Natural Product: NPC477701

Natural Product IDNPC477701
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Acetic acid [(2S)-2alpha,5alpha-bis(4-methoxy-1,3-benzodioxole-6-yl)-3beta-(hydroxymethyl)tetrahydrofuran]-4alpha-ylmethyl ester
IUPAC Name [(2R,3R,4R,5S)-4-(hydroxymethyl)-2,5-bis(7-methoxy-1,3-benzodioxol-5-yl)oxolan-3-yl]methyl acetate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11590987
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid lignans
        • [CHEMONTID:0001604] Tetrahydrofuran lignans
          • [CHEMONTID:0003423] 7,7'-epoxylignans

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 YPQDTAINIDFHAR-FRMGNDQPSA-N
Standard InCHI InChI=1S/C24H26O10/c1-12(26)29-9-16-15(8-25)21(13-4-17(27-2)23-19(6-13)30-10-32-23)34-22(16)14-5-18(28-3)24-20(7-14)31-11-33-24/h4-7,15-16,21-22,25H,8-11H2,1-3H3/t15-,16-,21+,22-/m0/s1
SMILES CC(=O)OC[C@H]1[C@@H]([C@H](O[C@H]1C2=CC3=C(C(=C2)OC)OCO3)C4=CC5=C(C(=C4)OC)OCO5)CO

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   474.15 Volume:   450.325
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Van der Waals volume.
Dense:   1.053 LogP:   1.98
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.414
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.618
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The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   26.0
TPSA:   111.14
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Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.601 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.072 Fsp3:   0.458
MCE-18:   93.6
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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:   0 PAINS Alert:   0
Colloidal aggregators:   0.599 Fluc inhibitor:   0.272
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.041
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.306
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.091 Promiscuous compounds:   0.413

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.235 MDCK Permeability:   -4.873
Pgp-inhibitor:   0.301 Pgp-substrate:   0.001
PAMPA:   0.069
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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%):   0.0 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.161

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.598 MRP1:   0.947
Plasma Protein Binding (PPB):   88.004% Volume Distribution (VD):   0.135
Fu: 12.562%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.981
OATP1B3 inhibitor:   0.855 BCRP inhibitor:   0.002
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.976 CYP1A2-substrate:   0.413
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.763
CYP2C9-inhibitor:   0.011 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.987
CYP3A4-inhibitor:   0.006 CYP3A4-substrate:   0.961
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.295
HLM stability:   0.57
?
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):  3.021 Half-life (T1/2):  1.586

ADMET: Toxicity

hERG Blockers:  0.081 hERG Blockers (10um):  0.26
Human Hepatotoxicity (H-HT):  0.672 Drug-induced Liver Injury (DILI):  0.898
AMES Toxicity:  0.781 Rat Oral Acute Toxicity:  0.239
Maximum Recommended Daily Dose:  0.435 Skin Sensitization:  0.777
Carcinogencity:  0.892 Eye Corrosion:  0.001
Eye Irritation:  0.455 Respiratory Toxicity:  0.112
Drug-induced Neurotoxicity:  0.495 Ototoxicity:  0.634
Hematotoxicity:  0.739 Drug-induced Nephrotoxicity:  0.62
Genotoxicity:  0.906 RPMI-8226 Immunitoxicity:  0.134
A549 Cytotoxicity:  0.129 Hek293 Cytotoxicity:  0.338
BCF:   0.933
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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:   3.57
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.538
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.479
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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
NPO27718 Peperomia dindygulensis Species Piperaceae Eukaryota whole plant Yunnan Province, China 2002-FEB PMID[16309318]
NPO27718 Peperomia dindygulensis Species Piperaceae Eukaryota whole plant Yunnan Province, China 2002-FEB PMID[16724842]
NPO27718 Peperomia dindygulensis 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
NPT668 Individual protein P-glycoprotein 1 Homo sapiens Inhibition = 76 % PMID[16309318]
NPT668 Individual protein P-glycoprotein 1 Homo sapiens Inhibition = 85 % PMID[16309318]
NPT668 Individual protein P-glycoprotein 1 Homo sapiens Inhibition = 94 % PMID[16309318]
NPT668 Individual protein P-glycoprotein 1 Homo sapiens Inhibition = 86 % PMID[16309318]
NPT668 Individual protein P-glycoprotein 1 Homo sapiens Inhibition = 89 % PMID[16309318]
NPT668 Individual protein P-glycoprotein 1 Homo sapiens Inhibition = 72 % PMID[16309318]

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





 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 NPC477701 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 NPC166884
1.0 High Similarity NPC141569
0.9796 High Similarity NPC287124
0.8727 High Similarity NPC212890
0.7321 Intermediate Similarity NPC477702
0.5882 Remote Similarity NPC31530
0.5769 Remote Similarity NPC72046
0.5769 Remote Similarity NPC261812
0.5769 Remote Similarity NPC65183
0.5574 Remote Similarity NPC46591
0.5556 Remote Similarity NPC148893
0.5556 Remote Similarity NPC25333
0.5556 Remote Similarity NPC49235
0.5536 Remote Similarity NPC11453
0.5439 Remote Similarity NPC487685
0.5439 Remote Similarity NPC136750
0.5439 Remote Similarity NPC266848
0.5373 Remote Similarity NPC487682
0.5167 Remote Similarity NPC185071
0.5085 Remote Similarity NPC189474
0.5082 Remote Similarity NPC177868

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC477701 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