Natural Product: NPC145569

Natural Product IDNPC145569
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (3S,4S)-4-(1,3-Benzodioxol-5-Ylmethyl)-3-[(4-Hydroxy-3,5-Dimethoxyphenyl)Methyl]Oxolan-2-One
IUPAC Name (3S,4S)-4-(1,3-benzodioxol-5-ylmethyl)-3-[(4-hydroxy-3,5-dimethoxyphenyl)methyl]oxolan-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL522851
PubChem CID 11176633
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 DZBHCHXEAGTVGF-CABCVRRESA-N
Standard InCHI InChI=1S/C21H22O7/c1-24-18-8-13(9-19(25-2)20(18)22)6-15-14(10-26-21(15)23)5-12-3-4-16-17(7-12)28-11-27-16/h3-4,7-9,14-15,22H,5-6,10-11H2,1-2H3/t14-,15+/m1/s1
SMILES COc1cc(C[C@@H]2C(=O)OC[C@H]2Cc2ccc3c(c2)OCO3)cc(c1O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   386.14 Volume:   380.623
?
Van der Waals volume.
Dense:   1.014 LogP:   2.089
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.294
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.903
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   22.0
TPSA:   83.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.764 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.277 Fsp3:   0.381
MCE-18:   72.069
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.228 Fluc inhibitor:   0.391
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.023
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.343
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.244 Promiscuous compounds:   0.2

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.062 MDCK Permeability:   -4.78
Pgp-inhibitor:   0.758 Pgp-substrate:   0.038
PAMPA:   0.006
?
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%):   0.127 30% Bioavailability (F30%):   0.004
50% Bioavailability (F50%):   0.591

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.094 MRP1:   0.934
Plasma Protein Binding (PPB):   98.259% Volume Distribution (VD):   -0.41
Fu: 1.507%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.926 BCRP inhibitor:   0.015
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.147 CYP1A2-substrate:   0.997
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.679 CYP2C9-substrate:   0.994
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.999
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.907
?
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):  4.426 Half-life (T1/2):  1.562

ADMET: Toxicity

hERG Blockers:  0.277 hERG Blockers (10um):  0.596
Human Hepatotoxicity (H-HT):  0.93 Drug-induced Liver Injury (DILI):  0.986
AMES Toxicity:  0.665 Rat Oral Acute Toxicity:  0.599
Maximum Recommended Daily Dose:  0.658 Skin Sensitization:  0.942
Carcinogencity:  0.821 Eye Corrosion:  0.001
Eye Irritation:  0.701 Respiratory Toxicity:  0.544
Drug-induced Neurotoxicity:  0.889 Ototoxicity:  0.711
Hematotoxicity:  0.764 Drug-induced Nephrotoxicity:  0.935
Genotoxicity:  0.994 RPMI-8226 Immunitoxicity:  0.275
A549 Cytotoxicity:  0.472 Hek293 Cytotoxicity:  0.627
BCF:   1.352
?
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:   4.064
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.405
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.859
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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 = 183300.0 nM PMID[19296616]
NPT65 Cell line HepG2 Homo sapiens IC50 > 260000.0 nM PMID[25466192]
NPT2 Others Unspecified n.a. Activity = 93.0 % PMID[23363020]
NPT2 Others Unspecified n.a. Activity = 90.0 % PMID[23993676]
NPT2 Others Unspecified n.a. Activity = 94.0 % PMID[11170670]
NPT2 Others Unspecified n.a. Activity = 97.0 % PMID[10560746]
NPT2 Others Unspecified n.a. Activity = 127.0 % PMID[10560746]
NPT2 Others Unspecified n.a. Activity = 96.0 % PMID[10560746]

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 NPC145569 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
0.8276 Intermediate Similarity NPC282291
0.8276 Intermediate Similarity NPC166137
0.8214 Intermediate Similarity NPC293757
0.8214 Intermediate Similarity NPC668
0.8 Intermediate Similarity NPC176586
0.8 Intermediate Similarity NPC210354
0.7963 Intermediate Similarity NPC205915
0.7885 Intermediate Similarity NPC110958
0.7885 Intermediate Similarity NPC19890
0.7857 Intermediate Similarity NPC191158
0.7857 Intermediate Similarity NPC177644
0.7258 Intermediate Similarity NPC216223
0.7069 Intermediate Similarity NPC273657
0.6833 Remote Similarity NPC300776
0.6833 Remote Similarity NPC176814
0.6833 Remote Similarity NPC4982
0.6833 Remote Similarity NPC606629
0.6786 Remote Similarity NPC92693
0.6769 Remote Similarity NPC478705
0.6719 Remote Similarity NPC174512
0.6667 Remote Similarity NPC223807
0.6667 Remote Similarity NPC40237
0.6557 Remote Similarity NPC106920
0.6557 Remote Similarity NPC15811
0.6491 Remote Similarity NPC211386
0.6406 Remote Similarity NPC487679
0.6406 Remote Similarity NPC487678
0.6379 Remote Similarity NPC68779
0.6379 Remote Similarity NPC108598
0.6379 Remote Similarity NPC143895
0.629 Remote Similarity NPC5310
0.6182 Remote Similarity NPC476748
0.6154 Remote Similarity NPC76687
0.6 Remote Similarity NPC72796
0.597 Remote Similarity NPC136757
0.5942 Remote Similarity NPC478703
0.5942 Remote Similarity NPC478704
0.5909 Remote Similarity NPC56184
0.5781 Remote Similarity NPC3982
0.5763 Remote Similarity NPC192255
0.5763 Remote Similarity NPC474288
0.5588 Remote Similarity NPC169973
0.5536 Remote Similarity NPC600801
0.5424 Remote Similarity NPC11453
0.5385 Remote Similarity NPC185908
0.5385 Remote Similarity NPC482891
0.5362 Remote Similarity NPC30009
0.5362 Remote Similarity NPC103197
0.5323 Remote Similarity NPC158737
0.5323 Remote Similarity NPC274356
0.5323 Remote Similarity NPC101748
0.519 Remote Similarity NPC299706
0.519 Remote Similarity NPC115466
0.519 Remote Similarity NPC61604
0.5161 Remote Similarity NPC171550
0.5161 Remote Similarity NPC134764

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC145569 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