Natural Product: NPC498322

Natural Product IDNPC498322
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2r)-5,7,4'-trihydroxy-8-methylflavanone
IUPAC Name (2~{R})-5,7-dihydroxy-2-(4-hydroxyphenyl)-8-methyl-chroman-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0001632] Flavanones

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 GMVYLXBMPRDZDR-CQSZACIVSA-N
Standard InCHI InChI=1S/C16H14O5/c1-8-11(18)6-12(19)15-13(20)7-14(21-16(8)15)9-2-4-10(17)5-3-9/h2-6,14,17-19H,7H2,1H3/t14-/m1/s1
SMILES CC1=C(O)C=C(O)C2=C1O[C@@H](C1=CC=C(O)C=C1)CC2=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   286.08 Volume:   285.119
?
Van der Waals volume.
Dense:   1.003 LogP:   2.912
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.787
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.542
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   18.0
TPSA:   86.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.75 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.001 Fsp3:   0.188
MCE-18:   57.789
?
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:   0.701 Fluc inhibitor:   0.827
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.41
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.229
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.375 Promiscuous compounds:   0.066

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.104 MDCK Permeability:   -4.777
Pgp-inhibitor:   0.975 Pgp-substrate:   0.257
PAMPA:   0.33
?
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):   0.0
20% Bioavailability (F20%):   0.001 30% Bioavailability (F30%):   0.757
50% Bioavailability (F50%):   0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.984
Plasma Protein Binding (PPB):   96.582% Volume Distribution (VD):   0.145
Fu: 3.853%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.984
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.998
BSEP inhibitor:   0.915

ADMET: Metabolism

CYP1A2-inhibitor:   0.862 CYP1A2-substrate:   0.558
CYP2C19-inhibitor:   0.04 CYP2C19-substrate:   0.955
CYP2C9-inhibitor:   0.414 CYP2C9-substrate:   0.24
CYP2D6-inhibitor:   0.886 CYP2D6-substrate:   0.993
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.998
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.882
HLM stability:   0.955
?
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):  3.149 Half-life (T1/2):  1.6

ADMET: Toxicity

hERG Blockers:  0.058 hERG Blockers (10um):  0.485
Human Hepatotoxicity (H-HT):  0.715 Drug-induced Liver Injury (DILI):  0.139
AMES Toxicity:  0.687 Rat Oral Acute Toxicity:  0.543
Maximum Recommended Daily Dose:  0.596 Skin Sensitization:  0.872
Carcinogencity:  0.498 Eye Corrosion:  0.028
Eye Irritation:  0.997 Respiratory Toxicity:  0.424
Drug-induced Neurotoxicity:  0.518 Ototoxicity:  0.325
Hematotoxicity:  0.116 Drug-induced Nephrotoxicity:  0.379
Genotoxicity:  0.954 RPMI-8226 Immunitoxicity:  0.137
A549 Cytotoxicity:  0.443 Hek293 Cytotoxicity:  0.707
BCF:   1.243
?
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:   3.888
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.656
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.215
?
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
NPO50059 Qualea labouriauana Genus Vochysiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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

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 NPC498322 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
1.0 High Similarity NPC603284
0.8 Intermediate Similarity NPC213322
0.7292 Intermediate Similarity NPC167624
0.7292 Intermediate Similarity NPC166482
0.6981 Remote Similarity NPC480991
0.6939 Remote Similarity NPC4743
0.6852 Remote Similarity NPC107572
0.6852 Remote Similarity NPC32739
0.6735 Remote Similarity NPC32441
0.6735 Remote Similarity NPC79943
0.6667 Remote Similarity NPC485881
0.64 Remote Similarity NPC482121
0.64 Remote Similarity NPC270964
0.6154 Remote Similarity NPC324386
0.6066 Remote Similarity NPC69531
0.5968 Remote Similarity NPC166934
0.5849 Remote Similarity NPC329203
0.5849 Remote Similarity NPC222342
0.5769 Remote Similarity NPC248372
0.5763 Remote Similarity NPC470133
0.5763 Remote Similarity NPC220998
0.5741 Remote Similarity NPC469764
0.5741 Remote Similarity NPC192083
0.5577 Remote Similarity NPC225153
0.5577 Remote Similarity NPC479876
0.5556 Remote Similarity NPC300668
0.5556 Remote Similarity NPC194432
0.5556 Remote Similarity NPC296917
0.5556 Remote Similarity NPC110776
0.5556 Remote Similarity NPC170907
0.5517 Remote Similarity NPC76372
0.5517 Remote Similarity NPC37496
0.55 Remote Similarity NPC66515
0.549 Remote Similarity NPC106914
0.549 Remote Similarity NPC329225
0.549 Remote Similarity NPC86502
0.549 Remote Similarity NPC147686
0.5472 Remote Similarity NPC243083
0.5472 Remote Similarity NPC13768
0.5472 Remote Similarity NPC287246
0.5455 Remote Similarity NPC321011
0.5455 Remote Similarity NPC224851
0.5455 Remote Similarity NPC294852
0.5455 Remote Similarity NPC188679
0.5455 Remote Similarity NPC475267
0.5455 Remote Similarity NPC606248
0.5424 Remote Similarity NPC324436
0.5424 Remote Similarity NPC78
0.541 Remote Similarity NPC134171
0.5333 Remote Similarity NPC265040
0.5333 Remote Similarity NPC148757
0.5273 Remote Similarity NPC274784
0.5273 Remote Similarity NPC20709
0.5273 Remote Similarity NPC110038
0.5254 Remote Similarity NPC164980
0.5231 Remote Similarity NPC51760
0.5224 Remote Similarity NPC479210
0.5211 Remote Similarity NPC475184
0.5185 Remote Similarity NPC295261
0.5185 Remote Similarity NPC296490
0.5179 Remote Similarity NPC324134
0.5179 Remote Similarity NPC40833
0.5161 Remote Similarity NPC76338
0.5161 Remote Similarity NPC250242
0.5091 Remote Similarity NPC20354
0.5091 Remote Similarity NPC188022
0.5091 Remote Similarity NPC177354
0.5088 Remote Similarity NPC2416
0.5088 Remote Similarity NPC271590
0.5085 Remote Similarity NPC236637
0.5082 Remote Similarity NPC477841
0.5077 Remote Similarity NPC611447
0.5075 Remote Similarity NPC475052
0.507 Remote Similarity NPC479054

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC498322 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
0.6735 Remote Similarity NPD1552 Clinical (unspecified phase)
0.5741 Remote Similarity NPD2393 Clinical (unspecified phase)
0.549 Remote Similarity NPD1549 Phase 2
0.5472 Remote Similarity NPD1550 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