Natural Product: NPC490410

Natural Product IDNPC490410
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Theaflagallin
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000123] Benzopyrans
        • [CHEMONTID:0003410] 1-benzopyrans

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 KOXRJHMEFYNYME-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H16O9/c21-9-4-11(22)10-6-14(25)20(29-15(10)5-9)8-1-7-2-13(24)18(27)19(28)16(7)17(26)12(23)3-8/h1-5,14,20-22,24-25,27-28H,6H2,(H,23,26)
SMILES OC1CC2=C(O)C=C(O)C=C2OC1C1=CC(=O)C(O)=C2C(O)=C(O)C(O)=CC2=C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   400.08 Volume:   375.634
?
Van der Waals volume.
Dense:   1.065 LogP:   0.413
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.639
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.308
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   24.0
TPSA:   167.91
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   7.0 Rings:   4.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.299 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.861 Fsp3:   0.15
MCE-18:   84.783
?
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:   1
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.84 Fluc inhibitor:   0.121
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.682
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.586
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.538 Promiscuous compounds:   0.717

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.627 MDCK Permeability:   -4.968
Pgp-inhibitor:   0.0 Pgp-substrate:   0.261
PAMPA:   0.993
?
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):   0.177
20% Bioavailability (F20%):   0.753 30% Bioavailability (F30%):   0.989
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.979
Plasma Protein Binding (PPB):   92.508% Volume Distribution (VD):   -0.034
Fu: 10.374%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.556
OATP1B3 inhibitor:   0.99 BCRP inhibitor:   0.058
BSEP inhibitor:   0.006

ADMET: Metabolism

CYP1A2-inhibitor:   0.153 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.237 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.744 CYP2D6-substrate:   0.041
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.484
HLM stability:   0.101
?
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):  5.568 Half-life (T1/2):  2.365

ADMET: Toxicity

hERG Blockers:  0.041 hERG Blockers (10um):  0.682
Human Hepatotoxicity (H-HT):  0.463 Drug-induced Liver Injury (DILI):  0.257
AMES Toxicity:  0.717 Rat Oral Acute Toxicity:  0.528
Maximum Recommended Daily Dose:  0.943 Skin Sensitization:  0.941
Carcinogencity:  0.298 Eye Corrosion:  0.0
Eye Irritation:  0.841 Respiratory Toxicity:  0.763
Drug-induced Neurotoxicity:  0.017 Ototoxicity:  0.875
Hematotoxicity:  0.035 Drug-induced Nephrotoxicity:  0.115
Genotoxicity:  0.999 RPMI-8226 Immunitoxicity:  0.066
A549 Cytotoxicity:  0.952 Hek293 Cytotoxicity:  0.874
BCF:   0.656
?
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:   3.307
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.329
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.858
?
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
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. PMID[ 16712885]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.foodchem.2013.08.121]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Flowers n.a. n.a. PMID[16180814]
NPO8258 Camellia sinensis Species Theaceae Eukaryota seeds Shizuoka prefecture, Japan n.a. PMID[16499314]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. PMID[18068204]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. PMID[21434603]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. flower n.a. PMID[21922925]
NPO8258 Camellia sinensis Species Theaceae Eukaryota flower buds n.a. n.a. PMID[21925888]
NPO8258 Camellia sinensis Species Theaceae Eukaryota leaves n.a. n.a. PMID[22377672]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. leaf n.a. PMID[23265489]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Leaves Bandung, West Java, Indonesia PMID[23621359]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. PMID[37255739]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Stem n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Seed Oil n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Leaf Essent. Oil n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Cotyledon n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8258 Camellia sinensis Species Theaceae 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
NPO8258 Camellia sinensis Tea Or Coffee Leaf 0.35 0.3 0.4 mg/100g Database [DUKE]

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 NPC490410 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
0.6 Remote Similarity NPC268266
0.6 Remote Similarity NPC42760
0.6 Remote Similarity NPC220825
0.6 Remote Similarity NPC268342
0.5634 Remote Similarity NPC607430
0.5556 Remote Similarity NPC261619
0.5556 Remote Similarity NPC61477
0.5556 Remote Similarity NPC47398
0.5556 Remote Similarity NPC78770
0.5556 Remote Similarity NPC234333
0.5556 Remote Similarity NPC219876
0.5556 Remote Similarity NPC126029
0.5556 Remote Similarity NPC15658
0.5556 Remote Similarity NPC260898
0.5484 Remote Similarity NPC207179
0.5484 Remote Similarity NPC167571
0.5484 Remote Similarity NPC278552
0.5417 Remote Similarity NPC9636
0.5373 Remote Similarity NPC16435
0.5303 Remote Similarity NPC61946
0.52 Remote Similarity NPC308402

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC490410 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
0.6173 Remote Similarity NPD7993 Clinical (unspecified phase)
0.5556 Remote Similarity NPD1612 Clinical (unspecified phase)
0.5556 Remote Similarity NPD1613 Phase 4

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