Natural Product: NPC212015

Natural Product IDNPC212015
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4-[(1S)-1-Hydroxy-3-(4-Hydroxy-3-Methoxyphenyl)Propyl]Benzene-1,3-Diol
IUPAC Name 4-[(1S)-1-hydroxy-3-(4-hydroxy-3-methoxyphenyl)propyl]benzene-1,3-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1909924
PubChem CID 57392813
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003467] Linear 1,3-diarylpropanoids
        • [CHEMONTID:0003496] Cinnamylphenols

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 LJNAUACHFOSZRS-ZDUSSCGKSA-N
Standard InCHI InChI=1S/C16H18O5/c1-21-16-8-10(3-7-14(16)19)2-6-13(18)12-5-4-11(17)9-15(12)20/h3-5,7-9,13,17-20H,2,6H2,1H3/t13-/m0/s1
SMILES COc1cc(CC[C@@H](c2ccc(cc2O)O)O)ccc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   290.12 Volume:   296.312
?
Van der Waals volume.
Dense:   0.979 LogP:   1.432
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.664
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.224
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   12.0
TPSA:   90.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.679 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.627 Fsp3:   0.25
MCE-18:   26.0
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.58 Fluc inhibitor:   0.459
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.019
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.105
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.464 Promiscuous compounds:   0.488

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.069 MDCK Permeability:   -4.841
Pgp-inhibitor:   0.131 Pgp-substrate:   0.541
PAMPA:   0.137
?
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):   0.01
20% Bioavailability (F20%):   0.595 30% Bioavailability (F30%):   0.869
50% Bioavailability (F50%):   0.99

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.542
Plasma Protein Binding (PPB):   90.921% Volume Distribution (VD):   -0.332
Fu: 10.096%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.974
OATP1B3 inhibitor:   0.966 BCRP inhibitor:   0.529
BSEP inhibitor:   0.45

ADMET: Metabolism

CYP1A2-inhibitor:   0.891 CYP1A2-substrate:   0.064
CYP2C19-inhibitor:   0.982 CYP2C19-substrate:   0.919
CYP2C9-inhibitor:   0.978 CYP2C9-substrate:   0.1
CYP2D6-inhibitor:   0.687 CYP2D6-substrate:   0.92
CYP3A4-inhibitor:   0.304 CYP3A4-substrate:   0.963
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.902
?
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):  6.722 Half-life (T1/2):  1.942

ADMET: Toxicity

hERG Blockers:  0.217 hERG Blockers (10um):  0.64
Human Hepatotoxicity (H-HT):  0.632 Drug-induced Liver Injury (DILI):  0.033
AMES Toxicity:  0.401 Rat Oral Acute Toxicity:  0.216
Maximum Recommended Daily Dose:  0.691 Skin Sensitization:  0.883
Carcinogencity:  0.242 Eye Corrosion:  0.042
Eye Irritation:  0.971 Respiratory Toxicity:  0.713
Drug-induced Neurotoxicity:  0.212 Ototoxicity:  0.324
Hematotoxicity:  0.057 Drug-induced Nephrotoxicity:  0.207
Genotoxicity:  0.686 RPMI-8226 Immunitoxicity:  0.1
A549 Cytotoxicity:  0.756 Hek293 Cytotoxicity:  0.733
BCF:   0.935
?
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:   3.484
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.493
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.886
?
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
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota seeds n.a. n.a. PMID[17998162]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[1955885]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. fruit n.a. PMID[20879744]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[27419473]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[32515616]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[33444950]
NPO7237 Xanthostemon oppositifolius Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2665 Andinobates fulguritus Species Dendrobatidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8303 Catalpa bignonioides Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17811 Cephalonoplos segetum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5162 Comaster multifida Species Comatulidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8532 Helipterum tenellum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5334 Rhodotypos scandens Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6113 Piper pedicellosum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5746 Pancratium trianthum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO490 Lophozonia menziesii Species Nothofagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28409 Lens phaseoloides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19928 Lachnoanaerobaculum saburreum Species Lachnospiraceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO4539 Ipomoea cristulata Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1382 Hyptis tomentosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7393 Esenbeckia nesiotica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Leaf Essent. Oil n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Bark n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Aril n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. Database[FooDB]
NPO1382 Hyptis tomentosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8303 Catalpa bignonioides Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO1382 Hyptis tomentosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8303 Catalpa bignonioides Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1382 Hyptis tomentosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[Title]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7237 Xanthostemon oppositifolius Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28409 Lens phaseoloides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8532 Helipterum tenellum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1382 Hyptis tomentosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6113 Piper pedicellosum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5162 Comaster multifida Species Comatulidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19928 Lachnoanaerobaculum saburreum Species Lachnospiraceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO4539 Ipomoea cristulata Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO490 Lophozonia menziesii Species Nothofagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17811 Cephalonoplos segetum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5746 Pancratium trianthum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7393 Esenbeckia nesiotica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5334 Rhodotypos scandens Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2665 Andinobates fulguritus Species Dendrobatidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8303 Catalpa bignonioides Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5241 Myristica fragrans Species Myristicaceae 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
NPT113 Cell line RAW264.7 Mus musculus IC50 > 50000.0 nM PMID[21978676]

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 NPC212015 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
0.6226 Remote Similarity NPC112237
0.6136 Remote Similarity NPC8547
0.5882 Remote Similarity NPC473853
0.5882 Remote Similarity NPC470212
0.5741 Remote Similarity NPC481913
0.5714 Remote Similarity NPC312675
0.5714 Remote Similarity NPC262156
0.5714 Remote Similarity NPC184651
0.5714 Remote Similarity NPC113865
0.5625 Remote Similarity NPC17943
0.5625 Remote Similarity NPC299406
0.5577 Remote Similarity NPC481914
0.549 Remote Similarity NPC82679
0.5455 Remote Similarity NPC156840
0.5439 Remote Similarity NPC215941
0.5439 Remote Similarity NPC123196
0.5439 Remote Similarity NPC311419
0.5435 Remote Similarity NPC221049
0.5435 Remote Similarity NPC140359
0.54 Remote Similarity NPC177291
0.54 Remote Similarity NPC127937
0.537 Remote Similarity NPC343720
0.537 Remote Similarity NPC54872
0.5319 Remote Similarity NPC471693
0.5306 Remote Similarity NPC197757
0.5283 Remote Similarity NPC98631
0.5283 Remote Similarity NPC206615
0.5283 Remote Similarity NPC74817
0.5273 Remote Similarity NPC137427
0.5263 Remote Similarity NPC310718
0.5217 Remote Similarity NPC257124
0.5208 Remote Similarity NPC255675
0.5192 Remote Similarity NPC51840
0.5185 Remote Similarity NPC324571
0.5179 Remote Similarity NPC123228
0.5179 Remote Similarity NPC123722
0.5102 Remote Similarity NPC85488
0.5091 Remote Similarity NPC164386
0.5091 Remote Similarity NPC303680
0.5088 Remote Similarity NPC257589

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC212015 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
0.5217 Remote Similarity NPD228 Phase 0

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