Natural Product: NPC291878

Natural Product IDNPC291878
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2S)-5,7,3'-Trihydroxy-4'-Methoxy-8-(3''-Methylbut-2''-Enyl)-Flavonone
IUPAC Name (2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-8-(3-methylbut-2-enyl)-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1689340
PubChem CID 14259001
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003642] 8-prenylated flavans
            • [CHEMONTID:0003508] 8-prenylated 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 MDRKJMLXLVCUIU-IBGZPJMESA-N
Standard InCHI InChI=1S/C21H22O6/c1-11(2)4-6-13-14(22)9-16(24)20-17(25)10-19(27-21(13)20)12-5-7-18(26-3)15(23)8-12/h4-5,7-9,19,22-24H,6,10H2,1-3H3/t19-/m0/s1
SMILES COc1ccc(cc1O)[C@@H]1CC(=O)c2c(O1)c(CC=C(C)C)c(cc2O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   370.14 Volume:   377.752
?
Van der Waals volume.
Dense:   0.98 LogP:   3.816
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.305
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.844
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   96.22
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.703 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.277 Fsp3:   0.286
MCE-18:   62.963
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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:   0
Colloidal aggregators:   0.782 Fluc inhibitor:   0.843
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.566
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.55
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.301 Promiscuous compounds:   0.157

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.022 MDCK Permeability:   -4.766
Pgp-inhibitor:   0.813 Pgp-substrate:   0.048
PAMPA:   0.025
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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):   0.034
20% Bioavailability (F20%):   0.906 30% Bioavailability (F30%):   0.997
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.939
Plasma Protein Binding (PPB):   96.162% Volume Distribution (VD):   0.086
Fu: 3.094%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.995
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.994
BSEP inhibitor:   0.496

ADMET: Metabolism

CYP1A2-inhibitor:   0.121 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.776 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.511 CYP2C9-substrate:   0.008
CYP2D6-inhibitor:   0.143 CYP2D6-substrate:   0.11
CYP3A4-inhibitor:   0.105 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  3.484 Half-life (T1/2):  1.74

ADMET: Toxicity

hERG Blockers:  0.05 hERG Blockers (10um):  0.462
Human Hepatotoxicity (H-HT):  0.751 Drug-induced Liver Injury (DILI):  0.873
AMES Toxicity:  0.819 Rat Oral Acute Toxicity:  0.875
Maximum Recommended Daily Dose:  0.761 Skin Sensitization:  0.974
Carcinogencity:  0.541 Eye Corrosion:  0.001
Eye Irritation:  0.902 Respiratory Toxicity:  0.984
Drug-induced Neurotoxicity:  0.636 Ototoxicity:  0.494
Hematotoxicity:  0.232 Drug-induced Nephrotoxicity:  0.883
Genotoxicity:  0.985 RPMI-8226 Immunitoxicity:  0.205
A549 Cytotoxicity:  0.86 Hek293 Cytotoxicity:  0.669
BCF:   1.75
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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:   4.417
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.776
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.144
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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
NPO3499 Macaranga conifera Species Euphorbiaceae Eukaryota n.a. leaf n.a. DOI[10.1016/S0031-9422(02)00378-3]
NPO3499 Macaranga conifera Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[21275386]
NPO3499 Macaranga conifera Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3499 Macaranga conifera Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3499 Macaranga conifera Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3499 Macaranga conifera Species Euphorbiaceae 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
NPT1422 Individual protein ATP-binding cassette sub-family G member 2 Homo sapiens IC50 = 6600.0 nM PMID[21275386]

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 NPC291878 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
0.8276 Intermediate Similarity NPC480990
0.8103 Intermediate Similarity NPC148757
0.7581 Intermediate Similarity NPC161506
0.7458 Intermediate Similarity NPC76372
0.7458 Intermediate Similarity NPC37496
0.7333 Intermediate Similarity NPC107572
0.7333 Intermediate Similarity NPC32739
0.7143 Intermediate Similarity NPC485610
0.7097 Intermediate Similarity NPC66515
0.7031 Intermediate Similarity NPC36217
0.6774 Remote Similarity NPC324436
0.6774 Remote Similarity NPC78
0.6774 Remote Similarity NPC306829
0.6479 Remote Similarity NPC192686
0.6364 Remote Similarity NPC182852
0.6324 Remote Similarity NPC24136
0.6232 Remote Similarity NPC166934
0.6029 Remote Similarity NPC10990
0.6 Remote Similarity NPC300988
0.6 Remote Similarity NPC484417
0.5909 Remote Similarity NPC149026
0.5909 Remote Similarity NPC250214
0.5873 Remote Similarity NPC302950
0.5821 Remote Similarity NPC610133
0.5714 Remote Similarity NPC28918
0.5672 Remote Similarity NPC187282
0.56 Remote Similarity NPC278778
0.5588 Remote Similarity NPC220998
0.5507 Remote Similarity NPC76338
0.5507 Remote Similarity NPC250242
0.5469 Remote Similarity NPC18727
0.5441 Remote Similarity NPC265040
0.5429 Remote Similarity NPC608140
0.5385 Remote Similarity NPC479054
0.5373 Remote Similarity NPC164980
0.5373 Remote Similarity NPC480991
0.5362 Remote Similarity NPC17170
0.5362 Remote Similarity NPC310130
0.5294 Remote Similarity NPC236766
0.5294 Remote Similarity NPC150408
0.5286 Remote Similarity NPC285555
0.5256 Remote Similarity NPC218226
0.5256 Remote Similarity NPC488557
0.5231 Remote Similarity NPC48208
0.5217 Remote Similarity NPC69674
0.5139 Remote Similarity NPC485620
0.5128 Remote Similarity NPC119209
0.5072 Remote Similarity NPC91560
0.5068 Remote Similarity NPC200761
0.5068 Remote Similarity NPC473078
0.5067 Remote Similarity NPC484416

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC291878 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
0.5873 Remote Similarity NPD1934 Phase 0

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