Natural Product: NPC67247

Natural Product IDNPC67247
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Lariciresinol Acetate
IUPAC Name [(2S,3R,4R)-2-(4-hydroxy-3-methoxyphenyl)-4-[(4-hydroxy-3-methoxyphenyl)methyl]oxolan-3-yl]methyl acetate
Synonyms Lariciresinol Acetate
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL464991
PubChem CID 10668802
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 LVYMIYJFCKIBMR-PNLZDCPESA-N
Standard InCHI InChI=1S/C22H26O7/c1-13(23)28-12-17-16(8-14-4-6-18(24)20(9-14)26-2)11-29-22(17)15-5-7-19(25)21(10-15)27-3/h4-7,9-10,16-17,22,24-25H,8,11-12H2,1-3H3/t16-,17-,22+/m0/s1
SMILES COc1cc(ccc1O)C[C@H]1CO[C@@H]([C@H]1COC(=O)C)c1ccc(c(c1)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   402.17 Volume:   406.475
?
Van der Waals volume.
Dense:   0.989 LogP:   2.1
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.055
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.975
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   18.0
TPSA:   94.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.687 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.516 Fsp3:   0.409
MCE-18:   61.903
?
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:   0.232 Fluc inhibitor:   0.278
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.017
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.288
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.209 Promiscuous compounds:   0.149

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.389 MDCK Permeability:   -4.793
Pgp-inhibitor:   0.303 Pgp-substrate:   0.481
PAMPA:   0.018
?
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%):   0.291 30% Bioavailability (F30%):   0.465
50% Bioavailability (F50%):   0.935

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.007 MRP1:   0.973
Plasma Protein Binding (PPB):   87.82% Volume Distribution (VD):   -0.178
Fu: 13.656%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.196
BSEP inhibitor:   0.757

ADMET: Metabolism

CYP1A2-inhibitor:   0.297 CYP1A2-substrate:   0.058
CYP2C19-inhibitor:   0.271 CYP2C19-substrate:   0.221
CYP2C9-inhibitor:   0.951 CYP2C9-substrate:   0.278
CYP2D6-inhibitor:   0.672 CYP2D6-substrate:   0.952
CYP3A4-inhibitor:   0.935 CYP3A4-substrate:   0.505
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.835
?
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):  6.754 Half-life (T1/2):  1.303

ADMET: Toxicity

hERG Blockers:  0.08 hERG Blockers (10um):  0.414
Human Hepatotoxicity (H-HT):  0.777 Drug-induced Liver Injury (DILI):  0.726
AMES Toxicity:  0.84 Rat Oral Acute Toxicity:  0.286
Maximum Recommended Daily Dose:  0.284 Skin Sensitization:  0.985
Carcinogencity:  0.509 Eye Corrosion:  0.017
Eye Irritation:  0.975 Respiratory Toxicity:  0.084
Drug-induced Neurotoxicity:  0.466 Ototoxicity:  0.334
Hematotoxicity:  0.327 Drug-induced Nephrotoxicity:  0.602
Genotoxicity:  0.942 RPMI-8226 Immunitoxicity:  0.122
A549 Cytotoxicity:  0.205 Hek293 Cytotoxicity:  0.306
BCF:   0.868
?
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:   3.652
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.883
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.419
?
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
NPO32616 aglaia sp. Species Meliaceae Eukaryota n.a. n.a. n.a. PMID[10775404]
NPO32616 aglaia sp. Species Meliaceae Eukaryota n.a. n.a. n.a. PMID[8496701]
NPO32616 aglaia sp. Species Meliaceae Eukaryota n.a. n.a. n.a. PMID[9868148]
NPO32616 aglaia sp. Species Meliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT776 Organism Spodoptera littoralis Spodoptera littoralis EC50 > 250.0 ug/g PMID[18591276]

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
- Spodoptera littoralis LC50 > 250.0 ug/g PMID[20713679]

