Natural Product: NPC24673

Natural Product IDNPC24673
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Derrone
IUPAC Name 5-hydroxy-3-(4-hydroxyphenyl)-8,8-dimethylpyrano[2,3-h]chromen-4-one
Synonyms derrone
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL393223
PubChem CID 14704457
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0003530] Pyranoisoflavonoids

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 ZSYPWSSGRVZENH-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H16O5/c1-20(2)8-7-13-16(25-20)9-15(22)17-18(23)14(10-24-19(13)17)11-3-5-12(21)6-4-11/h3-10,21-22H,1-2H3
SMILES CC1(C)C=Cc2c(cc(c3c(=O)c(coc23)c2ccc(cc2)O)O)O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   336.1 Volume:   340.473
?
Van der Waals volume.
Dense:   0.987 LogP:   3.214
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.878
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.834
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   23.0
TPSA:   79.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.7 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.871 Fsp3:   0.15
MCE-18:   50.087
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.696 Fluc inhibitor:   0.848
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.869
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.717
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.41 Promiscuous compounds:   0.279

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.832 MDCK Permeability:   -4.704
Pgp-inhibitor:   0.293 Pgp-substrate:   0.046
PAMPA:   0.784
?
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):   0.003
20% Bioavailability (F20%):   0.861 30% Bioavailability (F30%):   0.977
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.147 MRP1:   0.718
Plasma Protein Binding (PPB):   97.474% Volume Distribution (VD):   0.091
Fu: 1.944%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.992
OATP1B3 inhibitor:   0.675 BCRP inhibitor:   0.862
BSEP inhibitor:   0.996

ADMET: Metabolism

CYP1A2-inhibitor:   0.096 CYP1A2-substrate:   0.989
CYP2C19-inhibitor:   0.021 CYP2C19-substrate:   0.241
CYP2C9-inhibitor:   0.985 CYP2C9-substrate:   0.403
CYP2D6-inhibitor:   0.669 CYP2D6-substrate:   0.281
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.004 CYP2C8-inhibitor:   0.932
HLM stability:   0.029
?
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):  5.849 Half-life (T1/2):  0.982

ADMET: Toxicity

hERG Blockers:  0.17 hERG Blockers (10um):  0.582
Human Hepatotoxicity (H-HT):  0.581 Drug-induced Liver Injury (DILI):  0.869
AMES Toxicity:  0.568 Rat Oral Acute Toxicity:  0.636
Maximum Recommended Daily Dose:  0.668 Skin Sensitization:  0.653
Carcinogencity:  0.734 Eye Corrosion:  0.01
Eye Irritation:  0.938 Respiratory Toxicity:  0.744
Drug-induced Neurotoxicity:  0.378 Ototoxicity:  0.31
Hematotoxicity:  0.186 Drug-induced Nephrotoxicity:  0.278
Genotoxicity:  0.811 RPMI-8226 Immunitoxicity:  0.07
A549 Cytotoxicity:  0.196 Hek293 Cytotoxicity:  0.568
BCF:   1.578
?
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:   4.436
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.593
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.103
?
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
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s40502-015-0143-x]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1093/pcp/pcg054]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1134/S1021443709050069]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota Leaves n.a. n.a. PMID[12713396]
NPO26058 Erycibe expansa Species Convolvulaceae Eukaryota n.a. stem n.a. PMID[17077549]
NPO26058 Erycibe expansa Species Convolvulaceae Eukaryota stems n.a. n.a. PMID[17158054]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota roots n.a. n.a. PMID[20022509]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21866899]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[23325115]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota Roots n.a. n.a. PMID[23541646]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[28140583]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[39683057]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[7381508]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4761 Derris robusta Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26058 Erycibe expansa Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26058 Erycibe expansa Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4761 Derris robusta Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26058 Erycibe expansa Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4761 Derris robusta Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO4761 Derris robusta Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29384 Glycyrrhiza glabra 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
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens Inhibition = 21.0 % PMID[28140583]
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens FC = 1.4 n.a. PMID[28140583]
NPT741 Individual protein Tyrosinase Homo sapiens Inhibition = 11.0 % PMID[28140583]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT466 Cell line U-937 Homo sapiens IC50 = 26000.0 nM PMID[17158054]
NPT466 Cell line U-937 Homo sapiens IC50 = 20000.0 nM PMID[17158054]
NPT466 Cell line U-937 Homo sapiens IC50 = 13000.0 nM PMID[17158054]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 0.0 % PMID[28140583]
NPT65 Cell line HepG2 Homo sapiens Inhibition = 23.7 % PMID[28140583]
NPT81 Cell line A549 Homo sapiens Inhibition = 0.0 % PMID[28140583]
NPT83 Cell line MCF7 Homo sapiens Inhibition = 13.6 % PMID[28140583]
NPT660 Cell line SW480 Homo sapiens Inhibition = 0.0 % PMID[28140583]
NPT188 Organism Candida parapsilosis Candida parapsilosis MIC = 7.81 ug.mL-1 PMID[31427220]
NPT20 Organism Candida albicans Candida albicans MIC = 7.81 ug.mL-1 PMID[31427220]

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 NPC24673 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
0.8254 Intermediate Similarity NPC15435
0.7391 Intermediate Similarity NPC604503
0.7302 Intermediate Similarity NPC600644
0.7164 Intermediate Similarity NPC261470
0.6479 Remote Similarity NPC201731
0.6418 Remote Similarity NPC97716
0.6324 Remote Similarity NPC293852
0.6232 Remote Similarity NPC166757
0.6143 Remote Similarity NPC6511
0.6056 Remote Similarity NPC51759
0.5972 Remote Similarity NPC237635
0.5946 Remote Similarity NPC50960
0.5833 Remote Similarity NPC471984
0.5658 Remote Similarity NPC79469
0.5658 Remote Similarity NPC282307
0.5652 Remote Similarity NPC607923
0.5634 Remote Similarity NPC120105
0.5616 Remote Similarity NPC474052
0.5556 Remote Similarity NPC170492
0.5541 Remote Similarity NPC107838
0.5507 Remote Similarity NPC242100
0.5455 Remote Similarity NPC303644
0.5443 Remote Similarity NPC470681
0.5443 Remote Similarity NPC91701
0.5417 Remote Similarity NPC275122
0.5417 Remote Similarity NPC55662
0.5417 Remote Similarity NPC5322
0.5373 Remote Similarity NPC483565
0.5333 Remote Similarity NPC84124
0.5286 Remote Similarity NPC144118
0.5278 Remote Similarity NPC211811
0.527 Remote Similarity NPC113055
0.525 Remote Similarity NPC189087
0.525 Remote Similarity NPC62840
0.525 Remote Similarity NPC603859
0.52 Remote Similarity NPC608710
0.5195 Remote Similarity NPC170026
0.5152 Remote Similarity NPC295384
0.5139 Remote Similarity NPC222298
0.5139 Remote Similarity NPC604003
0.5135 Remote Similarity NPC128961
0.5132 Remote Similarity NPC231763
0.5128 Remote Similarity NPC95842
0.5128 Remote Similarity NPC484043
0.5128 Remote Similarity NPC484044
0.5125 Remote Similarity NPC40037
0.5125 Remote Similarity NPC188403
0.5122 Remote Similarity NPC217083
0.5122 Remote Similarity NPC478514
0.5075 Remote Similarity NPC131266
0.5067 Remote Similarity NPC57393
0.5065 Remote Similarity NPC104406

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC24673 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
NPD

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