Natural Product: NPC494392

Natural Product IDNPC494392
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2-[4-[4-(5,7-dihydroxy-4-oxo-chromen-2-yl)-2-hydroxy-phenoxy]phenyl]-5,7-dihydroxy-chromen-4-one
IUPAC Name 2-[4-[4-(5,7-dihydroxy-4-oxo-chromen-2-yl)-2-hydroxy-phenoxy]phenyl]-5,7-dihydroxy-chromen-4-one
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 MNTSOBLYWJLVEK-UHFFFAOYSA-N
Standard InCHI InChI=1S/C30H18O10/c31-16-8-20(34)29-22(36)12-25(39-27(29)10-16)14-1-4-18(5-2-14)38-24-6-3-15(7-19(24)33)26-13-23(37)30-21(35)9-17(32)11-28(30)40-26/h1-13,31-35H
SMILES O=C1C=C(C2=CC=C(OC3=CC=C(C4=CC(=O)C5=C(O)C=C(O)C=C5O4)C=C3O)C=C2)OC2=CC(O)=CC(O)=C12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   538.09 Volume:   521.816
?
Van der Waals volume.
Dense:   1.031 LogP:   4.825
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.935
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -6.302
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   36.0
TPSA:   170.8
?
Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   5.0 Rings:   6.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.192 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.917 Fsp3:   0.0
MCE-18:   35.0
?
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:   Accepted
Golden Triangle Rule:   Accepted BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.998 Fluc inhibitor:   0.785
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.946
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.989
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.625 Promiscuous compounds:   0.848

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.342 MDCK Permeability:   -4.8
Pgp-inhibitor:   0.002 Pgp-substrate:   0.494
PAMPA:   0.607
?
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):   0.001
20% Bioavailability (F20%):   0.61 30% Bioavailability (F30%):   0.981
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.89
Plasma Protein Binding (PPB):   95.98% Volume Distribution (VD):   -0.285
Fu: 4.252%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.763
OATP1B3 inhibitor:   0.992 BCRP inhibitor:   0.989
BSEP inhibitor:   0.943

ADMET: Metabolism

CYP1A2-inhibitor:   0.859 CYP1A2-substrate:   0.023
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.993 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.7
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.89
?
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):  1.921 Half-life (T1/2):  1.77

ADMET: Toxicity

hERG Blockers:  0.135 hERG Blockers (10um):  0.63
Human Hepatotoxicity (H-HT):  0.439 Drug-induced Liver Injury (DILI):  0.988
AMES Toxicity:  0.827 Rat Oral Acute Toxicity:  0.546
Maximum Recommended Daily Dose:  0.988 Skin Sensitization:  0.366
Carcinogencity:  0.914 Eye Corrosion:  0.004
Eye Irritation:  0.999 Respiratory Toxicity:  0.909
Drug-induced Neurotoxicity:  0.003 Ototoxicity:  0.048
Hematotoxicity:  0.018 Drug-induced Nephrotoxicity:  0.006
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.069
A549 Cytotoxicity:  0.765 Hek293 Cytotoxicity:  0.985
BCF:   1.239
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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:   4.616
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.096
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.897
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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
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flowers n.a. n.a. DOI[10.1002/elan.200403102]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flowers n.a. n.a. DOI[10.1016/j.foodchem.2012.02.124]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flowers n.a. n.a. PMID[11077184]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flowers n.a. n.a. PMID[17328234]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flower buds n.a. n.a. PMID[18321056]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. flower n.a. PMID[21804227]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. flower bud n.a. PMID[21942812]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota flower buds Henan province, China 2005-MAY PMID[21942812]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. leaf n.a. PMID[23265495]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flower buds n.a. n.a. PMID[24279769]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO1515 Lonicera japonica Species Caprifoliaceae 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

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 NPC494392 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
0.7966 Intermediate Similarity NPC112954
0.7241 Intermediate Similarity NPC52005
0.7143 Intermediate Similarity NPC34089
0.7143 Intermediate Similarity NPC196179
0.6875 Remote Similarity NPC183
0.6724 Remote Similarity NPC231772
0.6607 Remote Similarity NPC279121
0.6545 Remote Similarity NPC50898
0.6545 Remote Similarity NPC78540
0.6441 Remote Similarity NPC601901
0.6286 Remote Similarity NPC272064
0.614 Remote Similarity NPC175013
0.6129 Remote Similarity NPC12200
0.6129 Remote Similarity NPC606638
0.5846 Remote Similarity NPC605634
0.5781 Remote Similarity NPC183950
0.5667 Remote Similarity NPC213216
0.5645 Remote Similarity NPC62536
0.5645 Remote Similarity NPC120464
0.5645 Remote Similarity NPC483773
0.55 Remote Similarity NPC274121
0.5455 Remote Similarity NPC191306
0.5342 Remote Similarity NPC150908
0.5323 Remote Similarity NPC610974
0.5312 Remote Similarity NPC256283
0.527 Remote Similarity NPC71061
0.527 Remote Similarity NPC72425
0.527 Remote Similarity NPC303485
0.5231 Remote Similarity NPC82325
0.5231 Remote Similarity NPC54394
0.5217 Remote Similarity NPC138299
0.5217 Remote Similarity NPC111112
0.5211 Remote Similarity NPC254351
0.5205 Remote Similarity NPC134796
0.52 Remote Similarity NPC186227
0.5185 Remote Similarity NPC600989
0.5176 Remote Similarity NPC219927
0.5176 Remote Similarity NPC611172
0.5152 Remote Similarity NPC223579
0.5152 Remote Similarity NPC607642
0.5139 Remote Similarity NPC603692
0.5139 Remote Similarity NPC610480
0.5132 Remote Similarity NPC215203
0.5132 Remote Similarity NPC143851
0.5077 Remote Similarity NPC600900
0.5065 Remote Similarity NPC601565

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC494392 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
0.6607 Remote Similarity NPD1511 Phase 2

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