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 NPC67247 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
0.8448 Intermediate Similarity NPC281780
0.75 Intermediate Similarity NPC67467
0.7258 Intermediate Similarity NPC267091
0.7069 Intermediate Similarity NPC187998
0.7069 Intermediate Similarity NPC257582
0.7069 Intermediate Similarity NPC241522
0.6786 Remote Similarity NPC487680
0.6716 Remote Similarity NPC252402
0.6716 Remote Similarity NPC102934
0.6667 Remote Similarity NPC472711
0.6552 Remote Similarity NPC610778
0.6415 Remote Similarity NPC115207
0.6415 Remote Similarity NPC158079
0.6415 Remote Similarity NPC228346
0.6415 Remote Similarity NPC40432
0.6415 Remote Similarity NPC161557
0.6406 Remote Similarity NPC471988
0.6349 Remote Similarity NPC42300
0.629 Remote Similarity NPC486558
0.629 Remote Similarity NPC282833
0.625 Remote Similarity NPC64201
0.6111 Remote Similarity NPC31344
0.6111 Remote Similarity NPC317769
0.6032 Remote Similarity NPC145144
0.5965 Remote Similarity NPC126409
0.5965 Remote Similarity NPC99572
0.5932 Remote Similarity NPC68779
0.5932 Remote Similarity NPC108598
0.5932 Remote Similarity NPC27843
0.5932 Remote Similarity NPC7171
0.5873 Remote Similarity NPC110699
0.5873 Remote Similarity NPC106055
0.5806 Remote Similarity NPC471942
0.5781 Remote Similarity NPC606339
0.5758 Remote Similarity NPC487679
0.5758 Remote Similarity NPC487678
0.5738 Remote Similarity NPC223185
0.5714 Remote Similarity NPC88640
0.5714 Remote Similarity NPC101153
0.5714 Remote Similarity NPC193666
0.5714 Remote Similarity NPC123526
0.5714 Remote Similarity NPC608725
0.5692 Remote Similarity NPC485282
0.5692 Remote Similarity NPC485283
0.5692 Remote Similarity NPC485281
0.5625 Remote Similarity NPC610652
0.5593 Remote Similarity NPC479434
0.5588 Remote Similarity NPC487682
0.5556 Remote Similarity NPC273657
0.5517 Remote Similarity NPC147379
0.5517 Remote Similarity NPC469480
0.5484 Remote Similarity NPC275950
0.5455 Remote Similarity NPC610284
0.541 Remote Similarity NPC478955
0.541 Remote Similarity NPC478700
0.5397 Remote Similarity NPC253481
0.5397 Remote Similarity NPC253722
0.5385 Remote Similarity NPC106920
0.5385 Remote Similarity NPC300776
0.5385 Remote Similarity NPC15811
0.5385 Remote Similarity NPC176814
0.5385 Remote Similarity NPC23646
0.5385 Remote Similarity NPC4982
0.5385 Remote Similarity NPC485397
0.5385 Remote Similarity NPC606629
0.5373 Remote Similarity NPC40094
0.5303 Remote Similarity NPC476345
0.5263 Remote Similarity NPC142985
0.5256 Remote Similarity NPC486545
0.5217 Remote Similarity NPC282291
0.5217 Remote Similarity NPC166137
0.5185 Remote Similarity NPC165133
0.5185 Remote Similarity NPC242885
0.5185 Remote Similarity NPC95614
0.5185 Remote Similarity NPC232316
0.5179 Remote Similarity NPC282703
0.5179 Remote Similarity NPC184733
0.5179 Remote Similarity NPC128208
0.5179 Remote Similarity NPC129570
0.5179 Remote Similarity NPC63238
0.5179 Remote Similarity NPC602603
0.5161 Remote Similarity NPC173308
0.5161 Remote Similarity NPC181079
0.5156 Remote Similarity NPC475875
0.5152 Remote Similarity NPC277804
0.5152 Remote Similarity NPC481088
0.5147 Remote Similarity NPC471505
0.5143 Remote Similarity NPC120852
0.5075 Remote Similarity NPC100675
0.5075 Remote Similarity NPC601691
0.5062 Remote Similarity NPC476356

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC67247 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