Natural Product: NPC196034

Natural Product IDNPC196034
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
IUPAC Name 2-(4-bromophenyl)chromen-4-one
Synonyms 4'-Bromoflavone; 4-Bromoflavone
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL294099
PubChem CID 1686
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001615] Flavones

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 URZUAHXELZUWFE-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H9BrO2/c16-11-7-5-10(6-8-11)15-9-13(17)12-3-1-2-4-14(12)18-15/h1-9H
SMILES Brc1ccc(cc1)c1cc(=O)c2c(o1)cccc2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   299.98 Volume:   258.099
?
Van der Waals volume.
Dense:   1.162 LogP:   4.17
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.162
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.099
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   18.0
TPSA:   30.21
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.673 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.805 Fsp3:   0.0
MCE-18:   15.0
?
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:   0.955 Fluc inhibitor:   0.997
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.847
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.943
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.964 Promiscuous compounds:   0.997

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.838 MDCK Permeability:   -4.643
Pgp-inhibitor:   0.987 Pgp-substrate:   0.018
PAMPA:   0.17
?
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%):   0.027 30% Bioavailability (F30%):   0.101
50% Bioavailability (F50%):   0.3

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.961 MRP1:   0.876
Plasma Protein Binding (PPB):   98.593% Volume Distribution (VD):   -0.037
Fu: 0.789%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.975
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.683
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.141 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.233 CYP2C19-substrate:   0.631
CYP2C9-inhibitor:   0.972 CYP2C9-substrate:   0.987
CYP2D6-inhibitor:   0.7 CYP2D6-substrate:   0.937
CYP3A4-inhibitor:   0.041 CYP3A4-substrate:   0.996
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.473
?
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):  3.821 Half-life (T1/2):  0.888

