Natural Product: NPC233056

Natural Product IDNPC233056
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3'-Hydroxyphloretin
IUPAC Name 3-(3,4-dihydroxyphenyl)-1-(2,4,6-trihydroxyphenyl)propan-1-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL492818
PubChem CID 11778945
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003467] Linear 1,3-diarylpropanoids
        • [CHEMONTID:0001630] Chalcones and dihydrochalcones
          • [CHEMONTID:0003473] 2'-Hydroxy-dihydrochalcones

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 CNABJBYLQABXJR-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H14O6/c16-9-6-13(20)15(14(21)7-9)11(18)4-2-8-1-3-10(17)12(19)5-8/h1,3,5-7,16-17,19-21H,2,4H2
SMILES c1cc(c(cc1CCC(=O)c1c(cc(cc1O)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   290.08 Volume:   285.169
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Van der Waals volume.
Dense:   1.017 LogP:   1.951
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.288
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.831
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   13.0
TPSA:   118.22
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   5.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.434 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.356 Fsp3:   0.133
MCE-18:   14.0
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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:   1 PAINS Alert:   1
Colloidal aggregators:   0.76 Fluc inhibitor:   0.504
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.181
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.132
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.685 Promiscuous compounds:   0.138

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.95 MDCK Permeability:   -4.829
Pgp-inhibitor:   0.076 Pgp-substrate:   0.007
PAMPA:   0.214
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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):   0.001
20% Bioavailability (F20%):   0.277 30% Bioavailability (F30%):   0.98
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.005 MRP1:   0.889
Plasma Protein Binding (PPB):   94.539% Volume Distribution (VD):   -0.524
Fu: 4.98%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.993
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.808
BSEP inhibitor:   0.337

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.994
CYP2C19-inhibitor:   0.278 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.998
CYP2D6-inhibitor:   0.969 CYP2D6-substrate:   0.998
CYP3A4-inhibitor:   0.021 CYP3A4-substrate:   0.956
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.999
?
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):  11.835 Half-life (T1/2):  1.431

ADMET: Toxicity

hERG Blockers:  0.071 hERG Blockers (10um):  0.712
Human Hepatotoxicity (H-HT):  0.376 Drug-induced Liver Injury (DILI):  0.045
AMES Toxicity:  0.364 Rat Oral Acute Toxicity:  0.312
Maximum Recommended Daily Dose:  0.72 Skin Sensitization:  0.964
Carcinogencity:  0.254 Eye Corrosion:  0.132
Eye Irritation:  0.996 Respiratory Toxicity:  0.892
Drug-induced Neurotoxicity:  0.057 Ototoxicity:  0.309
Hematotoxicity:  0.049 Drug-induced Nephrotoxicity:  0.028
Genotoxicity:  0.941 RPMI-8226 Immunitoxicity:  0.015
A549 Cytotoxicity:  0.771 Hek293 Cytotoxicity:  0.628
BCF:   1.355
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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:   3.737
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.946
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.223
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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
NPO33072 smilax glyciphylla Species n.a. Eukaryota n.a. Australian n.a. PMID[24050300]

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
NPT741 Individual protein Tyrosinase Homo sapiens IC50 = 32000.0 nM PMID[32787103]
NPT441 Individual protein Cytochrome P450 19A1 Homo sapiens IC50 = 2798.98 nM PMID[28622580]

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. Activity = 0.0 % PMID[521818]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 95.0 % PMID[521818]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 0.88 equiv PMID[24050300]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 0.64 equiv PMID[24050300]

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 NPC233056 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
0.7895 Intermediate Similarity NPC242895
0.7 Intermediate Similarity NPC607946
0.6364 Remote Similarity NPC604715
0.5814 Remote Similarity NPC133909
0.58 Remote Similarity NPC601405
0.5652 Remote Similarity NPC82225
0.5636 Remote Similarity NPC267846
0.551 Remote Similarity NPC244441
0.5439 Remote Similarity NPC116513
0.5319 Remote Similarity NPC175552
0.5217 Remote Similarity NPC156139
0.5217 Remote Similarity NPC179494

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC233056 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