Natural Product: NPC285973

Natural Product IDNPC285973
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 9-Hydroxy-7-(4-Hydroxyphenyl)-[1,3]Dioxolo[4,5-G]Chromen-8-One
IUPAC Name 9-hydroxy-7-(4-hydroxyphenyl)-[1,3]dioxolo[4,5-g]chromen-8-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3527329
PubChem CID 5281779
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002901] Isoflav-2-enes
          • [CHEMONTID:0000494] Isoflavones

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 NUGRQNBDTZWXTP-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H10O6/c17-9-3-1-8(2-4-9)10-6-20-11-5-12-16(22-7-21-12)15(19)13(11)14(10)18/h1-6,17,19H,7H2
SMILES c1cc(ccc1c1coc2cc3c(c(c2c1=O)O)OCO3)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   298.05 Volume:   282.716
?
Van der Waals volume.
Dense:   1.054 LogP:   2.456
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.389
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.546
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   22.0
TPSA:   89.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.718 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.577 Fsp3:   0.062
MCE-18:   44.471
?
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:   0.633 Fluc inhibitor:   0.97
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.914
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.537
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.314 Promiscuous compounds:   0.428

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.931 MDCK Permeability:   -4.754
Pgp-inhibitor:   0.043 Pgp-substrate:   0.088
PAMPA:   0.928
?
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%):   0.216 30% Bioavailability (F30%):   0.084
50% Bioavailability (F50%):   0.816

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.183 MRP1:   0.546
Plasma Protein Binding (PPB):   95.94% Volume Distribution (VD):   -0.401
Fu: 4.776%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.652
OATP1B3 inhibitor:   0.469 BCRP inhibitor:   0.322
BSEP inhibitor:   0.931

ADMET: Metabolism

CYP1A2-inhibitor:   0.977 CYP1A2-substrate:   0.889
CYP2C19-inhibitor:   0.011 CYP2C19-substrate:   0.599
CYP2C9-inhibitor:   0.995 CYP2C9-substrate:   0.991
CYP2D6-inhibitor:   0.994 CYP2D6-substrate:   0.961
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.011 CYP2C8-inhibitor:   0.287
HLM stability:   0.014
?
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):  5.547 Half-life (T1/2):  0.857

