Natural Product: NPC201395

Natural Product IDNPC201395
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-Methyl-2-Phenylchromen-4-One
IUPAC Name 5,7-dihydroxy-6-methyl-2-phenylchromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL163960
PubChem CID 11536318
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 XRJWLVUOUWIPHW-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H12O4/c1-9-11(17)7-14-15(16(9)19)12(18)8-13(20-14)10-5-3-2-4-6-10/h2-8,17,19H,1H3
SMILES Oc1cc2oc(cc(=O)c2c(c1C)O)c1ccccc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   268.07 Volume:   273.692
?
Van der Waals volume.
Dense:   0.979 LogP:   3.556
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.186
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.778
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   18.0
TPSA:   70.67
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.711 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.227 Fsp3:   0.062
MCE-18:   17.0
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.648 Fluc inhibitor:   0.924
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.93
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.744
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.601 Promiscuous compounds:   0.409

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.818 MDCK Permeability:   -4.724
Pgp-inhibitor:   0.77 Pgp-substrate:   0.088
PAMPA:   0.415
?
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):   0.002
20% Bioavailability (F20%):   0.131 30% Bioavailability (F30%):   0.587
50% Bioavailability (F50%):   0.839

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.241 MRP1:   0.915
Plasma Protein Binding (PPB):   97.876% Volume Distribution (VD):   -0.168
Fu: 1.563%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.95
OATP1B3 inhibitor:   0.957 BCRP inhibitor:   0.621
BSEP inhibitor:   0.969

ADMET: Metabolism

CYP1A2-inhibitor:   0.766 CYP1A2-substrate:   0.578
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.01
CYP2C9-inhibitor:   0.978 CYP2C9-substrate:   0.082
CYP2D6-inhibitor:   0.998 CYP2D6-substrate:   0.996
CYP3A4-inhibitor:   0.03 CYP3A4-substrate:   0.312
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.49
?
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):  5.935 Half-life (T1/2):  0.809

ADMET: Toxicity

hERG Blockers:  0.066 hERG Blockers (10um):  0.485
Human Hepatotoxicity (H-HT):  0.494 Drug-induced Liver Injury (DILI):  0.773
AMES Toxicity:  0.617 Rat Oral Acute Toxicity:  0.573
Maximum Recommended Daily Dose:  0.758 Skin Sensitization:  0.739
Carcinogencity:  0.686 Eye Corrosion:  0.31
Eye Irritation:  0.995 Respiratory Toxicity:  0.93
Drug-induced Neurotoxicity:  0.079 Ototoxicity:  0.097
Hematotoxicity:  0.147 Drug-induced Nephrotoxicity:  0.057
Genotoxicity:  0.962 RPMI-8226 Immunitoxicity:  0.071
A549 Cytotoxicity:  0.321 Hek293 Cytotoxicity:  0.647
BCF:   1.305
?
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:   4.087
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.124
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.687
?
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
NPO809 Leitneria floridana Species Simaroubaceae Eukaryota n.a. aerial part n.a. PMID[11141127]
NPO27517 Crinum latifolium Species Amaryllidaceae Eukaryota n.a. leaf n.a. PMID[15595606]
NPO5635 Bauhinia purpurea Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[16562827]
NPO5635 Bauhinia purpurea Species Fabaceae Eukaryota roots Phitsanulok Province, Thailand 2004-MAY PMID[17480099]
NPO5635 Bauhinia purpurea Species Fabaceae Eukaryota n.a. root n.a. PMID[17480099]
NPO4382 Elmerrillia papuana n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO27517 Crinum latifolium Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3357 Alnus cordata Species Betulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4628 Aloe deltoideodonta Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5635 Bauhinia purpurea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2455 Thermopsis mollis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1490 Goldfussia yunnanensis n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO8807 Laurentia longiflora n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO809 Leitneria floridana Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9608 Lepraria citrina Species Stereocaulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8977 Notholaena aschenborniana Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9881 Petrosia hebes Species Petrosiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6828 Purpura aperta Species Muricidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25475 Syphonota geographica Species Aplysiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27517 Crinum latifolium Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27517 Crinum latifolium Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27517 Crinum latifolium Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5635 Bauhinia purpurea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25475 Syphonota geographica Species Aplysiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4382 Elmerrillia papuana n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO8807 Laurentia longiflora n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO809 Leitneria floridana Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9608 Lepraria citrina Species Stereocaulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6828 Purpura aperta Species Muricidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2455 Thermopsis mollis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3357 Alnus cordata Species Betulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8977 Notholaena aschenborniana Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4628 Aloe deltoideodonta Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9881 Petrosia hebes Species Petrosiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1490 Goldfussia yunnanensis n.a. n.a. n.a. 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
NPT668 Individual protein P-glycoprotein 1 Homo sapiens Kd = 3090.3 nM PMID[21723648]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT111 Cell line K562 Homo sapiens Relative daunomycin accumulation = 0.2 n.a. PMID[11262086]
NPT139 Cell line HT-29 Homo sapiens Activity = 104.0 n.a. PMID[15828817]
NPT139 Cell line HT-29 Homo sapiens Activity = 100.0 n.a. PMID[15828817]

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 NPC201395 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
0.76 Intermediate Similarity NPC482122
0.6481 Remote Similarity NPC18260
0.6333 Remote Similarity NPC14871
0.6275 Remote Similarity NPC239312
0.6275 Remote Similarity NPC78540
0.6182 Remote Similarity NPC606332
0.6111 Remote Similarity NPC293183
0.5769 Remote Similarity NPC197425
0.5667 Remote Similarity NPC284220
0.5614 Remote Similarity NPC53181
0.5536 Remote Similarity NPC473042
0.5484 Remote Similarity NPC486096
0.5439 Remote Similarity NPC275722
0.5439 Remote Similarity NPC127447
0.5439 Remote Similarity NPC239128
0.5397 Remote Similarity NPC603717
0.537 Remote Similarity NPC57601
0.5323 Remote Similarity NPC3825
0.5312 Remote Similarity NPC189706
0.5294 Remote Similarity NPC108113
0.5254 Remote Similarity NPC78913
0.5172 Remote Similarity NPC194281
0.5172 Remote Similarity NPC609062
0.5091 Remote Similarity NPC50898
0.5091 Remote Similarity NPC259713
0.5085 Remote Similarity NPC602791
0.5082 Remote Similarity NPC606140
0.5082 Remote Similarity NPC608539
0.5077 Remote Similarity NPC59210

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC201395 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