Natural Product: NPC206882

Natural Product IDNPC206882
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (+)-Lariciresinol Dimethyl Ether
IUPAC Name [(2S,3R,4R)-2-(3,4-dimethoxyphenyl)-4-[(3,4-dimethoxyphenyl)methyl]oxolan-3-yl]methanol
Synonyms (+)-Lariciresinol Dimethyl Ether
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1760590
PubChem CID 181325
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid lignans
        • [CHEMONTID:0001604] Tetrahydrofuran lignans
          • [CHEMONTID:0003422] 7,9'-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 AYWPHVUFQNWITL-PNLZDCPESA-N
Standard InCHI InChI=1S/C22H28O6/c1-24-18-7-5-14(10-20(18)26-3)9-16-13-28-22(17(16)12-23)15-6-8-19(25-2)21(11-15)27-4/h5-8,10-11,16-17,22-23H,9,12-13H2,1-4H3/t16-,17-,22+/m0/s1
SMILES OC[C@H]1[C@H](CO[C@@H]1c1ccc(c(c1)OC)OC)Cc1ccc(c(c1)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   388.19 Volume:   400.321
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Van der Waals volume.
Dense:   0.97 LogP:   1.98
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.223
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.241
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The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   17.0
TPSA:   66.38
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.749 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.247 Fsp3:   0.455
MCE-18:   58.5
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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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.254 Fluc inhibitor:   0.591
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.019
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.103
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.136 Promiscuous compounds:   0.284

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.902 MDCK Permeability:   -4.872
Pgp-inhibitor:   0.735 Pgp-substrate:   0.498
PAMPA:   0.039
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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):   0.014
20% Bioavailability (F20%):   0.125 30% Bioavailability (F30%):   0.09
50% Bioavailability (F50%):   0.647

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.029 MRP1:   0.711
Plasma Protein Binding (PPB):   83.427% Volume Distribution (VD):   0.248
Fu: 13.524%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.976
OATP1B3 inhibitor:   0.988 BCRP inhibitor:   0.703
BSEP inhibitor:   0.989

ADMET: Metabolism

CYP1A2-inhibitor:   0.983 CYP1A2-substrate:   0.012
CYP2C19-inhibitor:   0.997 CYP2C19-substrate:   0.033
CYP2C9-inhibitor:   0.971 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.994
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.636
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.874
HLM stability:   0.189
?
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):  9.361 Half-life (T1/2):  1.696

ADMET: Toxicity

hERG Blockers:  0.171 hERG Blockers (10um):  0.362
Human Hepatotoxicity (H-HT):  0.871 Drug-induced Liver Injury (DILI):  0.842
AMES Toxicity:  0.734 Rat Oral Acute Toxicity:  0.207
Maximum Recommended Daily Dose:  0.183 Skin Sensitization:  0.934
Carcinogencity:  0.63 Eye Corrosion:  0.024
Eye Irritation:  0.967 Respiratory Toxicity:  0.137
Drug-induced Neurotoxicity:  0.701 Ototoxicity:  0.581
Hematotoxicity:  0.543 Drug-induced Nephrotoxicity:  0.652
Genotoxicity:  0.595 RPMI-8226 Immunitoxicity:  0.113
A549 Cytotoxicity:  0.116 Hek293 Cytotoxicity:  0.245
BCF:   1.294
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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:   3.607
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.111
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.222
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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
NPO4001 Berberis koreana Species Berberidaceae Eukaryota n.a. n.a. n.a. PMID[19813743]
NPO4001 Berberis koreana Species Berberidaceae Eukaryota trunk Jeju island, Korea 2005-Dec PMID[21420296]
NPO4001 Berberis koreana Species Berberidaceae Eukaryota n.a. n.a. n.a. PMID[21420296]
NPO4001 Berberis koreana Species Berberidaceae 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
NPT34 Cell line BV-2 Mus musculus IC50 = 44420.0 nM PMID[18293924]
NPT81 Cell line A549 Homo sapiens IC50 = 20130.0 nM PMID[22037378]
NPT147 Cell line SK-MEL-2 Homo sapiens IC50 = 25120.0 nM PMID[19001116]
NPT574 Cell line XF498 Homo sapiens IC50 = 15400.0 nM PubChem BioAssay data set
NPT146 Cell line SK-OV-3 Homo sapiens IC50 = 21500.0 nM DOI[10.1016/j.cropro.2012.04.001]

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 NPC206882 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
0.7885 Intermediate Similarity NPC47181
0.7818 Intermediate Similarity NPC64201
0.6875 Remote Similarity NPC471063
0.6429 Remote Similarity NPC46591
0.6316 Remote Similarity NPC187998
0.6316 Remote Similarity NPC257582
0.6316 Remote Similarity NPC241522
0.617 Remote Similarity NPC81067
0.617 Remote Similarity NPC602945
0.6167 Remote Similarity NPC40094
0.6071 Remote Similarity NPC30890
0.5902 Remote Similarity NPC42300
0.5833 Remote Similarity NPC486558
0.5833 Remote Similarity NPC282833
0.5753 Remote Similarity NPC185307
0.5753 Remote Similarity NPC470950
0.5714 Remote Similarity NPC121783
0.5714 Remote Similarity NPC34902
0.5714 Remote Similarity NPC18449
0.5694 Remote Similarity NPC39657
0.5676 Remote Similarity NPC476356
0.5517 Remote Similarity NPC481089
0.5455 Remote Similarity NPC482890
0.5397 Remote Similarity NPC600032
0.5333 Remote Similarity NPC62354
0.5283 Remote Similarity NPC222127
0.5283 Remote Similarity NPC82862
0.5091 Remote Similarity NPC223807

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC206882 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