ADMET: Toxicity

hERG Blockers:  0.156 hERG Blockers (10um):  0.535
Human Hepatotoxicity (H-HT):  0.535 Drug-induced Liver Injury (DILI):  0.787
AMES Toxicity:  0.526 Rat Oral Acute Toxicity:  0.566
Maximum Recommended Daily Dose:  0.707 Skin Sensitization:  0.449
Carcinogencity:  0.821 Eye Corrosion:  0.05
Eye Irritation:  0.969 Respiratory Toxicity:  0.664
Drug-induced Neurotoxicity:  0.448 Ototoxicity:  0.239
Hematotoxicity:  0.215 Drug-induced Nephrotoxicity:  0.272
Genotoxicity:  0.896 RPMI-8226 Immunitoxicity:  0.076
A549 Cytotoxicity:  0.208 Hek293 Cytotoxicity:  0.553
BCF:   1.251
?
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:   3.809
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.694
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.244
?
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
NPO22104 Trifolium pratense Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0031-9422(00)94679-X]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[10075762]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[11599360]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[19299148]
NPO28689 Armillaria mellea Species Physalacriaceae Eukaryota n.a. n.a. n.a. PMID[19795841]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. seed n.a. PMID[21381697]
NPO7528 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[21465599]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. rhizome n.a. PMID[22388969]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[24433009]
NPO7528 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[25036154]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. rhizome n.a. PMID[25204177]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[28032759]
NPO22104 Trifolium pratense Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[30199256]
NPO7528 Belamcanda chinensis Species Iridaceae Eukaryota Rhizomes n.a. n.a. PMID[31246464]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[37120447]
NPO28689 Armillaria mellea Species Physalacriaceae Eukaryota n.a. n.a. n.a. PMID[4040154]
NPO22104 Trifolium pratense Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28689 Armillaria mellea Species Physalacriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22104 Trifolium pratense Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO28689 Armillaria mellea Species Physalacriaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7528 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22104 Trifolium pratense Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO22104 Trifolium pratense Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7528 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7528 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28672 Ficus cunia Species Ficidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28328 Cortispongilla barroisi Species Malawispongiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28624 Canthium gilfillanii Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28647 Fleischmannia deborabellae Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28761 Tricholoma populinum Species Tricholomataceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28689 Armillaria mellea Species Physalacriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22104 Trifolium pratense Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29071 Anacardium giganteum Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22882 Biancaea millettii Species Fabaceae 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
NPT108 Individual protein Estrogen receptor alpha Homo sapiens FC = 4.0 n.a. PMID[34813298]
NPT108 Individual protein Estrogen receptor alpha Homo sapiens Activity n.a. n.a. n.a. PMID[34813298]
NPT249 Individual protein Glucocorticoid receptor Homo sapiens Activity n.a. n.a. n.a. PMID[34813298]
NPT249 Individual protein Glucocorticoid receptor Homo sapiens FC = 44.0 n.a. PMID[34813298]
NPT108 Individual protein Estrogen receptor alpha Homo sapiens FC = 1.07 n.a. PMID[34813298]
NPT249 Individual protein Glucocorticoid receptor Homo sapiens FC = 1.2 n.a. PMID[34813298]
NPT703 Individual protein UDP-glucuronosyltransferase 1-9 Homo sapiens Ki = 534000.0 nM PMID[21177485]
NPT695 Individual protein UDP-glucuronosyltransferase 1-8 Homo sapiens Ki = 22600.0 nM PMID[21177485]
NPT695 Individual protein UDP-glucuronosyltransferase 1-8 Homo sapiens Ki = 23400.0 nM PMID[21177485]
NPT542 Individual protein Progesterone receptor Homo sapiens FC = 48.4 n.a. PMID[30199256]
NPT542 Individual protein Progesterone receptor Homo sapiens Activity = 138.0 % PMID[30199256]
NPT542 Individual protein Progesterone receptor Homo sapiens Activity = 151.0 % PMID[30199256]
NPT901 Individual protein UDP-glucuronosyltransferase 1-1 Homo sapiens Ki = 8500.0 nM PMID[21177485]
NPT901 Individual protein UDP-glucuronosyltransferase 1-1 Homo sapiens Ki = 14100.0 nM PMID[21177485]
NPT903 Individual protein UDP-glucuronosyltransferase 1-7 Homo sapiens Ki = 101000.0 nM PMID[21177485]
NPT699 Individual protein UDP-glucuronosyltransferase 1-10 Homo sapiens Ki = 121300.0 nM PMID[21177485]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2738 Cell line Ishikawa Homo sapiens FC = 38.0 n.a. PMID[34813298]
NPT382 Cell line OVCAR-5 Homo sapiens Inhibition n.a. n.a. % PMID[34813298]
NPT382 Cell line OVCAR-5 Homo sapiens Inhibition = 22.0 % PMID[34813298]
NPT2738 Cell line Ishikawa Homo sapiens FC = 5.8 n.a. PMID[34813298]
NPT587 Tissue Liver microsome Rattus norvegicus Ki = 65300.0 nM PMID[21177485]
NPT587 Tissue Liver microsome Rattus norvegicus Ki = 44700.0 nM PMID[21177485]
NPT28438 Unchecked Unchecked n.a. Activity n.a. n.a. n.a. PMID[34813298]
NPT28438 Unchecked Unchecked n.a. Activity = 0.93 % PMID[34813298]
NPT28438 Unchecked Unchecked n.a. FC = 30.0 n.a. PMID[34813298]
NPT28438 Unchecked Unchecked n.a. Inhibition n.a. n.a. % PMID[34813298]
NPT28438 Unchecked Unchecked n.a. Activity = 18.4 % PMID[34813298]
NPT626 Tissue Liver microsome Homo sapiens Ki = 96900.0 nM PMID[21177485]
NPT626 Tissue Liver microsome Homo sapiens Ki = 50900.0 nM PMID[21177485]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus Activity n.a. n.a. n.a. PMID[34813298]





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference
Rattus norvegicus Liver CL = 51000.0 mL.min-1.g-1 PMID[21177485]
Homo sapiens Liver CL = 48500.0 mL.min-1.g-1 PMID[21177485]





 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 NPC285973 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
0.7818 Intermediate Similarity NPC216769
0.7333 Intermediate Similarity NPC225624
0.6825 Remote Similarity NPC295009
0.6508 Remote Similarity NPC62518
0.6167 Remote Similarity NPC269451
0.6066 Remote Similarity NPC303644
0.6 Remote Similarity NPC605229
0.5763 Remote Similarity NPC288316
0.5733 Remote Similarity NPC205076
0.5556 Remote Similarity NPC181124
0.5429 Remote Similarity NPC168085
0.5373 Remote Similarity NPC104728
0.5362 Remote Similarity NPC97716
0.5333 Remote Similarity NPC39426
0.5312 Remote Similarity NPC162680
0.5312 Remote Similarity NPC100971
0.5286 Remote Similarity NPC219917
0.5231 Remote Similarity NPC483565
0.5161 Remote Similarity NPC18954
0.5156 Remote Similarity NPC131266
0.5156 Remote Similarity NPC7013
0.5147 Remote Similarity NPC35544
0.5077 Remote Similarity NPC245382
0.5077 Remote Similarity NPC162668

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC285973 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
0.5333 Remote Similarity NPD1510 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