Natural Product: NPC133392

Natural Product IDNPC133392
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5,7,3',4'-Tetrahydroxy-3-Methoxy-6-Geranylflavone
IUPAC Name 2-(3,4-dihydroxyphenyl)-6-[(2E)-3,7-dimethylocta-2,6-dienyl]-5,7-dihydroxy-3-methoxychromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL457262
PubChem CID 11015855
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001615] Flavones
          • [CHEMONTID:0003503] 6-prenylated flavones

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 SFMXXEOUUFGNQC-OVCLIPMQSA-N
Standard InCHI InChI=1S/C26H28O7/c1-14(2)6-5-7-15(3)8-10-17-19(28)13-21-22(23(17)30)24(31)26(32-4)25(33-21)16-9-11-18(27)20(29)12-16/h6,8-9,11-13,27-30H,5,7,10H2,1-4H3/b15-8+
SMILES CC(=CCC/C(=C/Cc1c(cc2c(c1O)c(=O)c(c(c1ccc(c(c1)O)O)o2)OC)O)/C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   452.18 Volume:   467.75
?
Van der Waals volume.
Dense:   0.967 LogP:   6.058
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.164
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.364
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   20.0
TPSA:   120.36
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.275 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.041 Fsp3:   0.269
MCE-18:   22.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.922 Fluc inhibitor:   0.38
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.959
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.888
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.195 Promiscuous compounds:   0.086

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.045 MDCK Permeability:   -4.74
Pgp-inhibitor:   0.967 Pgp-substrate:   0.001
PAMPA:   0.053
?
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):   0.017
20% Bioavailability (F20%):   0.616 30% Bioavailability (F30%):   0.937
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.907
Plasma Protein Binding (PPB):   97.131% Volume Distribution (VD):   -0.071
Fu: 2.825%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.967
OATP1B3 inhibitor:   0.993 BCRP inhibitor:   0.654
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   0.016 CYP1A2-substrate:   0.419
CYP2C19-inhibitor:   0.977 CYP2C19-substrate:   0.167
CYP2C9-inhibitor:   0.231 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.914 CYP2D6-substrate:   0.873
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.968
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):  7.354 Half-life (T1/2):  1.271

ADMET: Toxicity

hERG Blockers:  0.049 hERG Blockers (10um):  0.65
Human Hepatotoxicity (H-HT):  0.573 Drug-induced Liver Injury (DILI):  0.855
AMES Toxicity:  0.233 Rat Oral Acute Toxicity:  0.552
Maximum Recommended Daily Dose:  0.656 Skin Sensitization:  0.992
Carcinogencity:  0.417 Eye Corrosion:  0.01
Eye Irritation:  0.958 Respiratory Toxicity:  0.911
Drug-induced Neurotoxicity:  0.018 Ototoxicity:  0.404
Hematotoxicity:  0.087 Drug-induced Nephrotoxicity:  0.056
Genotoxicity:  0.942 RPMI-8226 Immunitoxicity:  0.061
A549 Cytotoxicity:  0.797 Hek293 Cytotoxicity:  0.532
BCF:   2.023
?
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:   5.243
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.68
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.249
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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
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. root n.a. PMID[11395279]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota whole plants Shawnee National Forest, Harrisburg, IL, US n.a. PMID[11678652]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota whole plants n.a. n.a. PMID[11678652]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. PMID[12419367]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota leaves Kaohsiung, Taiwan 2006-SEP PMID[18986201]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota Fruits n.a. n.a. PMID[19296617]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. formosan n.a. PMID[8864236]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. PMID[9358644]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO5495 Broussonetia papyrifera Species Moraceae 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
NPT441 Individual protein Cytochrome P450 19A1 Homo sapiens IC50 > 40.0 ug.mL-1 PMID[12880316]

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 NPC133392 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
0.7361 Intermediate Similarity NPC37684
0.7143 Intermediate Similarity NPC306488
0.6447 Remote Similarity NPC212932
0.6098 Remote Similarity NPC80534
0.6053 Remote Similarity NPC76833
0.589 Remote Similarity NPC157784
0.5811 Remote Similarity NPC3825
0.5732 Remote Similarity NPC40491
0.5732 Remote Similarity NPC278052
0.5679 Remote Similarity NPC262286
0.5647 Remote Similarity NPC488441
0.5625 Remote Similarity NPC236796
0.5526 Remote Similarity NPC488548
0.5443 Remote Similarity NPC68093
0.5417 Remote Similarity NPC286342
0.5417 Remote Similarity NPC214138
0.5417 Remote Similarity NPC163524
0.5402 Remote Similarity NPC7483
0.5402 Remote Similarity NPC74766
0.5349 Remote Similarity NPC478468
0.5309 Remote Similarity NPC269285
0.5309 Remote Similarity NPC602497
0.5244 Remote Similarity NPC227337
0.5181 Remote Similarity NPC320359
0.5165 Remote Similarity NPC237418
0.5065 Remote Similarity NPC24821
0.5065 Remote Similarity NPC284220
0.5062 Remote Similarity NPC97255

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC133392 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