Natural Product: NPC579400

Natural Product IDNPC579400
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5,7-dihydroxy-6-[(2~{S})-2-hydroxy-3-methyl-but-3-enyl]-3-(4-hydroxyphenyl)chromen-4-one
IUPAC Name 5,7-dihydroxy-6-[(2~{S})-2-hydroxy-3-methyl-but-3-enyl]-3-(4-hydroxyphenyl)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 GGHDLVXWIPWSLS-HNNXBMFYSA-N
Standard InCHI InChI=1S/C20H18O6/c1-10(2)15(22)7-13-16(23)8-17-18(19(13)24)20(25)14(9-26-17)11-3-5-12(21)6-4-11/h3-6,8-9,15,21-24H,1,7H2,2H3/t15-/m0/s1
SMILES C=C(C)[C@@H](O)CC1=C(O)C=C2OC=C(C3=CC=C(O)C=C3)C(=O)C2=C1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   354.11 Volume:   357.82
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Van der Waals volume.
Dense:   0.99 LogP:   1.84
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.073
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.56
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   111.13
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.536 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.267 Fsp3:   0.15
MCE-18:   40.0
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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:   0.625 Fluc inhibitor:   0.487
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.925
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.419
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.206 Promiscuous compounds:   0.242

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.061 MDCK Permeability:   -4.752
Pgp-inhibitor:   0.006 Pgp-substrate:   0.102
PAMPA:   0.952
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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%):   0.067 30% Bioavailability (F30%):   0.307
50% Bioavailability (F50%):   0.972

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.586
Plasma Protein Binding (PPB):   96.426% Volume Distribution (VD):   0.125
Fu: 3.739%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.451
OATP1B3 inhibitor:   0.234 BCRP inhibitor:   0.485
BSEP inhibitor:   0.935

ADMET: Metabolism

CYP1A2-inhibitor:   0.882 CYP1A2-substrate:   0.583
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.059
CYP2C9-inhibitor:   0.233 CYP2C9-substrate:   0.39
CYP2D6-inhibitor:   0.996 CYP2D6-substrate:   0.616
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.785
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.971
HLM stability:   0.118
?
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):  8.88 Half-life (T1/2):  1.339

ADMET: Toxicity

hERG Blockers:  0.09 hERG Blockers (10um):  0.478
Human Hepatotoxicity (H-HT):  0.51 Drug-induced Liver Injury (DILI):  0.191
AMES Toxicity:  0.36 Rat Oral Acute Toxicity:  0.4
Maximum Recommended Daily Dose:  0.906 Skin Sensitization:  0.654
Carcinogencity:  0.459 Eye Corrosion:  0.034
Eye Irritation:  0.988 Respiratory Toxicity:  0.565
Drug-induced Neurotoxicity:  0.119 Ototoxicity:  0.358
Hematotoxicity:  0.075 Drug-induced Nephrotoxicity:  0.083
Genotoxicity:  0.879 RPMI-8226 Immunitoxicity:  0.108
A549 Cytotoxicity:  0.088 Hek293 Cytotoxicity:  0.502
BCF:   1.084
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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:   3.763
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.765
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.355
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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
NPO19934 Genista ephedroides Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1021/np980112s]
NPO14905 Erythrina variegata Species Fabaceae Eukaryota n.a. root n.a. PMID[10869220]
NPO791 Laburnum anagyroides Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[23022271]
NPO3871 Maclura pomifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19934 Genista ephedroides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29226 Ficus cordata Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO53446 Ficus chlamydocarpa Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14905 Erythrina variegata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO49037 Erythrina suberosa var. glabrescences Genus Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO791 Laburnum anagyroides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3871 Maclura pomifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14905 Erythrina variegata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO791 Laburnum anagyroides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO791 Laburnum anagyroides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3871 Maclura pomifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14905 Erythrina variegata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO791 Laburnum anagyroides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14905 Erythrina variegata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19934 Genista ephedroides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29226 Ficus cordata Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3871 Maclura pomifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14905 Erythrina variegata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO791 Laburnum anagyroides 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

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 NPC579400 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
0.8167 Intermediate Similarity NPC51070
0.7812 Intermediate Similarity NPC476178
0.7541 Intermediate Similarity NPC259166
0.6716 Remote Similarity NPC475705
0.6667 Remote Similarity NPC117836
0.6429 Remote Similarity NPC51887
0.6364 Remote Similarity NPC20472
0.6269 Remote Similarity NPC482730
0.6119 Remote Similarity NPC486096
0.6087 Remote Similarity NPC48624
0.5942 Remote Similarity NPC268204
0.5857 Remote Similarity NPC40942
0.5797 Remote Similarity NPC222298
0.5738 Remote Similarity NPC39426
0.5676 Remote Similarity NPC323626
0.5652 Remote Similarity NPC55832
0.5556 Remote Similarity NPC168085
0.5538 Remote Similarity NPC269451
0.5493 Remote Similarity NPC203077
0.5467 Remote Similarity NPC324233
0.5429 Remote Similarity NPC204985
0.5417 Remote Similarity NPC219917
0.5286 Remote Similarity NPC144118
0.5278 Remote Similarity NPC213659
0.5278 Remote Similarity NPC326109
0.5185 Remote Similarity NPC302762
0.5139 Remote Similarity NPC604003
0.5068 Remote Similarity NPC97716
0.5062 Remote Similarity NPC278968

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC579400 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
0.5738 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