Natural Product: NPC475267

Natural Product IDNPC475267
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5,4'-Dihydroxy-6,7-Dimethoxyflavanone
IUPAC Name 5-hydroxy-2-(4-hydroxyphenyl)-6,7-dimethoxy-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL502359
PubChem CID 14078484
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 DEOJMRBCCZJDEC-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H16O6/c1-21-14-8-13-15(16(20)17(14)22-2)11(19)7-12(23-13)9-3-5-10(18)6-4-9/h3-6,8,12,18,20H,7H2,1-2H3
SMILES COC1=C(C(=C2C(=O)CC(OC2=C1)C3=CC=C(C=C3)O)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.09 Volume:   311.205
?
Van der Waals volume.
Dense:   1.016 LogP:   2.461
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.729
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.173
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   85.22
?
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:   0.905 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.848 Fsp3:   0.235
MCE-18:   57.429
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.374 Fluc inhibitor:   0.413
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.159
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.301
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.314 Promiscuous compounds:   0.037

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.003 MDCK Permeability:   -4.786
Pgp-inhibitor:   0.987 Pgp-substrate:   0.146
PAMPA:   0.184
?
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):   0.004
20% Bioavailability (F20%):   0.003 30% Bioavailability (F30%):   0.264
50% Bioavailability (F50%):   0.984

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.913
Plasma Protein Binding (PPB):   96.104% Volume Distribution (VD):   -0.473
Fu: 3.666%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.968
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.996
BSEP inhibitor:   0.977

ADMET: Metabolism

CYP1A2-inhibitor:   0.6 CYP1A2-substrate:   0.474
CYP2C19-inhibitor:   0.278 CYP2C19-substrate:   0.83
CYP2C9-inhibitor:   0.337 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.424 CYP2D6-substrate:   0.916
CYP3A4-inhibitor:   0.026 CYP3A4-substrate:   0.165
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.258
HLM stability:   0.875
?
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):  5.686 Half-life (T1/2):  1.288

ADMET: Toxicity

hERG Blockers:  0.154 hERG Blockers (10um):  0.576
Human Hepatotoxicity (H-HT):  0.676 Drug-induced Liver Injury (DILI):  0.432
AMES Toxicity:  0.571 Rat Oral Acute Toxicity:  0.53
Maximum Recommended Daily Dose:  0.553 Skin Sensitization:  0.715
Carcinogencity:  0.712 Eye Corrosion:  0.023
Eye Irritation:  0.968 Respiratory Toxicity:  0.597
Drug-induced Neurotoxicity:  0.546 Ototoxicity:  0.366
Hematotoxicity:  0.294 Drug-induced Nephrotoxicity:  0.488
Genotoxicity:  0.59 RPMI-8226 Immunitoxicity:  0.107
A549 Cytotoxicity:  0.333 Hek293 Cytotoxicity:  0.667
BCF:   1.057
?
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:   3.642
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.772
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.095
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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
NPO11318 Eriodictyon californicum Species Namaceae Eukaryota n.a. n.a. n.a. PMID[1593282]
NPO11318 Eriodictyon californicum Species Namaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11318 Eriodictyon californicum Species Namaceae 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
NPT2 Others Unspecified n.a. Inhibition = -36.0 % PMID[10924160]

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 NPC475267 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
0.7451 Intermediate Similarity NPC48208
0.7451 Intermediate Similarity NPC601395
0.7059 Intermediate Similarity NPC329203
0.7059 Intermediate Similarity NPC222342
0.6923 Remote Similarity NPC606248
0.6154 Remote Similarity NPC225153
0.6154 Remote Similarity NPC479876
0.6102 Remote Similarity NPC69674
0.6038 Remote Similarity NPC32441
0.6038 Remote Similarity NPC79943
0.6 Remote Similarity NPC470131
0.6 Remote Similarity NPC470132
0.6 Remote Similarity NPC210084
0.5902 Remote Similarity NPC486094
0.5818 Remote Similarity NPC300668
0.5818 Remote Similarity NPC324386
0.5769 Remote Similarity NPC329225
0.5769 Remote Similarity NPC147686
0.5741 Remote Similarity NPC6407
0.5741 Remote Similarity NPC545184
0.5714 Remote Similarity NPC485881
0.5714 Remote Similarity NPC469764
0.5636 Remote Similarity NPC150648
0.5636 Remote Similarity NPC162869
0.5536 Remote Similarity NPC255106
0.5536 Remote Similarity NPC480993
0.5536 Remote Similarity NPC235165
0.55 Remote Similarity NPC169591
0.55 Remote Similarity NPC298223
0.55 Remote Similarity NPC604412
0.5455 Remote Similarity NPC482487
0.5455 Remote Similarity NPC603284
0.5424 Remote Similarity NPC474836
0.5357 Remote Similarity NPC167624
0.5357 Remote Similarity NPC166482
0.5345 Remote Similarity NPC18727
0.5345 Remote Similarity NPC310135
0.5345 Remote Similarity NPC474208
0.5323 Remote Similarity NPC470178
0.5263 Remote Similarity NPC274784
0.5263 Remote Similarity NPC73028
0.5263 Remote Similarity NPC20709
0.5238 Remote Similarity NPC470133
0.5238 Remote Similarity NPC220998
0.5238 Remote Similarity NPC477840
0.5156 Remote Similarity NPC134171
0.5091 Remote Similarity NPC265871
0.5091 Remote Similarity NPC205093
0.5088 Remote Similarity NPC37392
0.5082 Remote Similarity NPC236637

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC475267 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
0.6038 Remote Similarity NPD1552 Clinical (unspecified phase)
0.5769 Remote Similarity NPD1549 Phase 2

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