Natural Product: NPC12728

Natural Product IDNPC12728
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (1S,2R,5S,6R)-2-(5-Methoxy-3,4-Methylenedioxyphenyl)-6-(3,4-Dihydroxy-5-Methoxyphenyl)-3,7-Dioxabicyclo[3.3.0]Octane
IUPAC Name 5-[(3R,3aS,6R,6aS)-6-(7-methoxy-1,3-benzodioxol-5-yl)-1,3,3a,4,6,6a-hexahydrofuro[3,4-c]furan-3-yl]-3-methoxybenzene-1,2-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL376820
PubChem CID 16215160
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid 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 VVGTYCADBJEFMD-VLSDQLEDSA-N
Standard InCHI InChI=1S/C21H22O8/c1-24-15-4-10(3-14(22)18(15)23)19-12-7-27-20(13(12)8-26-19)11-5-16(25-2)21-17(6-11)28-9-29-21/h3-6,12-13,19-20,22-23H,7-9H2,1-2H3/t12-,13-,19+,20+/m1/s1
SMILES COc1cc(cc(c1O)O)[C@@H]1OC[C@@H]2[C@H]1CO[C@H]2c1cc(OC)c2c(c1)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   402.13 Volume:   383.493
?
Van der Waals volume.
Dense:   1.049 LogP:   1.385
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.867
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.389
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   25.0
TPSA:   95.84
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   2.0 Rings:   5.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.754 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.005 Fsp3:   0.429
MCE-18:   93.6
?
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:   0.456 Fluc inhibitor:   0.377
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.036
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.18
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.231 Promiscuous compounds:   0.548

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.285 MDCK Permeability:   -4.885
Pgp-inhibitor:   0.054 Pgp-substrate:   0.023
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):   0.001
20% Bioavailability (F20%):   0.156 30% Bioavailability (F30%):   0.02
50% Bioavailability (F50%):   0.774

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.645 MRP1:   0.95
Plasma Protein Binding (PPB):   87.444% Volume Distribution (VD):   -0.397
Fu: 11.549%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.521
BSEP inhibitor:   0.823

ADMET: Metabolism

CYP1A2-inhibitor:   0.97 CYP1A2-substrate:   0.406
CYP2C19-inhibitor:   0.993 CYP2C19-substrate:   0.301
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.604
CYP2D6-inhibitor:   0.007 CYP2D6-substrate:   0.829
CYP3A4-inhibitor:   0.596 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.501
HLM stability:   0.262
?
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):  6.881 Half-life (T1/2):  2.193

ADMET: Toxicity

hERG Blockers:  0.111 hERG Blockers (10um):  0.451
Human Hepatotoxicity (H-HT):  0.817 Drug-induced Liver Injury (DILI):  0.953
AMES Toxicity:  0.75 Rat Oral Acute Toxicity:  0.277
Maximum Recommended Daily Dose:  0.539 Skin Sensitization:  0.942
Carcinogencity:  0.711 Eye Corrosion:  0.005
Eye Irritation:  0.925 Respiratory Toxicity:  0.314
Drug-induced Neurotoxicity:  0.316 Ototoxicity:  0.448
Hematotoxicity:  0.362 Drug-induced Nephrotoxicity:  0.438
Genotoxicity:  0.914 RPMI-8226 Immunitoxicity:  0.126
A549 Cytotoxicity:  0.551 Hek293 Cytotoxicity:  0.338
BCF:   1.51
?
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:   3.852
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.665
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.759
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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
NPT1374 Cell line WI-38 Homo sapiens IC50 = 49.8 ug.mL-1 PMID[26132528]
NPT1475 Cell line WI-38 VA13 Homo sapiens IC50 = 5.3 ug.mL-1 PMID[12444692]
NPT65 Cell line HepG2 Homo sapiens IC50 = 13.2 ug.mL-1 PMID[10924160]
NPT2 Others Unspecified n.a. Activity = 101.0 % PMID[26211462]
NPT2 Others Unspecified n.a. Activity = 105.0 % PMID[17618015]
NPT2 Others Unspecified n.a. Activity = 169.0 % PMID[17618015]
NPT2 Others Unspecified n.a. Activity = 103.0 % PMID[17618015]
NPT2 Others Unspecified n.a. Activity = 92.0 % PMID[17618015]
NPT2 Others Unspecified n.a. Activity = 117.0 % PMID[17618015]

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 NPC12728 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
0.7843 Intermediate Similarity NPC185071
0.7143 Intermediate Similarity NPC148893
0.7143 Intermediate Similarity NPC25333
0.7143 Intermediate Similarity NPC49235
0.6346 Remote Similarity NPC165155
0.6346 Remote Similarity NPC24490
0.6207 Remote Similarity NPC298317
0.6207 Remote Similarity NPC255566
0.5902 Remote Similarity NPC477702
0.5893 Remote Similarity NPC189474
0.5738 Remote Similarity NPC88640
0.5738 Remote Similarity NPC101153
0.5738 Remote Similarity NPC193666
0.5738 Remote Similarity NPC123526
0.5738 Remote Similarity NPC608725
0.5714 Remote Similarity NPC281864
0.5714 Remote Similarity NPC328682
0.5714 Remote Similarity NPC54321
0.5686 Remote Similarity NPC141765
0.5686 Remote Similarity NPC34103
0.5333 Remote Similarity NPC177868
0.5263 Remote Similarity NPC227160
0.5263 Remote Similarity NPC82111
0.5185 Remote Similarity NPC473092
0.5185 Remote Similarity NPC473093
0.5185 Remote Similarity NPC8050
0.5147 Remote Similarity NPC212890
0.5143 Remote Similarity NPC486102
0.5091 Remote Similarity NPC171928
0.5091 Remote Similarity NPC158526
0.5091 Remote Similarity NPC129687
0.5091 Remote Similarity NPC33611
0.5091 Remote Similarity NPC16830
0.5091 Remote Similarity NPC100223
0.5079 Remote Similarity NPC46591

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC12728 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