ADMET: Toxicity

hERG Blockers:  0.191 hERG Blockers (10um):  0.564
Human Hepatotoxicity (H-HT):  0.433 Drug-induced Liver Injury (DILI):  0.935
AMES Toxicity:  0.344 Rat Oral Acute Toxicity:  0.543
Maximum Recommended Daily Dose:  0.833 Skin Sensitization:  0.607
Carcinogencity:  0.751 Eye Corrosion:  0.415
Eye Irritation:  0.985 Respiratory Toxicity:  0.547
Drug-induced Neurotoxicity:  0.37 Ototoxicity:  0.083
Hematotoxicity:  0.231 Drug-induced Nephrotoxicity:  0.154
Genotoxicity:  0.974 RPMI-8226 Immunitoxicity:  0.044
A549 Cytotoxicity:  0.146 Hek293 Cytotoxicity:  0.366
BCF:   2.316
?
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:   4.456
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.633
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.192
?
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
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.jarmap.2018.11.004]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. leaf n.a. PMID[11348221]
NPO33342 Bruguiera gymnorrhiza Species Rhizophoraceae Eukaryota stems Xiamen, China 2002-JUN PMID[15387677]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota fruit n.a. n.a. PMID[15844957]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota fruits n.a. n.a. PMID[16378361]
NPO33342 Bruguiera gymnorrhiza Species Rhizophoraceae Eukaryota n.a. n.a. n.a. PMID[16562850]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota fruits Tahiti n.a. PMID[17378609]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota Fruits n.a. n.a. PMID[17480098]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota roots n.a. n.a. PMID[18076142]
NPO33173 nocardiopsis Genus Nocardiopsaceae Bacteria n.a. n.a. n.a. PMID[20481500]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[24224843]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[27196335]
NPO13114 Pleiocarpa pycnantha Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[29664292]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota Fruits n.a. n.a. PMID[32083868]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[36014413]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13114 Pleiocarpa pycnantha Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO33173 nocardiopsis Genus Nocardiopsaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO33342 Bruguiera gymnorrhiza Species Rhizophoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4323 Morinda citrifolia Species Rubiaceae 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
NPT1651 Individual protein Nuclear factor erythroid 2-related factor 2 Mus musculus FC = 4.45 n.a. DOI[10.1039/C6MD00456C]
NPT1651 Individual protein Nuclear factor erythroid 2-related factor 2 Mus musculus FC = 1.49 n.a. DOI[10.1039/C6MD00456C]
NPT1651 Individual protein Nuclear factor erythroid 2-related factor 2 Mus musculus Ratio = 2.99 n.a. DOI[10.1039/C6MD00456C]
NPT1651 Individual protein Nuclear factor erythroid 2-related factor 2 Mus musculus CD = 0.79 uM DOI[10.1039/C6MD00456C]
NPT1651 Individual protein Nuclear factor erythroid 2-related factor 2 Mus musculus CD = 80.0 uM DOI[10.1039/C6MD00456C]
NPT1651 Individual protein Nuclear factor erythroid 2-related factor 2 Mus musculus Ratio = 101.3 n.a. DOI[10.1039/C6MD00456C]
NPT365 Individual protein NAD(P)H dehydrogenase [quinone] 1 Mus musculus CD = 0.013 uM PMID[23398362]
NPT365 Individual protein NAD(P)H dehydrogenase [quinone] 1 Mus musculus CD = 0.01 uM PMID[21334121]
NPT365 Individual protein NAD(P)H dehydrogenase [quinone] 1 Mus musculus CD = 20.0 nM PMID[16472241]
NPT365 Individual protein NAD(P)H dehydrogenase [quinone] 1 Mus musculus Ratio = 4.2 n.a. PMID[16472241]
NPT365 Individual protein NAD(P)H dehydrogenase [quinone] 1 Mus musculus Ratio = 2.17 n.a. PMID[16417306]
NPT365 Individual protein NAD(P)H dehydrogenase [quinone] 1 Mus musculus FC = 2.9 n.a. PubChem BioAssay data set
NPT365 Individual protein NAD(P)H dehydrogenase [quinone] 1 Mus musculus CD = 0.02 uM PMID[28812892]
NPT588 Individual protein Tankyrase-1 Homo sapiens IC50 = 316.23 nM PMID[19433554]
NPT588 Individual protein Tankyrase-1 Homo sapiens IC50 = 313.0 nM PMID[8254346]
NPT935 Individual protein Quinone reductase 1) Homo sapiens CD = 0.01 uM PMID[27196335]
NPT805 Protein complex GABA-A receptor; anion channel Rattus norvegicus Ki > 20000.0 nM PMID[21080703]
NPT440 Individual protein Quinone oxidoreductase Mus musculus Activity = 0.023 uM PMID[24369840]
NPT440 Individual protein Quinone oxidoreductase Mus musculus Activity > 250.0 uM PMID[24369840]
NPT440 Individual protein Quinone oxidoreductase Mus musculus CD = 19.2 uM PMID[29664292]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT384 Cell line TK-10 Homo sapiens Activity = 94.0 % PMID[4020828]
NPT83 Cell line MCF7 Homo sapiens Activity = 73.0 % PMID[12608862]
NPT139 Cell line HT-29 Homo sapiens Activity = 100.0 % PMID[7798956]
NPT65 Cell line HepG2 Homo sapiens EC50 = 30000.0 nM PMID[23398362]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 > 25000.0 nM PMID[18667308]
NPT28438 Unchecked Unchecked n.a. log(ratio) = 0.4 n.a. PMID[35576701]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 109.0 % PMID[25630222]
NPT29337 Protein family Cytochrome P450 Homo sapiens Inhibition < 15.0 % PMID[35576701]
NPT29337 Protein family Cytochrome P450 Homo sapiens Inhibition = 35.0 % PMID[35576701]
NPT2 Others Unspecified n.a. IC50 > 62500.0 nM PMID[24369840]
NPT2 Others Unspecified n.a. Ratio > 2700.0 n.a. PMID[24369840]
NPT2 Others Unspecified n.a. FC = 4.45 n.a. PMID[16643039]
NPT2 Others Unspecified n.a. FC = 1.49 n.a. PMID[25554367]
NPT2 Others Unspecified n.a. Ratio = 2.99 n.a. PMID[18597527]
NPT2 Others Unspecified n.a. CD = 0.79 uM PMID[15568791]
NPT2 Others Unspecified n.a. Ratio = 107.0 n.a. PMID[22940448]
NPT2 Others Unspecified n.a. Ratio = 100.0 n.a. PMID[11473417]
NPT2 Others Unspecified n.a. Ratio = 1.9 n.a. PMID[17498960]
NPT2 Others Unspecified n.a. CD = 80.0 uM PMID[16279766]
NPT2 Others Unspecified n.a. IC50 = 85000.0 nM PMID[1336040]
NPT2 Others Unspecified n.a. IC50 = 150000.0 nM PMID[7996553]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT29 Organism Rattus norvegicus Rattus norvegicus Activity = 30.0 % PMID[18989978]





 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 NPC196034 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
0.7442 Intermediate Similarity NPC32298
0.6667 Remote Similarity NPC22783
0.64 Remote Similarity NPC2771
0.5769 Remote Similarity NPC483772
0.5769 Remote Similarity NPC603094
0.5741 Remote Similarity NPC77955
0.5741 Remote Similarity NPC608264
0.5577 Remote Similarity NPC193805
0.5455 Remote Similarity NPC483774
0.5273 Remote Similarity NPC608669

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC196034 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