Natural Product: NPC157855

Natural Product IDNPC157855
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2'',2''-Dimethylchromene-[5'',6'':7,8]-Flavone
IUPAC Name 8,8-dimethyl-2-phenylpyrano[2,3-f]chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3401058
PubChem CID 11358607
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0003520] Pyranoflavonoids

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 RBKWJAHRWPDNPM-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H16O3/c1-20(2)11-10-15-17(23-20)9-8-14-16(21)12-18(22-19(14)15)13-6-4-3-5-7-13/h3-12H,1-2H3
SMILES CC1(C)C=Cc2c(ccc3c(=O)cc(c4ccccc4)oc23)O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   304.11 Volume:   322.893
?
Van der Waals volume.
Dense:   0.942 LogP:   4.639
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.881
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.424
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   23.0
TPSA:   39.44
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.657 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.542 Fsp3:   0.15
MCE-18:   45.913
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.93 Fluc inhibitor:   0.883
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.91
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.822
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.599 Promiscuous compounds:   0.247

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.661 MDCK Permeability:   -4.65
Pgp-inhibitor:   0.99 Pgp-substrate:   0.028
PAMPA:   0.241
?
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%):   0.198 30% Bioavailability (F30%):   0.676
50% Bioavailability (F50%):   0.923

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.893 MRP1:   0.857
Plasma Protein Binding (PPB):   98.734% Volume Distribution (VD):   0.225
Fu: 0.736%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.981
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.964
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.025 CYP1A2-substrate:   0.997
CYP2C19-inhibitor:   0.145 CYP2C19-substrate:   0.547
CYP2C9-inhibitor:   0.998 CYP2C9-substrate:   0.834
CYP2D6-inhibitor:   0.799 CYP2D6-substrate:   0.879
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.002 CYP2C8-inhibitor:   1.0
HLM stability:   0.909
?
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):  4.923 Half-life (T1/2):  0.831

ADMET: Toxicity

hERG Blockers:  0.132 hERG Blockers (10um):  0.458
Human Hepatotoxicity (H-HT):  0.504 Drug-induced Liver Injury (DILI):  0.91
AMES Toxicity:  0.698 Rat Oral Acute Toxicity:  0.581
Maximum Recommended Daily Dose:  0.693 Skin Sensitization:  0.487
Carcinogencity:  0.885 Eye Corrosion:  0.087
Eye Irritation:  0.936 Respiratory Toxicity:  0.779
Drug-induced Neurotoxicity:  0.26 Ototoxicity:  0.125
Hematotoxicity:  0.258 Drug-induced Nephrotoxicity:  0.165
Genotoxicity:  0.915 RPMI-8226 Immunitoxicity:  0.067
A549 Cytotoxicity:  0.083 Hek293 Cytotoxicity:  0.438
BCF:   1.802
?
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:   4.658
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.081
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.695
?
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
NPO19856 Millettia pulchra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[25630222]
NPO19856 Millettia pulchra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21535 Bursera leptophloeos Species Burseraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21131 Lepista nuda Species Tricholomataceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21131 Lepista nuda Species Tricholomataceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21131 Lepista nuda Species Tricholomataceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19856 Millettia pulchra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23181 Ursinia eckloniana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19409 Vespa crabro Species Vespidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21535 Bursera leptophloeos Species Burseraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21131 Lepista nuda Species Tricholomataceae 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
NPT365 Individual protein NAD(P)H dehydrogenase [quinone] 1 Mus musculus Ratio = 1.6 n.a. PMID[25630222]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 99.0 % PMID[25630222]

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 NPC157855 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
0.7049 Intermediate Similarity NPC602756
0.6935 Remote Similarity NPC17848
0.6935 Remote Similarity NPC472408
0.6935 Remote Similarity NPC259456
0.5735 Remote Similarity NPC293852
0.5634 Remote Similarity NPC486089
0.5429 Remote Similarity NPC170492
0.5417 Remote Similarity NPC486092
0.5417 Remote Similarity NPC19554
0.5417 Remote Similarity NPC302741
0.5417 Remote Similarity NPC43971
0.5417 Remote Similarity NPC486091
0.5417 Remote Similarity NPC74749
0.5342 Remote Similarity NPC486090
0.5294 Remote Similarity NPC607923
0.5217 Remote Similarity NPC600644
0.52 Remote Similarity NPC470625
0.52 Remote Similarity NPC606770
0.52 Remote Similarity NPC610193
0.5143 Remote Similarity NPC482696
0.5079 Remote Similarity NPC13007

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC157855 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