Natural Product: NPC100916

Natural Product IDNPC100916
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Chrysosplenol G
IUPAC Name 5-hydroxy-2-(5-hydroxy-2,4-dimethoxyphenyl)-3,7-dimethoxychromen-4-one
Synonyms chrysosplenol G
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL483030
PubChem CID 5315858
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 DCBXANRVINYQLF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H18O8/c1-23-9-5-12(21)16-15(6-9)27-18(19(26-4)17(16)22)10-7-11(20)14(25-3)8-13(10)24-2/h5-8,20-21H,1-4H3
SMILES COc1cc(c2c(c1)oc(c1cc(c(cc1OC)OC)O)c(c2=O)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   374.1 Volume:   360.741
?
Van der Waals volume.
Dense:   1.037 LogP:   2.328
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.355
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.726
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   18.0
TPSA:   107.59
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.702 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.492 Fsp3:   0.211
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:   0.201 Fluc inhibitor:   0.292
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.858
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.639
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.353 Promiscuous compounds:   0.756

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.172 MDCK Permeability:   -4.744
Pgp-inhibitor:   0.977 Pgp-substrate:   0.199
PAMPA:   0.015
?
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):   0.165
20% Bioavailability (F20%):   0.017 30% Bioavailability (F30%):   0.195
50% Bioavailability (F50%):   0.987

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.629
Plasma Protein Binding (PPB):   89.812% Volume Distribution (VD):   -0.533
Fu: 9.476%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.947
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.997
BSEP inhibitor:   0.989

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   0.547
CYP2C19-inhibitor:   0.704 CYP2C19-substrate:   0.177
CYP2C9-inhibitor:   0.996 CYP2C9-substrate:   0.462
CYP2D6-inhibitor:   0.992 CYP2D6-substrate:   0.99
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.01
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.822
HLM stability:   0.939
?
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):  4.579 Half-life (T1/2):  1.559

ADMET: Toxicity

hERG Blockers:  0.08 hERG Blockers (10um):  0.481
Human Hepatotoxicity (H-HT):  0.433 Drug-induced Liver Injury (DILI):  0.778
AMES Toxicity:  0.537 Rat Oral Acute Toxicity:  0.431
Maximum Recommended Daily Dose:  0.556 Skin Sensitization:  0.476
Carcinogencity:  0.744 Eye Corrosion:  0.392
Eye Irritation:  0.976 Respiratory Toxicity:  0.785
Drug-induced Neurotoxicity:  0.139 Ototoxicity:  0.144
Hematotoxicity:  0.282 Drug-induced Nephrotoxicity:  0.146
Genotoxicity:  0.52 RPMI-8226 Immunitoxicity:  0.111
A549 Cytotoxicity:  0.198 Hek293 Cytotoxicity:  0.418
BCF:   0.99
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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:   3.561
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.283
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.726
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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 = 8.61 ug ml-1 PMID[1955888]

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 NPC100916 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
0.7273 Intermediate Similarity NPC200388
0.7143 Intermediate Similarity NPC55619
0.6964 Remote Similarity NPC270620
0.6727 Remote Similarity NPC103904
0.6727 Remote Similarity NPC262094
0.6724 Remote Similarity NPC78326
0.6607 Remote Similarity NPC76376
0.6607 Remote Similarity NPC146679
0.6607 Remote Similarity NPC188871
0.6552 Remote Similarity NPC58382
0.6552 Remote Similarity NPC206604
0.6379 Remote Similarity NPC246204
0.6271 Remote Similarity NPC236769
0.5781 Remote Similarity NPC99671
0.5574 Remote Similarity NPC200740
0.5574 Remote Similarity NPC328119
0.5484 Remote Similarity NPC223579
0.5323 Remote Similarity NPC153758
0.5246 Remote Similarity NPC48479
0.5246 Remote Similarity NPC87125
0.5246 Remote Similarity NPC605755
0.5238 Remote Similarity NPC177298
0.5161 Remote Similarity NPC108406
0.5156 Remote Similarity NPC252933
0.5156 Remote Similarity NPC137062
0.5082 Remote Similarity NPC127447
0.5082 Remote Similarity NPC152042
0.5082 Remote Similarity NPC29353
0.5079 Remote Similarity NPC300943
0.5079 Remote Similarity NPC605582

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC100916 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