Natural Product: NPC99854

Natural Product IDNPC99854
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5,7,4'-Trimethoxyflavanone
IUPAC Name 5,7-dimethoxy-2-(4-methoxyphenyl)-2,3-dihydrochromen-4-one
Synonyms 5,7,4'-Trimethoxyflavanone
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL483550
PubChem CID 5003667
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002592] 7-O-methylated flavonoids

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 MQFSCAHSIUPLSB-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H18O5/c1-20-12-6-4-11(5-7-12)15-10-14(19)18-16(22-3)8-13(21-2)9-17(18)23-15/h4-9,15H,10H2,1-3H3
SMILES COc1ccc(cc1)C1CC(=O)c2c(O1)cc(cc2OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   314.12 Volume:   319.711
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Van der Waals volume.
Dense:   0.983 LogP:   2.956
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.153
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.543
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   53.99
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Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.865 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.58 Fsp3:   0.278
MCE-18:   53.957
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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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.282 Fluc inhibitor:   0.396
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.293
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.32
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.34 Promiscuous compounds:   0.373

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.643 MDCK Permeability:   -4.593
Pgp-inhibitor:   0.999 Pgp-substrate:   0.002
PAMPA:   0.003
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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):   0.253
20% Bioavailability (F20%):   0.002 30% Bioavailability (F30%):   0.101
50% Bioavailability (F50%):   0.743

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.181
Plasma Protein Binding (PPB):   88.781% Volume Distribution (VD):   -0.059
Fu: 9.297%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.992
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.992
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.996
CYP2C19-inhibitor:   0.997 CYP2C19-substrate:   0.934
CYP2C9-inhibitor:   0.995 CYP2C9-substrate:   0.041
CYP2D6-inhibitor:   0.986 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.141 CYP2C8-inhibitor:   0.146
HLM stability:   0.939
?
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):  6.36 Half-life (T1/2):  0.83

ADMET: Toxicity

hERG Blockers:  0.273 hERG Blockers (10um):  0.572
Human Hepatotoxicity (H-HT):  0.665 Drug-induced Liver Injury (DILI):  0.775
AMES Toxicity:  0.738 Rat Oral Acute Toxicity:  0.444
Maximum Recommended Daily Dose:  0.49 Skin Sensitization:  0.317
Carcinogencity:  0.85 Eye Corrosion:  0.032
Eye Irritation:  0.933 Respiratory Toxicity:  0.669
Drug-induced Neurotoxicity:  0.797 Ototoxicity:  0.384
Hematotoxicity:  0.582 Drug-induced Nephrotoxicity:  0.703
Genotoxicity:  0.38 RPMI-8226 Immunitoxicity:  0.118
A549 Cytotoxicity:  0.156 Hek293 Cytotoxicity:  0.437
BCF:   1.595
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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:   3.919
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.531
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.695
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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
NPO583 Goniothalamus gardneri Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO583 Goniothalamus gardneri Species Annonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO583 Goniothalamus gardneri Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO583 Goniothalamus gardneri Species Annonaceae 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
NPT71 Cell line HEK293 Homo sapiens FC = 0.7 n.a. PMID[19307119]
NPT91 Cell line KB Homo sapiens IC50 = 78800.0 nM PMID[20362442]
NPT639 Cell line NCI-H187 Homo sapiens IC50 = 25100.0 nM PMID[20362442]

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 NPC99854 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 NPC135616
0.6889 Remote Similarity NPC188243
0.6889 Remote Similarity NPC110228
0.6809 Remote Similarity NPC156057
0.6531 Remote Similarity NPC599987
0.6444 Remote Similarity NPC485642
0.6444 Remote Similarity NPC611561
0.6383 Remote Similarity NPC6407
0.6383 Remote Similarity NPC545184
0.6279 Remote Similarity NPC228184
0.6042 Remote Similarity NPC611253
0.5833 Remote Similarity NPC22467
0.5778 Remote Similarity NPC172253
0.5625 Remote Similarity NPC265871
0.5625 Remote Similarity NPC205093
0.56 Remote Similarity NPC150648
0.551 Remote Similarity NPC225153
0.551 Remote Similarity NPC479876
0.549 Remote Similarity NPC274784
0.549 Remote Similarity NPC20709
0.5294 Remote Similarity NPC162869
0.5283 Remote Similarity NPC469758
0.5192 Remote Similarity NPC329203
0.5192 Remote Similarity NPC222342
0.5091 Remote Similarity NPC259685

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC99854 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