Natural Product: NPC112571

Natural Product IDNPC112571
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Ligraminol A
IUPAC Name (2S,3R,4S,5S)-2-(3,4-dimethoxyphenyl)-3,4-dimethyl-5-(3,4,5-trimethoxyphenyl)oxolane
Synonyms Ligraminol A
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1928001
PubChem CID 56599264
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid lignans
        • [CHEMONTID:0001604] Tetrahydrofuran lignans
          • [CHEMONTID:0003423] 7,7'-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 FUFHSLKNBJRCDG-RUGJYQHNSA-N
Standard InCHI InChI=1S/C23H30O6/c1-13-14(2)22(16-11-19(26-5)23(28-7)20(12-16)27-6)29-21(13)15-8-9-17(24-3)18(10-15)25-4/h8-14,21-22H,1-7H3/t13-,14+,21+,22+/m1/s1
SMILES COc1cc(ccc1OC)[C@H]1O[C@@H]([C@H]([C@H]1C)C)c1cc(OC)c(c(c1)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   402.2 Volume:   417.617
?
Van der Waals volume.
Dense:   0.963 LogP:   2.704
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.896
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.589
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The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   17.0
TPSA:   55.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.662 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.343 Fsp3:   0.478
MCE-18:   64.706
?
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:   0.236 Fluc inhibitor:   0.495
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.03
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.04
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.327 Promiscuous compounds:   0.165

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.846 MDCK Permeability:   -4.698
Pgp-inhibitor:   0.344 Pgp-substrate:   0.026
PAMPA:   0.011
?
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%):   0.023 30% Bioavailability (F30%):   0.003
50% Bioavailability (F50%):   0.697

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.649 MRP1:   0.997
Plasma Protein Binding (PPB):   89.677% Volume Distribution (VD):   0.193
Fu: 7.065%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.924
OATP1B3 inhibitor:   0.972 BCRP inhibitor:   0.25
BSEP inhibitor:   0.988

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.004
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.994
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.143
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.761
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.049
?
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):  8.582 Half-life (T1/2):  1.628

ADMET: Toxicity

hERG Blockers:  0.196 hERG Blockers (10um):  0.616
Human Hepatotoxicity (H-HT):  0.531 Drug-induced Liver Injury (DILI):  0.783
AMES Toxicity:  0.403 Rat Oral Acute Toxicity:  0.351
Maximum Recommended Daily Dose:  0.238 Skin Sensitization:  0.286
Carcinogencity:  0.724 Eye Corrosion:  0.057
Eye Irritation:  0.502 Respiratory Toxicity:  0.696
Drug-induced Neurotoxicity:  0.666 Ototoxicity:  0.61
Hematotoxicity:  0.665 Drug-induced Nephrotoxicity:  0.474
Genotoxicity:  0.056 RPMI-8226 Immunitoxicity:  0.185
A549 Cytotoxicity:  0.307 Hek293 Cytotoxicity:  0.388
BCF:   2.647
?
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:   4.123
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.527
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.935
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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
NPO5681 Acorus gramineus Species Acoraceae Eukaryota n.a. rhizome n.a. PMID[21936523]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota Rhizomes n.a. n.a. PMID[21936523]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota rhizomes n.a. n.a. PMID[22951040]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]

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
NPT81 Cell line A549 Homo sapiens IC50 = 6920.0 nM PMID[21936523]
NPT146 Cell line SK-OV-3 Homo sapiens IC50 = 9440.0 nM PMID[21936523]
NPT147 Cell line SK-MEL-2 Homo sapiens IC50 = 4530.0 nM PMID[21936523]
NPT737 Cell line HUVEC Homo sapiens IC50 = 27190.0 nM PMID[21936523]
NPT737 Cell line HUVEC Homo sapiens Ratio IC50 = 6.0 n.a. PMID[21936523]
NPT34 Cell line BV-2 Mus musculus IC50 = 21510.0 nM PMID[21936523]
NPT34 Cell line BV-2 Mus musculus Activity = 88.6 % PMID[21936523]

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 NPC112571 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 NPC50683
1.0 High Similarity NPC285725
0.8824 High Similarity NPC216929
0.8824 High Similarity NPC312713
0.8824 High Similarity NPC126935
0.8824 High Similarity NPC65933
0.8824 High Similarity NPC57268
0.8824 High Similarity NPC172676
0.8049 Intermediate Similarity NPC136750
0.8049 Intermediate Similarity NPC266848
0.7941 Intermediate Similarity NPC9891
0.7941 Intermediate Similarity NPC88297
0.7941 Intermediate Similarity NPC186845
0.7381 Intermediate Similarity NPC158331
0.7317 Intermediate Similarity NPC57119
0.7317 Intermediate Similarity NPC158471
0.7317 Intermediate Similarity NPC226862
0.6818 Remote Similarity NPC487684
0.6667 Remote Similarity NPC11258
0.6667 Remote Similarity NPC21867
0.6667 Remote Similarity NPC222127
0.6667 Remote Similarity NPC45774
0.6667 Remote Similarity NPC82862
0.6667 Remote Similarity NPC74914
0.6585 Remote Similarity NPC72046
0.6585 Remote Similarity NPC261812
0.6585 Remote Similarity NPC65183
0.6429 Remote Similarity NPC204215
0.6341 Remote Similarity NPC271208
0.6341 Remote Similarity NPC31530
0.6341 Remote Similarity NPC233224
0.6341 Remote Similarity NPC610263
0.6122 Remote Similarity NPC260842
0.6122 Remote Similarity NPC93783
0.6122 Remote Similarity NPC320380
0.6 Remote Similarity NPC175067
0.5714 Remote Similarity NPC121783
0.5714 Remote Similarity NPC34902
0.5714 Remote Similarity NPC18449
0.549 Remote Similarity NPC135777
0.549 Remote Similarity NPC7744
0.5385 Remote Similarity NPC142547
0.5385 Remote Similarity NPC228469
0.5385 Remote Similarity NPC488984
0.5385 Remote Similarity NPC488985
0.5357 Remote Similarity NPC302506
0.5357 Remote Similarity NPC241846
0.5357 Remote Similarity NPC93610
0.5306 Remote Similarity NPC189474
0.5208 Remote Similarity NPC254120
0.5179 Remote Similarity NPC179521
0.5116 Remote Similarity NPC475856
0.5111 Remote Similarity NPC282703
0.5111 Remote Similarity NPC184733
0.5111 Remote Similarity NPC128208
0.5111 Remote Similarity NPC129570
0.5111 Remote Similarity NPC63238
0.5111 Remote Similarity NPC602603
0.5106 Remote Similarity NPC606146
0.5102 Remote Similarity NPC487685
0.5085 Remote Similarity NPC470372

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC112571 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