Natural Product: NPC174512

Natural Product IDNPC174512
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2S,3S)-2-(3,4-Dihydroxy-5-Methoxybenzyl)-3-(5-Methoxy-3,4-Methylenedioxybenzyl)Butyrolactone
IUPAC Name (3S,4S)-3-[(3,4-dihydroxy-5-methoxyphenyl)methyl]-4-[(7-methoxy-1,3-benzodioxol-5-yl)methyl]oxolan-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL523313
PubChem CID 11625522
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 LGXHPTUKHKWYCU-KGLIPLIRSA-N
Standard InCHI InChI=1S/C21H22O8/c1-25-16-6-12(5-15(22)19(16)23)4-14-13(9-27-21(14)24)3-11-7-17(26-2)20-18(8-11)28-10-29-20/h5-8,13-14,22-23H,3-4,9-10H2,1-2H3/t13-,14+/m1/s1
SMILES COc1cc(C[C@H]2[C@H](Cc3cc(c4c(c3)OCO4)OC)COC2=O)cc(c1O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   402.13 Volume:   389.413
?
Van der Waals volume.
Dense:   1.033 LogP:   1.761
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.997
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.874
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   22.0
TPSA:   103.68
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.561 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.511 Fsp3:   0.381
MCE-18:   75.345
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.378 Fluc inhibitor:   0.058
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.032
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.394
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.248 Promiscuous compounds:   0.283

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.077 MDCK Permeability:   -4.769
Pgp-inhibitor:   0.3 Pgp-substrate:   0.015
PAMPA:   0.019
?
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):   0.003
20% Bioavailability (F20%):   0.771 30% Bioavailability (F30%):   0.222
50% Bioavailability (F50%):   0.892

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.863
Plasma Protein Binding (PPB):   96.786% Volume Distribution (VD):   -0.541
Fu: 3.337%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.977 BCRP inhibitor:   0.046
BSEP inhibitor:   0.996

ADMET: Metabolism

CYP1A2-inhibitor:   0.006 CYP1A2-substrate:   0.743
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.998
CYP2C9-inhibitor:   0.354 CYP2C9-substrate:   0.812
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.989
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.949
?
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):  6.469 Half-life (T1/2):  1.68

ADMET: Toxicity

hERG Blockers:  0.282 hERG Blockers (10um):  0.637
Human Hepatotoxicity (H-HT):  0.948 Drug-induced Liver Injury (DILI):  0.989
AMES Toxicity:  0.651 Rat Oral Acute Toxicity:  0.591
Maximum Recommended Daily Dose:  0.763 Skin Sensitization:  0.99
Carcinogencity:  0.757 Eye Corrosion:  0.001
Eye Irritation:  0.816 Respiratory Toxicity:  0.557
Drug-induced Neurotoxicity:  0.806 Ototoxicity:  0.864
Hematotoxicity:  0.713 Drug-induced Nephrotoxicity:  0.918
Genotoxicity:  0.996 RPMI-8226 Immunitoxicity:  0.186
A549 Cytotoxicity:  0.771 Hek293 Cytotoxicity:  0.56
BCF:   1.36
?
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:   4.02
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.482
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.91
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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
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 = 181400.0 nM PMID[20684562]
NPT65 Cell line HepG2 Homo sapiens IC50 = 162400.0 nM DailyMed
NPT2 Others Unspecified n.a. Activity = 98.0 % PMID[18778877]
NPT2 Others Unspecified n.a. Activity = 110.0 % PMID[10978195]
NPT2 Others Unspecified n.a. Activity = 91.0 % PMID[17618711]
NPT2 Others Unspecified n.a. Activity = 86.0 % PMID[18630962]
NPT2 Others Unspecified n.a. Activity = 120.0 % DOI[10.6019/CHEMBL1201861]
NPT2 Others Unspecified n.a. Activity = 84.0 % PMID[18630962]

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 NPC174512 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
0.8103 Intermediate Similarity NPC293757
0.8103 Intermediate Similarity NPC668
0.7636 Intermediate Similarity NPC92693
0.75 Intermediate Similarity NPC40237
0.746 Intermediate Similarity NPC216223
0.6885 Remote Similarity NPC191158
0.6885 Remote Similarity NPC177644
0.6719 Remote Similarity NPC145569
0.6452 Remote Similarity NPC176586
0.6452 Remote Similarity NPC210354
0.6269 Remote Similarity NPC282291
0.6269 Remote Similarity NPC166137
0.625 Remote Similarity NPC106920
0.625 Remote Similarity NPC15811
0.625 Remote Similarity NPC72796
0.6119 Remote Similarity NPC76687
0.5942 Remote Similarity NPC136757
0.5932 Remote Similarity NPC11453
0.5873 Remote Similarity NPC205915
0.5758 Remote Similarity NPC5310
0.5738 Remote Similarity NPC110958
0.5738 Remote Similarity NPC19890
0.5645 Remote Similarity NPC211386
0.5556 Remote Similarity NPC68779
0.5556 Remote Similarity NPC108598
0.5522 Remote Similarity NPC300776
0.5522 Remote Similarity NPC176814
0.5522 Remote Similarity NPC4982
0.5522 Remote Similarity NPC606629
0.5455 Remote Similarity NPC273657
0.5246 Remote Similarity NPC223807
0.5135 Remote Similarity NPC478705
0.5077 Remote Similarity NPC143895

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC174512 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