Natural Product: NPC668

Natural Product IDNPC668
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-3,5-Dimethoxyphenyl)Methyl]-4-[(7-Methoxy-1,3-Benzodioxol-5-Yl)Methyl]Oxolan-2-One
IUPAC Name (3S,4S)-3-[(4-hydroxy-3,5-dimethoxyphenyl)methyl]-4-[(7-methoxy-1,3-benzodioxol-5-yl)methyl]oxolan-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL524185
PubChem CID 11327496
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 PXGBYNPVEFKJGA-CABCVRRESA-N
Standard InCHI InChI=1S/C22H24O8/c1-25-16-6-13(7-17(26-2)20(16)23)5-15-14(10-28-22(15)24)4-12-8-18(27-3)21-19(9-12)29-11-30-21/h6-9,14-15,23H,4-5,10-11H2,1-3H3/t14-,15+/m1/s1
SMILES COc1cc(C[C@@H]2C(=O)OC[C@H]2Cc2cc(OC)c3c(c2)OCO3)cc(c1O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   416.15 Volume:   406.709
?
Van der Waals volume.
Dense:   1.023 LogP:   1.916
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.246
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.676
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The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   22.0
TPSA:   92.68
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.689 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.43 Fsp3:   0.409
MCE-18:   74.935
?
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:   0
Colloidal aggregators:   0.169 Fluc inhibitor:   0.147
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.035
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.377
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.248 Promiscuous compounds:   0.295

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.111 MDCK Permeability:   -4.771
Pgp-inhibitor:   0.806 Pgp-substrate:   0.056
PAMPA:   0.002
?
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%):   0.14 30% Bioavailability (F30%):   0.007
50% Bioavailability (F50%):   0.506

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.022 MRP1:   0.948
Plasma Protein Binding (PPB):   97.643% Volume Distribution (VD):   -0.503
Fu: 2.187%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.955 BCRP inhibitor:   0.034
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.232 CYP1A2-substrate:   0.991
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.772 CYP2C9-substrate:   0.855
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.975
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.912
?
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):  4.42 Half-life (T1/2):  1.677

ADMET: Toxicity

hERG Blockers:  0.292 hERG Blockers (10um):  0.595
Human Hepatotoxicity (H-HT):  0.93 Drug-induced Liver Injury (DILI):  0.984
AMES Toxicity:  0.557 Rat Oral Acute Toxicity:  0.65
Maximum Recommended Daily Dose:  0.733 Skin Sensitization:  0.937
Carcinogencity:  0.806 Eye Corrosion:  0.0
Eye Irritation:  0.624 Respiratory Toxicity:  0.678
Drug-induced Neurotoxicity:  0.901 Ototoxicity:  0.766
Hematotoxicity:  0.804 Drug-induced Nephrotoxicity:  0.944
Genotoxicity:  0.99 RPMI-8226 Immunitoxicity:  0.326
A549 Cytotoxicity:  0.527 Hek293 Cytotoxicity:  0.622
BCF:   1.421
?
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:   4.091
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.342
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.822
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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 = 130400.0 nM PMID[17970595]
NPT65 Cell line HepG2 Homo sapiens IC50 = 204500.0 nM PMID[25419616]
NPT2 Others Unspecified n.a. Activity = 86.0 % PMID[10924166]
NPT2 Others Unspecified n.a. Activity = 83.0 % PMID[10924160]
NPT2 Others Unspecified n.a. Activity = 91.0 % PMID[10924166]
NPT2 Others Unspecified n.a. Activity = 94.0 % PMID[25918997]
NPT2 Others Unspecified n.a. Activity = 129.0 % PMID[25918997]
NPT2 Others Unspecified n.a. Activity = 97.0 % PMID[1431942]

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 NPC668 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 NPC293757
0.84 Intermediate Similarity NPC92693
0.8235 Intermediate Similarity NPC40237
0.8214 Intermediate Similarity NPC145569
0.8103 Intermediate Similarity NPC174512
0.8103 Intermediate Similarity NPC216223
0.75 Intermediate Similarity NPC191158
0.75 Intermediate Similarity NPC177644
0.7458 Intermediate Similarity NPC76687
0.7213 Intermediate Similarity NPC136757
0.7018 Intermediate Similarity NPC176586
0.7018 Intermediate Similarity NPC210354
0.6863 Remote Similarity NPC72796
0.678 Remote Similarity NPC106920
0.678 Remote Similarity NPC15811
0.6774 Remote Similarity NPC282291
0.6774 Remote Similarity NPC166137
0.6724 Remote Similarity NPC273657
0.6481 Remote Similarity NPC11453
0.6379 Remote Similarity NPC205915
0.625 Remote Similarity NPC110958
0.625 Remote Similarity NPC19890
0.614 Remote Similarity NPC211386
0.6034 Remote Similarity NPC68779
0.6034 Remote Similarity NPC108598
0.597 Remote Similarity NPC478705
0.5968 Remote Similarity NPC300776
0.5968 Remote Similarity NPC176814
0.5968 Remote Similarity NPC4982
0.5968 Remote Similarity NPC606629
0.5909 Remote Similarity NPC32079
0.5806 Remote Similarity NPC477695
0.5714 Remote Similarity NPC223807
0.5606 Remote Similarity NPC477699
0.55 Remote Similarity NPC143895
0.5469 Remote Similarity NPC5310
0.5469 Remote Similarity NPC477700
0.5424 Remote Similarity NPC474288
0.5294 Remote Similarity NPC30009
0.5294 Remote Similarity NPC103197
0.5246 Remote Similarity NPC283949
0.5231 Remote Similarity NPC477702
0.5211 Remote Similarity NPC24425
0.5211 Remote Similarity NPC478703
0.5211 Remote Similarity NPC478704
0.5147 Remote Similarity NPC487679
0.5147 Remote Similarity NPC56184
0.5147 Remote Similarity NPC487678
0.5147 Remote Similarity NPC482889
0.5075 Remote Similarity NPC262455
0.5075 Remote Similarity NPC177476

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC668 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