Natural Product: NPC470132

Natural Product IDNPC470132
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (-)-Epi-Methylphelligrin A
IUPAC Name (2S)-5-hydroxy-2-(4-hydroxyphenyl)-6-[(2-hydroxyphenyl)methyl]-7-methoxy-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1780031
PubChem CID 53248706
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002650] Diarylheptanoids
        • [CHEMONTID:0002651] Linear diarylheptanoids

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 SCYWNQTZQMNLGR-IBGZPJMESA-N
Standard InCHI InChI=1S/C23H20O6/c1-28-20-12-21-22(23(27)16(20)10-14-4-2-3-5-17(14)25)18(26)11-19(29-21)13-6-8-15(24)9-7-13/h2-9,12,19,24-25,27H,10-11H2,1H3/t19-/m0/s1
SMILES COc1cc2O[C@@H](CC(=O)c2c(c1Cc1ccccc1O)O)c1ccc(cc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   392.13 Volume:   398.515
?
Van der Waals volume.
Dense:   0.984 LogP:   3.686
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.308
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.697
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   24.0
TPSA:   96.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.618 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.005 Fsp3:   0.174
MCE-18:   72.407
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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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.892 Fluc inhibitor:   0.655
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.379
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.594
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.193 Promiscuous compounds:   0.049

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.032 MDCK Permeability:   -4.797
Pgp-inhibitor:   0.987 Pgp-substrate:   0.047
PAMPA:   0.619
?
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%):   0.001 30% Bioavailability (F30%):   0.853
50% Bioavailability (F50%):   0.991

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.965
Plasma Protein Binding (PPB):   97.437% Volume Distribution (VD):   0.061
Fu: 2.355%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.966
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.993
BSEP inhibitor:   0.992

ADMET: Metabolism

CYP1A2-inhibitor:   0.594 CYP1A2-substrate:   0.374
CYP2C19-inhibitor:   0.086 CYP2C19-substrate:   0.939
CYP2C9-inhibitor:   0.956 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.932 CYP2D6-substrate:   0.496
CYP3A4-inhibitor:   0.882 CYP3A4-substrate:   0.584
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.25
HLM stability:   0.552
?
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):  6.066 Half-life (T1/2):  1.21

ADMET: Toxicity

hERG Blockers:  0.09 hERG Blockers (10um):  0.656
Human Hepatotoxicity (H-HT):  0.698 Drug-induced Liver Injury (DILI):  0.125
AMES Toxicity:  0.62 Rat Oral Acute Toxicity:  0.421
Maximum Recommended Daily Dose:  0.695 Skin Sensitization:  0.874
Carcinogencity:  0.432 Eye Corrosion:  0.008
Eye Irritation:  0.989 Respiratory Toxicity:  0.515
Drug-induced Neurotoxicity:  0.632 Ototoxicity:  0.267
Hematotoxicity:  0.093 Drug-induced Nephrotoxicity:  0.402
Genotoxicity:  0.905 RPMI-8226 Immunitoxicity:  0.164
A549 Cytotoxicity:  0.576 Hek293 Cytotoxicity:  0.797
BCF:   1.338
?
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:   4.34
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.383
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.829
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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
NPO32484 phellinus baumii Species Hymenochaetaceae Eukaryota n.a. n.a. n.a. PMID[20708931]
NPO32484 phellinus baumii Species Hymenochaetaceae Eukaryota n.a. n.a. n.a. PMID[21531558]
NPO32484 phellinus baumii Species Hymenochaetaceae Eukaryota n.a. n.a. n.a. PMID[26077494]
NPO32484 phellinus baumii Species Hymenochaetaceae 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
NPT2 Others Unspecified n.a. IC50 = 36440.0 nM PMID[17958396]

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 NPC470132 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 NPC470131
0.7333 Intermediate Similarity NPC470135
0.7049 Intermediate Similarity NPC470133
0.6613 Remote Similarity NPC3642
0.6452 Remote Similarity NPC39045
0.6379 Remote Similarity NPC329203
0.6379 Remote Similarity NPC222342
0.619 Remote Similarity NPC109183
0.6094 Remote Similarity NPC122894
0.6 Remote Similarity NPC475267
0.5846 Remote Similarity NPC69674
0.5833 Remote Similarity NPC324386
0.5672 Remote Similarity NPC486094
0.5667 Remote Similarity NPC150648
0.5593 Remote Similarity NPC225153
0.5593 Remote Similarity NPC479876
0.55 Remote Similarity NPC32441
0.55 Remote Similarity NPC79943
0.5484 Remote Similarity NPC606248
0.5342 Remote Similarity NPC78324
0.5342 Remote Similarity NPC115601
0.5342 Remote Similarity NPC39154
0.5342 Remote Similarity NPC208011
0.5246 Remote Similarity NPC6407
0.5246 Remote Similarity NPC545184
0.5238 Remote Similarity NPC485881
0.5238 Remote Similarity NPC469764
0.5238 Remote Similarity NPC210084
0.5161 Remote Similarity NPC312391
0.5079 Remote Similarity NPC300668
0.5079 Remote Similarity NPC482119
0.5079 Remote Similarity NPC480993
0.5079 Remote Similarity NPC482120
0.5067 Remote Similarity NPC472636

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC470132 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
0.55 Remote Similarity NPD1552 Clinical (unspecified phase)

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