Natural Product: NPC301123

Natural Product IDNPC301123
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Gnaphaliin B
IUPAC Name 3,5-dihydroxy-7,8-dimethoxy-2-phenylchromen-4-one
Synonyms Gnaphaliin B
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL549907
PubChem CID 5491798
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001615] Flavones
          • [CHEMONTID:0001136] Flavonols

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 CILMBWBPHLLNEH-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O6/c1-21-11-8-10(18)12-13(19)14(20)15(9-6-4-3-5-7-9)23-17(12)16(11)22-2/h3-8,18,20H,1-2H3
SMILES COc1cc(c2c(=O)c(c(c3ccccc3)oc2c1OC)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   314.08 Volume:   308.569
?
Van der Waals volume.
Dense:   1.018 LogP:   2.704
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.305
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.47
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   89.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.772 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.297 Fsp3:   0.118
MCE-18:   18.0
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.301 Fluc inhibitor:   0.51
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.688
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.53
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.328 Promiscuous compounds:   0.708

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.094 MDCK Permeability:   -4.751
Pgp-inhibitor:   0.965 Pgp-substrate:   0.021
PAMPA:   0.134
?
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):   0.015
20% Bioavailability (F20%):   0.017 30% Bioavailability (F30%):   0.346
50% Bioavailability (F50%):   0.734

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.123 MRP1:   0.913
Plasma Protein Binding (PPB):   98.439% Volume Distribution (VD):   -0.521
Fu: 0.859%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.917
OATP1B3 inhibitor:   0.993 BCRP inhibitor:   0.939
BSEP inhibitor:   0.986

ADMET: Metabolism

CYP1A2-inhibitor:   0.635 CYP1A2-substrate:   0.655
CYP2C19-inhibitor:   0.304 CYP2C19-substrate:   0.909
CYP2C9-inhibitor:   0.991 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.982 CYP2D6-substrate:   0.054
CYP3A4-inhibitor:   0.672 CYP3A4-substrate:   0.32
CYP2B6-substrate:   0.038 CYP2C8-inhibitor:   0.298
HLM stability:   0.767
?
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):  5.754 Half-life (T1/2):  1.424

ADMET: Toxicity

hERG Blockers:  0.09 hERG Blockers (10um):  0.484
Human Hepatotoxicity (H-HT):  0.478 Drug-induced Liver Injury (DILI):  0.873
AMES Toxicity:  0.484 Rat Oral Acute Toxicity:  0.493
Maximum Recommended Daily Dose:  0.458 Skin Sensitization:  0.516
Carcinogencity:  0.683 Eye Corrosion:  0.221
Eye Irritation:  0.966 Respiratory Toxicity:  0.702
Drug-induced Neurotoxicity:  0.157 Ototoxicity:  0.152
Hematotoxicity:  0.276 Drug-induced Nephrotoxicity:  0.137
Genotoxicity:  0.515 RPMI-8226 Immunitoxicity:  0.072
A549 Cytotoxicity:  0.217 Hek293 Cytotoxicity:  0.308
BCF:   1.094
?
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:   3.958
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.781
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.347
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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
NPO12600 Trametes cinnabarina Species Coriolaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23127 Mussaenda shikokiana Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23659 Rostellularia procumbens n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO23659 Rostellularia procumbens n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO23659 Rostellularia procumbens n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO23659 Rostellularia procumbens n.a. n.a. n.a. n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12600 Trametes cinnabarina Species Coriolaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23285 Neocallitropsis pancheri Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24948 Stevia lemmoni Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24695 Campanula kolenatiana Species Campanulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8973 Orthosiphon grandiflorus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22332 Primula imperialis Species Primulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23659 Rostellularia procumbens n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO19577 Streptomyces albosporeus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO23127 Mussaenda shikokiana Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20174 Limonium aureum Species Plumbaginaceae 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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. EC50 = 63.05 ug.mL-1 PMID[19505084]

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 NPC301123 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
0.8235 Intermediate Similarity NPC86485
0.7759 Intermediate Similarity NPC606048
0.7037 Intermediate Similarity NPC608038
0.6852 Remote Similarity NPC189960
0.6852 Remote Similarity NPC306821
0.6852 Remote Similarity NPC152042
0.678 Remote Similarity NPC259411
0.678 Remote Similarity NPC480464
0.6071 Remote Similarity NPC26227
0.5862 Remote Similarity NPC201451
0.5667 Remote Similarity NPC178854
0.5593 Remote Similarity NPC32557
0.5593 Remote Similarity NPC143799
0.5593 Remote Similarity NPC605144
0.5574 Remote Similarity NPC224137
0.55 Remote Similarity NPC607913
0.541 Remote Similarity NPC166753
0.5357 Remote Similarity NPC187432
0.5357 Remote Similarity NPC128216
0.5333 Remote Similarity NPC87125
0.5333 Remote Similarity NPC605755
0.5323 Remote Similarity NPC189179
0.5323 Remote Similarity NPC474520
0.5323 Remote Similarity NPC603112
0.5323 Remote Similarity NPC610401
0.5246 Remote Similarity NPC32420
0.5246 Remote Similarity NPC480465
0.5238 Remote Similarity NPC152166
0.5231 Remote Similarity NPC603082
0.5195 Remote Similarity NPC295082
0.5167 Remote Similarity NPC103904
0.5167 Remote Similarity NPC127447
0.5161 Remote Similarity NPC200740
0.5082 Remote Similarity NPC241838

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC301123 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