Natural Product: NPC596684

Natural Product IDNPC596684
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4'-O-Methylcatechin
IUPAC Name (2~{R},3~{S})-2-(3-hydroxy-4-methoxy-phenyl)chromane-3,5,7-triol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic 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 ZHDMPVIDHWJGTN-XJKSGUPXSA-N
Standard InCHI InChI=1S/C16H16O6/c1-21-14-3-2-8(4-12(14)19)16-13(20)7-10-11(18)5-9(17)6-15(10)22-16/h2-6,13,16-20H,7H2,1H3/t13-,16+/m0/s1
SMILES COC1=CC=C([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)C=C1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   304.09 Volume:   296.545
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Van der Waals volume.
Dense:   1.025 LogP:   1.18
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.61
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.499
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   17.0
TPSA:   99.38
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.676 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.257 Fsp3:   0.25
MCE-18:   59.4
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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:   1 PAINS Alert:   0
Colloidal aggregators:   0.554 Fluc inhibitor:   0.596
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.15
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.284
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.262 Promiscuous compounds:   0.162

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.881 MDCK Permeability:   -5.029
Pgp-inhibitor:   0.014 Pgp-substrate:   0.143
PAMPA:   0.125
?
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):   0.004
20% Bioavailability (F20%):   0.251 30% Bioavailability (F30%):   0.894
50% Bioavailability (F50%):   0.987

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.049 MRP1:   0.685
Plasma Protein Binding (PPB):   94.756% Volume Distribution (VD):   -0.098
Fu: 5.037%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.909
OATP1B3 inhibitor:   0.976 BCRP inhibitor:   0.087
BSEP inhibitor:   0.056

ADMET: Metabolism

CYP1A2-inhibitor:   0.995 CYP1A2-substrate:   0.023
CYP2C19-inhibitor:   0.155 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.818 CYP2C9-substrate:   0.071
CYP2D6-inhibitor:   0.79 CYP2D6-substrate:   0.038
CYP3A4-inhibitor:   0.997 CYP3A4-substrate:   0.581
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.555
HLM stability:   0.015
?
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):  6.954 Half-life (T1/2):  2.248

ADMET: Toxicity

hERG Blockers:  0.101 hERG Blockers (10um):  0.586
Human Hepatotoxicity (H-HT):  0.683 Drug-induced Liver Injury (DILI):  0.461
AMES Toxicity:  0.636 Rat Oral Acute Toxicity:  0.534
Maximum Recommended Daily Dose:  0.749 Skin Sensitization:  0.806
Carcinogencity:  0.534 Eye Corrosion:  0.006
Eye Irritation:  0.969 Respiratory Toxicity:  0.856
Drug-induced Neurotoxicity:  0.494 Ototoxicity:  0.301
Hematotoxicity:  0.158 Drug-induced Nephrotoxicity:  0.408
Genotoxicity:  0.843 RPMI-8226 Immunitoxicity:  0.13
A549 Cytotoxicity:  0.735 Hek293 Cytotoxicity:  0.739
BCF:   0.551
?
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:   2.873
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.232
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.436
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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
NPO31458 Cinnamomum cassia Species Lauraceae Eukaryota twigs n.a. n.a. PMID[19555125]
NPO31458 Cinnamomum cassia Species Lauraceae Eukaryota twigs n.a. n.a. PMID[22677314]
NPO31458 Cinnamomum cassia Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[34332066]
NPO31458 Cinnamomum cassia Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[37446712]
NPO31458 Cinnamomum cassia Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[38688144]
NPO31458 Cinnamomum cassia Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO31458 Cinnamomum cassia Species Lauraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO31458 Cinnamomum cassia Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]

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

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 NPC596684 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
0.7755 Intermediate Similarity NPC47398
0.7755 Intermediate Similarity NPC234333
0.7755 Intermediate Similarity NPC260898
0.7647 Intermediate Similarity NPC61946
0.7358 Intermediate Similarity NPC16435
0.7241 Intermediate Similarity NPC9636
0.7059 Intermediate Similarity NPC261619
0.7059 Intermediate Similarity NPC61477
0.7059 Intermediate Similarity NPC78770
0.7059 Intermediate Similarity NPC219876
0.7059 Intermediate Similarity NPC126029
0.7059 Intermediate Similarity NPC15658
0.7 Intermediate Similarity NPC207179
0.7 Intermediate Similarity NPC167571
0.7 Intermediate Similarity NPC278552
0.6727 Remote Similarity NPC320825
0.6667 Remote Similarity NPC268266
0.6667 Remote Similarity NPC42760
0.6667 Remote Similarity NPC220825
0.6667 Remote Similarity NPC268342
0.6429 Remote Similarity NPC171932
0.5846 Remote Similarity NPC308402
0.5606 Remote Similarity NPC28440
0.5593 Remote Similarity NPC471515
0.5429 Remote Similarity NPC278548
0.5424 Remote Similarity NPC302950
0.5362 Remote Similarity NPC211561
0.5254 Remote Similarity NPC250922
0.5152 Remote Similarity NPC58190
0.5152 Remote Similarity NPC108811
0.5152 Remote Similarity NPC170103
0.5152 Remote Similarity NPC236202
0.5152 Remote Similarity NPC262911
0.5152 Remote Similarity NPC202742
0.5152 Remote Similarity NPC607430
0.5085 Remote Similarity NPC44721
0.5085 Remote Similarity NPC211466
0.5085 Remote Similarity NPC605332
0.5075 Remote Similarity NPC246202
0.5075 Remote Similarity NPC224161
0.5075 Remote Similarity NPC46335
0.5075 Remote Similarity NPC294558
0.5075 Remote Similarity NPC18185
0.5075 Remote Similarity NPC263940
0.5075 Remote Similarity NPC279406
0.5075 Remote Similarity NPC486519

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC596684 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
0.7059 Intermediate Similarity NPD1612 Clinical (unspecified phase)
0.7059 Intermediate Similarity NPD1613 Phase 4
0.5424 Remote Similarity NPD1934 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