Natural Product: NPC474052

Natural Product IDNPC474052
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Isoderrone
IUPAC Name 3-(2,2-dimethylchromen-7-yl)-5,7-dihydroxychromen-4-one
Synonyms Isoderrone
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL459201
PubChem CID 44559672
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 CZOGIPODZHBTGK-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H16O5/c1-20(2)6-5-11-3-4-12(7-16(11)25-20)14-10-24-17-9-13(21)8-15(22)18(17)19(14)23/h3-10,21-22H,1-2H3
SMILES CC1(C=CC2=C(O1)C=C(C=C2)C3=COC4=CC(=CC(=C4C3=O)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   336.1 Volume:   340.473
?
Van der Waals volume.
Dense:   0.987 LogP:   3.472
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.797
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.733
?
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:   2.869 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:   0.764 Fluc inhibitor:   0.938
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.852
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.781
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.439 Promiscuous compounds:   0.308

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.044 MDCK Permeability:   -4.781
Pgp-inhibitor:   0.499 Pgp-substrate:   0.15
PAMPA:   0.354
?
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%):   0.648 30% Bioavailability (F30%):   0.971
50% Bioavailability (F50%):   0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.033 MRP1:   0.497
Plasma Protein Binding (PPB):   97.655% Volume Distribution (VD):   0.15
Fu: 2.043%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.972
OATP1B3 inhibitor:   0.95 BCRP inhibitor:   0.996
BSEP inhibitor:   0.987

ADMET: Metabolism

CYP1A2-inhibitor:   0.52 CYP1A2-substrate:   0.982
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.063
CYP2C9-inhibitor:   0.918 CYP2C9-substrate:   0.997
CYP2D6-inhibitor:   0.931 CYP2D6-substrate:   0.682
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.937
CYP2B6-substrate:   0.003 CYP2C8-inhibitor:   1.0
HLM stability:   0.987
?
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):  4.579 Half-life (T1/2):  0.902

ADMET: Toxicity

hERG Blockers:  0.208 hERG Blockers (10um):  0.556
Human Hepatotoxicity (H-HT):  0.518 Drug-induced Liver Injury (DILI):  0.825
AMES Toxicity:  0.763 Rat Oral Acute Toxicity:  0.732
Maximum Recommended Daily Dose:  0.869 Skin Sensitization:  0.288
Carcinogencity:  0.835 Eye Corrosion:  0.004
Eye Irritation:  0.952 Respiratory Toxicity:  0.907
Drug-induced Neurotoxicity:  0.288 Ototoxicity:  0.278
Hematotoxicity:  0.115 Drug-induced Nephrotoxicity:  0.242
Genotoxicity:  0.961 RPMI-8226 Immunitoxicity:  0.084
A549 Cytotoxicity:  0.213 Hek293 Cytotoxicity:  0.615
BCF:   1.575
?
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:   4.411
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.565
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.105
?
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
NPO29113 Erythrina vogelii Species Fabaceae Eukaryota root bark n.a. n.a. PMID[11908991]
NPO13906 Ficus mucuso Species Moraceae Eukaryota n.a. fruit n.a. PMID[21619045]
NPO13906 Ficus mucuso Species Moraceae Eukaryota figs Tongolo-Yaound, in the Central Region of Cameroon 2008-JUN PMID[21619045]
NPO13906 Ficus mucuso Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29113 Erythrina vogelii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29113 Erythrina vogelii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29113 Erythrina vogelii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13906 Ficus mucuso Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29113 Erythrina vogelii 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
NPT1333 Individual protein Enoyl-acyl-carrier protein reductase Plasmodium falciparum Inhibition = 24.1 % PMID[21619045]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Inhibition = 75.0 % PMID[9213587]
NPT2 Others Unspecified n.a. IC50 = 13130.0 nM PMID[22522694]

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 NPC474052 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
0.803 Intermediate Similarity NPC107838
0.7246 Intermediate Similarity NPC74178
0.7 Intermediate Similarity NPC231763
0.6528 Remote Similarity NPC303197
0.6234 Remote Similarity NPC303174
0.6176 Remote Similarity NPC254702
0.6154 Remote Similarity NPC78341
0.6129 Remote Similarity NPC39426
0.6119 Remote Similarity NPC200316
0.6061 Remote Similarity NPC294409
0.6061 Remote Similarity NPC490701
0.6 Remote Similarity NPC104406
0.5873 Remote Similarity NPC608554
0.5857 Remote Similarity NPC104728
0.5833 Remote Similarity NPC97716
0.5692 Remote Similarity NPC38065
0.5679 Remote Similarity NPC302762
0.5676 Remote Similarity NPC233918
0.5676 Remote Similarity NPC268059
0.5658 Remote Similarity NPC482075
0.5658 Remote Similarity NPC134796
0.5616 Remote Similarity NPC24673
0.56 Remote Similarity NPC479305
0.5571 Remote Similarity NPC194653
0.5571 Remote Similarity NPC481044
0.5507 Remote Similarity NPC239363
0.5469 Remote Similarity NPC193792
0.5465 Remote Similarity NPC121647
0.5429 Remote Similarity NPC309154
0.5405 Remote Similarity NPC213659
0.5405 Remote Similarity NPC326109
0.5385 Remote Similarity NPC52889
0.5385 Remote Similarity NPC108859
0.5385 Remote Similarity NPC609101
0.5286 Remote Similarity NPC19980
0.5278 Remote Similarity NPC483637
0.5263 Remote Similarity NPC475705
0.5256 Remote Similarity NPC84124
0.525 Remote Similarity NPC484043
0.5195 Remote Similarity NPC128774
0.5185 Remote Similarity NPC233502
0.5181 Remote Similarity NPC278968
0.5139 Remote Similarity NPC279668
0.5139 Remote Similarity NPC278323
0.5128 Remote Similarity NPC266572
0.5125 Remote Similarity NPC184755
0.5125 Remote Similarity NPC474960
0.5068 Remote Similarity NPC142876
0.5068 Remote Similarity NPC476055
0.5068 Remote Similarity NPC264550
0.5067 Remote Similarity NPC238279
0.5067 Remote Similarity NPC600644
0.5067 Remote Similarity NPC608523
0.5063 Remote Similarity NPC184547
0.5063 Remote Similarity NPC15435

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC474052 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
0.6129 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