Natural Product: NPC85162

Natural Product IDNPC85162
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Exiguaflavone A
IUPAC Name (2S)-2-(2,6-dihydroxyphenyl)-5,7-dihydroxy-8-[(2R)-5-methyl-2-prop-1-en-2-ylhex-4-enyl]-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL464368
PubChem CID 15735861
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003642] 8-prenylated flavans
            • [CHEMONTID:0003508] 8-prenylated flavanones

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 FPUREMWTZVLZBZ-QRQCRPRQSA-N
Standard InCHI InChI=1S/C25H28O6/c1-13(2)8-9-15(14(3)4)10-16-19(28)11-20(29)24-21(30)12-22(31-25(16)24)23-17(26)6-5-7-18(23)27/h5-8,11,15,22,26-29H,3,9-10,12H2,1-2,4H3/t15-,22+/m1/s1
SMILES CC(=CC[C@@H](C(=C)C)Cc1c(O)cc(c2c1O[C@@H](CC2=O)c1c(O)cccc1O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   424.19 Volume:   444.3
?
Van der Waals volume.
Dense:   0.955 LogP:   4.401
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.643
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.865
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   20.0
TPSA:   107.22
?
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:   0.468 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.005 Fsp3:   0.32
MCE-18:   68.667
?
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:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.937 Fluc inhibitor:   0.531
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.357
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.476
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.516 Promiscuous compounds:   0.073

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.944 MDCK Permeability:   -4.696
Pgp-inhibitor:   0.348 Pgp-substrate:   0.275
PAMPA:   0.08
?
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):   0.0
20% Bioavailability (F20%):   0.007 30% Bioavailability (F30%):   0.046
50% Bioavailability (F50%):   0.625

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.152 MRP1:   0.948
Plasma Protein Binding (PPB):   95.103% Volume Distribution (VD):   0.684
Fu: 5.534%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.563
OATP1B3 inhibitor:   0.385 BCRP inhibitor:   0.486
BSEP inhibitor:   0.858

ADMET: Metabolism

CYP1A2-inhibitor:   0.351 CYP1A2-substrate:   0.424
CYP2C19-inhibitor:   0.028 CYP2C19-substrate:   0.95
CYP2C9-inhibitor:   0.996 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.742 CYP2D6-substrate:   0.112
CYP3A4-inhibitor:   0.971 CYP3A4-substrate:   0.998
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.264
HLM stability:   0.499
?
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):  2.267 Half-life (T1/2):  1.684

ADMET: Toxicity

hERG Blockers:  0.068 hERG Blockers (10um):  0.446
Human Hepatotoxicity (H-HT):  0.847 Drug-induced Liver Injury (DILI):  0.736
AMES Toxicity:  0.608 Rat Oral Acute Toxicity:  0.739
Maximum Recommended Daily Dose:  0.934 Skin Sensitization:  0.99
Carcinogencity:  0.089 Eye Corrosion:  0.001
Eye Irritation:  0.937 Respiratory Toxicity:  0.962
Drug-induced Neurotoxicity:  0.743 Ototoxicity:  0.631
Hematotoxicity:  0.052 Drug-induced Nephrotoxicity:  0.569
Genotoxicity:  0.978 RPMI-8226 Immunitoxicity:  0.213
A549 Cytotoxicity:  0.938 Hek293 Cytotoxicity:  0.442
BCF:   1.884
?
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:   4.693
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.54
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.78
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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
NPO24630 Sophora exigua Species Fabaceae Eukaryota n.a. root n.a. DOI[10.1016/0031-9422(92)80056-K]
NPO24630 Sophora exigua Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[10839220]
NPO74 Artemisia indica Species Asteraceae Eukaryota n.a. stem n.a. PMID[9748386]
NPO24630 Sophora exigua Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO74 Artemisia indica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24630 Sophora exigua 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
NPT485 Organism Plasmodium falciparum (isolate K1 / Thailand) Plasmodium falciparum K1 EC50 = 10800.0 nM PMID[9748386]

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 NPC85162 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
0.8226 Intermediate Similarity NPC81697
0.8226 Intermediate Similarity NPC485615
0.7656 Intermediate Similarity NPC278249
0.7656 Intermediate Similarity NPC223812
0.7273 Intermediate Similarity NPC125894
0.7 Intermediate Similarity NPC107177
0.7 Intermediate Similarity NPC485612
0.6286 Remote Similarity NPC131568
0.5915 Remote Similarity NPC473015
0.589 Remote Similarity NPC485618
0.589 Remote Similarity NPC485617
0.5833 Remote Similarity NPC131579
0.5833 Remote Similarity NPC485613
0.5821 Remote Similarity NPC306829
0.5676 Remote Similarity NPC216035
0.56 Remote Similarity NPC77794
0.56 Remote Similarity NPC225660
0.5467 Remote Similarity NPC485619
0.5441 Remote Similarity NPC76372
0.5441 Remote Similarity NPC37496
0.5405 Remote Similarity NPC300988
0.5385 Remote Similarity NPC285630
0.5362 Remote Similarity NPC324436
0.5362 Remote Similarity NPC78
0.5362 Remote Similarity NPC107572
0.5362 Remote Similarity NPC32739
0.5333 Remote Similarity NPC473014
0.5325 Remote Similarity NPC473013
0.5325 Remote Similarity NPC235217
0.5325 Remote Similarity NPC485611
0.5211 Remote Similarity NPC66515
0.5205 Remote Similarity NPC10990
0.5205 Remote Similarity NPC485620
0.507 Remote Similarity NPC148757
0.5068 Remote Similarity NPC182852

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC85162 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