Natural Product: NPC55619

Natural Product IDNPC55619
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Chrysosplenol F
IUPAC Name 2-(2,4-dihydroxy-5-methoxyphenyl)-5-hydroxy-3,7-dimethoxychromen-4-one
Synonyms chrysosplenol F
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL484866
PubChem CID 5491448
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 FJFLYDSOXABNGE-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O8/c1-23-8-4-12(21)15-14(5-8)26-17(18(25-3)16(15)22)9-6-13(24-2)11(20)7-10(9)19/h4-7,19-21H,1-3H3
SMILES COc1cc(c2c(c1)oc(c1cc(c(cc1O)O)OC)c(c2=O)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   360.08 Volume:   343.445
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Van der Waals volume.
Dense:   1.048 LogP:   2.314
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.342
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.363
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   118.59
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Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.65 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.565 Fsp3:   0.167
MCE-18:   20.0
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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:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.371 Fluc inhibitor:   0.328
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.851
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.65
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.388 Promiscuous compounds:   0.811

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.227 MDCK Permeability:   -4.803
Pgp-inhibitor:   0.982 Pgp-substrate:   0.201
PAMPA:   0.035
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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):   0.102
20% Bioavailability (F20%):   0.014 30% Bioavailability (F30%):   0.176
50% Bioavailability (F50%):   0.971

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.67
Plasma Protein Binding (PPB):   95.89% Volume Distribution (VD):   -0.446
Fu: 4.329%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.721
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.99
BSEP inhibitor:   0.993

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.573
CYP2C19-inhibitor:   0.268 CYP2C19-substrate:   0.062
CYP2C9-inhibitor:   0.814 CYP2C9-substrate:   0.352
CYP2D6-inhibitor:   0.983 CYP2D6-substrate:   0.822
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.933
HLM stability:   0.961
?
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):  1.769 Half-life (T1/2):  1.862

ADMET: Toxicity

hERG Blockers:  0.059 hERG Blockers (10um):  0.474
Human Hepatotoxicity (H-HT):  0.391 Drug-induced Liver Injury (DILI):  0.719
AMES Toxicity:  0.583 Rat Oral Acute Toxicity:  0.427
Maximum Recommended Daily Dose:  0.6 Skin Sensitization:  0.55
Carcinogencity:  0.741 Eye Corrosion:  0.359
Eye Irritation:  0.987 Respiratory Toxicity:  0.815
Drug-induced Neurotoxicity:  0.072 Ototoxicity:  0.117
Hematotoxicity:  0.17 Drug-induced Nephrotoxicity:  0.105
Genotoxicity:  0.615 RPMI-8226 Immunitoxicity:  0.112
A549 Cytotoxicity:  0.299 Hek293 Cytotoxicity:  0.515
BCF:   0.947
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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:   3.696
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.261
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.623
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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
NPO12348 Chrysosplenium grayanum Species Saxifragaceae Eukaryota n.a. n.a. n.a. PMID[1955888]
NPO12348 Chrysosplenium grayanum Species Saxifragaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12348 Chrysosplenium grayanum Species Saxifragaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12348 Chrysosplenium grayanum Species Saxifragaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12348 Chrysosplenium grayanum Species Saxifragaceae 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
NPT91 Cell line KB Homo sapiens ED50 > 25.0 ug ml-1 PMID[9873651]

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 NPC55619 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
0.7636 Intermediate Similarity NPC246204
0.7636 Intermediate Similarity NPC200388
0.7143 Intermediate Similarity NPC100916
0.7069 Intermediate Similarity NPC78326
0.6724 Remote Similarity NPC270620
0.6667 Remote Similarity NPC76376
0.661 Remote Similarity NPC58382
0.661 Remote Similarity NPC206604
0.6491 Remote Similarity NPC103904
0.6491 Remote Similarity NPC262094
0.6379 Remote Similarity NPC146679
0.6379 Remote Similarity NPC188871
0.6333 Remote Similarity NPC236769
0.5846 Remote Similarity NPC99671
0.5645 Remote Similarity NPC604677
0.5556 Remote Similarity NPC124784
0.5469 Remote Similarity NPC252933
0.5469 Remote Similarity NPC137062
0.5397 Remote Similarity NPC200740
0.5397 Remote Similarity NPC328119
0.5323 Remote Similarity NPC48479
0.5312 Remote Similarity NPC177298
0.5312 Remote Similarity NPC223579
0.5231 Remote Similarity NPC279989
0.5156 Remote Similarity NPC153758
0.5079 Remote Similarity NPC33265
0.5079 Remote Similarity NPC87125
0.5079 Remote Similarity NPC605755
0.5077 Remote Similarity NPC18607

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC55619 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