Natural Product: NPC222004

Natural Product IDNPC222004
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (1S,2S)-2-[2-Methoxy-4-[(E)-Prop-1-Enyl]Phenoxy]-1-(3,4,5-Trimethoxyphenyl)Propan-1-Ol
IUPAC Name (1S,2S)-2-[2-methoxy-4-[(E)-prop-1-enyl]phenoxy]-1-(3,4,5-trimethoxyphenyl)propan-1-ol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL464934
PubChem CID 10691693
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds

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 LNEPYGTUEWFPKT-XSPAYHLVSA-N
Standard InCHI InChI=1S/C22H28O6/c1-7-8-15-9-10-17(18(11-15)24-3)28-14(2)21(23)16-12-19(25-4)22(27-6)20(13-16)26-5/h7-14,21,23H,1-6H3/b8-7+/t14-,21+/m0/s1
SMILES C/C=C/c1ccc(c(c1)OC)O[C@H]([C@H](c1cc(OC)c(c(c1)OC)OC)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   388.19 Volume:   406.241
?
Van der Waals volume.
Dense:   0.956 LogP:   2.753
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.002
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.627
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The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   13.0
TPSA:   66.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.693 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.101 Fsp3:   0.364
MCE-18:   30.0
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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:   0.264 Fluc inhibitor:   0.828
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.125
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.241
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.336 Promiscuous compounds:   0.051

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.026 MDCK Permeability:   -4.725
Pgp-inhibitor:   0.464 Pgp-substrate:   0.013
PAMPA:   0.012
?
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%):   0.114 30% Bioavailability (F30%):   0.06
50% Bioavailability (F50%):   0.942

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.006 MRP1:   0.973
Plasma Protein Binding (PPB):   97.214% Volume Distribution (VD):   0.204
Fu: 2.29%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.99
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.787
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.283 CYP1A2-substrate:   0.089
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.396
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.094
CYP2D6-inhibitor:   0.202 CYP2D6-substrate:   0.335
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.928
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.771
?
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):  7.748 Half-life (T1/2):  1.07

ADMET: Toxicity

hERG Blockers:  0.283 hERG Blockers (10um):  0.656
Human Hepatotoxicity (H-HT):  0.62 Drug-induced Liver Injury (DILI):  0.297
AMES Toxicity:  0.284 Rat Oral Acute Toxicity:  0.246
Maximum Recommended Daily Dose:  0.507 Skin Sensitization:  0.372
Carcinogencity:  0.434 Eye Corrosion:  0.106
Eye Irritation:  0.787 Respiratory Toxicity:  0.669
Drug-induced Neurotoxicity:  0.624 Ototoxicity:  0.58
Hematotoxicity:  0.353 Drug-induced Nephrotoxicity:  0.641
Genotoxicity:  0.045 RPMI-8226 Immunitoxicity:  0.139
A549 Cytotoxicity:  0.136 Hek293 Cytotoxicity:  0.353
BCF:   2.074
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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:   3.717
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.762
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.865
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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
NPO12339 Daphne feddei Species Thymelaeaceae Eukaryota stem bark Kunming, Yunnan Province, China n.a. PMID[18986199]
NPO10211 Pajanelia multijuga n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO21329 Ilyonectria destructans Species Nectriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12339 Daphne feddei Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23754 Solanum aculeatissimum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2788 Virola surinamensis Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2788 Virola surinamensis Species Myristicaceae Eukaryota n.a. n.a. Database[FooDB]
NPO2788 Virola surinamensis Species Myristicaceae Eukaryota n.a. n.a. Database[FooDB]
NPO2788 Virola surinamensis Species Myristicaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO2788 Virola surinamensis Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23754 Solanum aculeatissimum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2788 Virola surinamensis Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[Title]
NPO21329 Ilyonectria destructans Species Nectriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2788 Virola surinamensis Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12339 Daphne feddei Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10211 Pajanelia multijuga n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO23754 Solanum aculeatissimum Species Solanaceae 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
NPT1819 Organism Microsporum canis Arthroderma otae MIC > 250.0 ug.mL-1 PMID[9249968]
NPT327 Organism Microsporum gypseum Microsporum gypseum MIC > 250.0 ug.mL-1 PMID[9249968]
NPT330 Organism Trichophyton mentagrophytes Trichophyton mentagrophytes MIC > 250.0 ug.mL-1 PMID[9249968]
NPT329 Organism Trichophyton rubrum Trichophyton rubrum MIC = 125.0 ug.mL-1 PMID[9249968]
NPT328 Organism Epidermophyton floccosum Epidermophyton floccosum MIC = 50.0 ug.mL-1 PMID[9249968]

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 NPC222004 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 NPC273295
1.0 High Similarity NPC602870
0.8444 Intermediate Similarity NPC94276
0.8444 Intermediate Similarity NPC109822
0.8444 Intermediate Similarity NPC605984
0.7556 Intermediate Similarity NPC218856
0.7556 Intermediate Similarity NPC210623
0.7556 Intermediate Similarity NPC226788
0.75 Intermediate Similarity NPC470258
0.7308 Intermediate Similarity NPC483401
0.6981 Remote Similarity NPC58607
0.6981 Remote Similarity NPC191037
0.6981 Remote Similarity NPC178284
0.6471 Remote Similarity NPC473091
0.6226 Remote Similarity NPC3439
0.6226 Remote Similarity NPC285339
0.6226 Remote Similarity NPC172818
0.5814 Remote Similarity NPC310905
0.5455 Remote Similarity NPC190629
0.5439 Remote Similarity NPC485478
0.5385 Remote Similarity NPC202582
0.5385 Remote Similarity NPC243749
0.537 Remote Similarity NPC473090
0.5319 Remote Similarity NPC245552
0.5116 Remote Similarity NPC203924

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC222004 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