Natural Product: NPC92693

Natural Product IDNPC92693
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-Bis[(7-Methoxy-1,3-Benzodioxol-5-Yl)Methyl]Oxolan-2-One
IUPAC Name (3S,4S)-3,4-bis[(7-methoxy-1,3-benzodioxol-5-yl)methyl]oxolan-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL491694
PubChem CID 11154204
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 SPICWNPCROOQRU-CABCVRRESA-N
Standard InCHI InChI=1S/C22H22O8/c1-24-16-5-12(7-18-20(16)29-10-27-18)3-14-9-26-22(23)15(14)4-13-6-17(25-2)21-19(8-13)28-11-30-21/h5-8,14-15H,3-4,9-11H2,1-2H3/t14-,15+/m1/s1
SMILES COc1cc(C[C@@H]2C(=O)OC[C@H]2Cc2cc(OC)c3c(c2)OCO3)cc2c1OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   414.13 Volume:   398.152
?
Van der Waals volume.
Dense:   1.04 LogP:   2.267
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.45
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.555
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   26.0
TPSA:   81.68
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   0.0 Rings:   5.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.668 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.539 Fsp3:   0.409
MCE-18:   86.387
?
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:   0.118 Fluc inhibitor:   0.364
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.054
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.357
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.288 Promiscuous compounds:   0.168

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.974 MDCK Permeability:   -4.731
Pgp-inhibitor:   0.587 Pgp-substrate:   0.008
PAMPA:   0.079
?
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%):   0.143 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.138

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.086 MRP1:   0.792
Plasma Protein Binding (PPB):   97.473% Volume Distribution (VD):   -0.193
Fu: 2.691%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.988
OATP1B3 inhibitor:   0.66 BCRP inhibitor:   0.002
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.615 CYP1A2-substrate:   0.903
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.996
CYP2C9-inhibitor:   0.006 CYP2C9-substrate:   0.935
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.97
HLM stability:   0.935
?
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):  2.044 Half-life (T1/2):  1.614

ADMET: Toxicity

hERG Blockers:  0.245 hERG Blockers (10um):  0.561
Human Hepatotoxicity (H-HT):  0.963 Drug-induced Liver Injury (DILI):  0.99
AMES Toxicity:  0.774 Rat Oral Acute Toxicity:  0.342
Maximum Recommended Daily Dose:  0.773 Skin Sensitization:  0.678
Carcinogencity:  0.915 Eye Corrosion:  0.001
Eye Irritation:  0.712 Respiratory Toxicity:  0.342
Drug-induced Neurotoxicity:  0.847 Ototoxicity:  0.743
Hematotoxicity:  0.777 Drug-induced Nephrotoxicity:  0.937
Genotoxicity:  0.991 RPMI-8226 Immunitoxicity:  0.325
A549 Cytotoxicity:  0.353 Hek293 Cytotoxicity:  0.566
BCF:   1.677
?
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:   4.248
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.871
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.186
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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 = 130300.0 nM PubChem BioAssay data set
NPT65 Cell line HepG2 Homo sapiens IC50 = 207900.0 nM PMID[17625894]
NPT2 Others Unspecified n.a. Activity = 93.0 % PMID[18955526]
NPT2 Others Unspecified n.a. Activity = 104.0 % PMID[11720532]
NPT2 Others Unspecified n.a. Activity = 91.0 % PMID[20450206]
NPT2 Others Unspecified n.a. Activity = 86.0 % PMID[20450206]
NPT2 Others Unspecified n.a. Activity = 116.0 % PMID[9090869]
NPT2 Others Unspecified n.a. Activity = 81.0 % PMID[20429511]

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 NPC92693 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
0.9767 High Similarity NPC40237
0.875 High Similarity NPC191158
0.875 High Similarity NPC177644
0.84 Intermediate Similarity NPC293757
0.84 Intermediate Similarity NPC668
0.8163 Intermediate Similarity NPC176586
0.8163 Intermediate Similarity NPC210354
0.814 Intermediate Similarity NPC72796
0.7636 Intermediate Similarity NPC174512
0.7636 Intermediate Similarity NPC216223
0.7609 Intermediate Similarity NPC11453
0.74 Intermediate Similarity NPC205915
0.7292 Intermediate Similarity NPC110958
0.7292 Intermediate Similarity NPC19890
0.7143 Intermediate Similarity NPC211386
0.6786 Remote Similarity NPC145569
0.6667 Remote Similarity NPC223807
0.6379 Remote Similarity NPC76687
0.6346 Remote Similarity NPC143895
0.6275 Remote Similarity NPC474288
0.6271 Remote Similarity NPC282291
0.6271 Remote Similarity NPC166137
0.625 Remote Similarity NPC106920
0.625 Remote Similarity NPC15811
0.6167 Remote Similarity NPC136757
0.5833 Remote Similarity NPC482889
0.5763 Remote Similarity NPC262455
0.5763 Remote Similarity NPC177476
0.5741 Remote Similarity NPC283949
0.5667 Remote Similarity NPC480477
0.566 Remote Similarity NPC192255
0.5574 Remote Similarity NPC56184
0.551 Remote Similarity NPC150534
0.549 Remote Similarity NPC476748
0.5472 Remote Similarity NPC218841
0.5455 Remote Similarity NPC68779
0.5455 Remote Similarity NPC108598
0.5424 Remote Similarity NPC5310
0.5424 Remote Similarity NPC300776
0.5424 Remote Similarity NPC176814
0.5424 Remote Similarity NPC4982
0.5424 Remote Similarity NPC606629
0.541 Remote Similarity NPC149505
0.537 Remote Similarity NPC151423
0.5345 Remote Similarity NPC46591
0.5345 Remote Similarity NPC226547
0.5345 Remote Similarity NPC273657
0.5333 Remote Similarity NPC80230
0.5333 Remote Similarity NPC104024
0.5333 Remote Similarity NPC101755
0.5333 Remote Similarity NPC304687
0.5333 Remote Similarity NPC65574
0.5263 Remote Similarity NPC164082
0.5172 Remote Similarity NPC477698
0.5091 Remote Similarity NPC143092
0.5091 Remote Similarity NPC193779

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC92693 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