1O)C[C@H]1[C@H](Cc2cc(c3c(c2)OCO3)OC)COC1=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   386.14 Volume:   380.623
?
Van der Waals volume.
Dense:   1.014 LogP:   2.076
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.329
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.643
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   22.0
TPSA:   83.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.764 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.351 Fsp3:   0.381
MCE-18:   72.069
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.264 Fluc inhibitor:   0.312
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.035
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.404
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.224 Promiscuous compounds:   0.246

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.917 MDCK Permeability:   -4.687
Pgp-inhibitor:   0.867 Pgp-substrate:   0.052
PAMPA:   0.012
?
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%):   0.706 30% Bioavailability (F30%):   0.203
50% Bioavailability (F50%):   0.885

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.776
Plasma Protein Binding (PPB):   97.837% Volume Distribution (VD):   -0.466
Fu: 2.308%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.024
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.682 CYP1A2-substrate:   0.988
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.694 CYP2C9-substrate:   0.987
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.998
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.905
?
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):  4.876 Half-life (T1/2):  1.333

ADMET: Toxicity

hERG Blockers:  0.268 hERG Blockers (10um):  0.622
Human Hepatotoxicity (H-HT):  0.936 Drug-induced Liver Injury (DILI):  0.981
AMES Toxicity:  0.672 Rat Oral Acute Toxicity:  0.662
Maximum Recommended Daily Dose:  0.762 Skin Sensitization:  0.978
Carcinogencity:  0.784 Eye Corrosion:  0.002
Eye Irritation:  0.857 Respiratory Toxicity:  0.675
Drug-induced Neurotoxicity:  0.899 Ototoxicity:  0.731
Hematotoxicity:  0.767 Drug-induced Nephrotoxicity:  0.943
Genotoxicity:  0.995 RPMI-8226 Immunitoxicity:  0.291
A549 Cytotoxicity:  0.596 Hek293 Cytotoxicity:  0.691
BCF:   1.432
?
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:   4.058
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.302
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.762
?
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
NPO17040 Peperomia duclouxii Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[16499322]
NPO17040 Peperomia duclouxii Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[17358082]
NPO17040 Peperomia duclouxii Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[17547458]
NPO17040 Peperomia duclouxii Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17040 Peperomia duclouxii Species Piperaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17040 Peperomia duclouxii Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17040 Peperomia duclouxii Species Piperaceae 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
NPT1475 Cell line WI-38 VA13 Homo sapiens IC50 = 209600.0 nM PMID[17256988]
NPT65 Cell line HepG2 Homo sapiens IC50 = 200500.0 nM PMID[25419616]
NPT2 Others Unspecified n.a. Activity = 77.0 % PMID[18172002]
NPT2 Others Unspecified n.a. Activity = 74.0 % PMID[25918997]
NPT2 Others Unspecified n.a. Activity = 86.0 % PMID[10924160]
NPT2 Others Unspecified n.a. Activity = 89.0 % PMID[10924160]
NPT2 Others Unspecified n.a. Activity = 85.0 % PMID[25918997]
NPT2 Others Unspecified n.a. Activity = 64.0 % PMID[19817445]

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 NPC216223 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
0.8571 High Similarity NPC106920
0.8571 High Similarity NPC15811
0.8475 Intermediate Similarity NPC282291
0.8475 Intermediate Similarity NPC166137
0.8103 Intermediate Similarity NPC293757
0.8103 Intermediate Similarity NPC668
0.7818 Intermediate Similarity NPC68779
0.7818 Intermediate Similarity NPC108598
0.7636 Intermediate Similarity NPC92693
0.7627 Intermediate Similarity NPC300776
0.7627 Intermediate Similarity NPC176814
0.7627 Intermediate Similarity NPC4982
0.7627 Intermediate Similarity NPC606629
0.7586 Intermediate Similarity NPC273657
0.75 Intermediate Similarity NPC40237
0.746 Intermediate Similarity NPC174512
0.7458 Intermediate Similarity NPC191158
0.7458 Intermediate Similarity NPC177644
0.7258 Intermediate Similarity NPC145569
0.7 Intermediate Similarity NPC176586
0.7 Intermediate Similarity NPC210354
0.6618 Remote Similarity NPC478703
0.6618 Remote Similarity NPC478704
0.6615 Remote Similarity NPC487679
0.6615 Remote Similarity NPC487678
0.6393 Remote Similarity NPC205915
0.6271 Remote Similarity NPC110958
0.6271 Remote Similarity NPC19890
0.625 Remote Similarity NPC72796
0.6167 Remote Similarity NPC211386
0.6119 Remote Similarity NPC76687
0.6 Remote Similarity NPC5310
0.5942 Remote Similarity NPC136757
0.5932 Remote Similarity NPC11453
0.5846 Remote Similarity NPC102908
0.5806 Remote Similarity NPC487680
0.5797 Remote Similarity NPC169973
0.5769 Remote Similarity NPC299706
0.5769 Remote Similarity NPC115466
0.5769 Remote Similarity NPC61604
0.5763 Remote Similarity NPC223807
0.5738 Remote Similarity NPC474288
0.5672 Remote Similarity NPC100675
0.5672 Remote Similarity NPC601691
0.5556 Remote Similarity NPC274356
0.5556 Remote Similarity NPC143895
0.5556 Remote Similarity NPC478705
0.5556 Remote Similarity NPC101748
0.5479 Remote Similarity NPC604694
0.5424 Remote Similarity NPC31344
0.5424 Remote Similarity NPC317769
0.5294 Remote Similarity NPC110699
0.5294 Remote Similarity NPC106055
0.5217 Remote Similarity NPC606339
0.5211 Remote Similarity NPC56184
0.5143 Remote Similarity NPC485282
0.5143 Remote Similarity NPC485283
0.5143 Remote Similarity NPC485281
0.5143 Remote Similarity NPC610284
0.5139 Remote Similarity NPC608199
0.5077 Remote Similarity NPC173308
0.5077 Remote Similarity NPC181079
0.5072 Remote Similarity NPC487677
0.5072 Remote Similarity NPC487675

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC216223 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