Natural Product: NPC594172

Natural Product IDNPC594172
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2~{S})-5-hydroxy-2-(4-hydroxyphenyl)-6,7,8-trimethoxy-chroman-4-one
IUPAC Name (2~{S})-5-hydroxy-2-(4-hydroxyphenyl)-6,7,8-trimethoxy-chroman-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 TZVHQZKWRMUZBY-LBPRGKRZSA-N
Standard InCHI InChI=1S/C18H18O7/c1-22-16-14(21)13-11(20)8-12(9-4-6-10(19)7-5-9)25-15(13)17(23-2)18(16)24-3/h4-7,12,19,21H,8H2,1-3H3/t12-/m0/s1
SMILES COC1=C(O)C2=C(O[C@H](C3=CC=C(O)C=C3)CC2=O)C(OC)=C1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   346.11 Volume:   337.291
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Van der Waals volume.
Dense:   1.026 LogP:   2.655
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.805
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.274
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   94.45
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Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.879 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.036 Fsp3:   0.278
MCE-18:   60.304
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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:   0.297 Fluc inhibitor:   0.55
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.263
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.315
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.296 Promiscuous compounds:   0.079

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.012 MDCK Permeability:   -4.787
Pgp-inhibitor:   0.294 Pgp-substrate:   0.133
PAMPA:   0.236
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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):   0.0
20% Bioavailability (F20%):   0.006 30% Bioavailability (F30%):   0.113
50% Bioavailability (F50%):   0.842

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.031 MRP1:   0.995
Plasma Protein Binding (PPB):   95.548% Volume Distribution (VD):   -0.449
Fu: 4.359%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.266
OATP1B3 inhibitor:   0.957 BCRP inhibitor:   0.877
BSEP inhibitor:   0.885

ADMET: Metabolism

CYP1A2-inhibitor:   0.62 CYP1A2-substrate:   0.124
CYP2C19-inhibitor:   0.087 CYP2C19-substrate:   0.723
CYP2C9-inhibitor:   0.007 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.01 CYP2D6-substrate:   0.01
CYP3A4-inhibitor:   0.832 CYP3A4-substrate:   0.889
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.837
HLM stability:   0.947
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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):  6.163 Half-life (T1/2):  1.157

ADMET: Toxicity

hERG Blockers:  0.149 hERG Blockers (10um):  0.544
Human Hepatotoxicity (H-HT):  0.757 Drug-induced Liver Injury (DILI):  0.567
AMES Toxicity:  0.457 Rat Oral Acute Toxicity:  0.647
Maximum Recommended Daily Dose:  0.676 Skin Sensitization:  0.909
Carcinogencity:  0.465 Eye Corrosion:  0.084
Eye Irritation:  0.966 Respiratory Toxicity:  0.836
Drug-induced Neurotoxicity:  0.871 Ototoxicity:  0.352
Hematotoxicity:  0.276 Drug-induced Nephrotoxicity:  0.604
Genotoxicity:  0.829 RPMI-8226 Immunitoxicity:  0.176
A549 Cytotoxicity:  0.678 Hek293 Cytotoxicity:  0.644
BCF:   1.122
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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:   3.553
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.676
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.996
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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
NPO26899 Cheilanthes argentea Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26899 Cheilanthes argentea Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26899 Cheilanthes argentea Species Pteridaceae 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

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 NPC594172 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
0.8085 Intermediate Similarity NPC162869
0.7059 Intermediate Similarity NPC475267
0.6415 Remote Similarity NPC606248
0.6226 Remote Similarity NPC329203
0.6226 Remote Similarity NPC222342
0.5962 Remote Similarity NPC225153
0.5962 Remote Similarity NPC479876
0.5849 Remote Similarity NPC32441
0.5849 Remote Similarity NPC79943
0.5818 Remote Similarity NPC485881
0.5741 Remote Similarity NPC37392
0.5636 Remote Similarity NPC300668
0.5636 Remote Similarity NPC324386
0.5577 Remote Similarity NPC329225
0.5577 Remote Similarity NPC147686
0.5556 Remote Similarity NPC482487
0.5556 Remote Similarity NPC603284
0.5536 Remote Similarity NPC469764
0.5536 Remote Similarity NPC210084
0.5455 Remote Similarity NPC167624
0.5455 Remote Similarity NPC166482
0.541 Remote Similarity NPC69674
0.5323 Remote Similarity NPC470131
0.5323 Remote Similarity NPC470133
0.5323 Remote Similarity NPC220998
0.5323 Remote Similarity NPC470132
0.5238 Remote Similarity NPC486094
0.5172 Remote Similarity NPC48208
0.5172 Remote Similarity NPC601395
0.5161 Remote Similarity NPC95936
0.5088 Remote Similarity NPC274784
0.5088 Remote Similarity NPC255106
0.5088 Remote Similarity NPC20709
0.5088 Remote Similarity NPC235165
0.5088 Remote Similarity NPC610021
0.5082 Remote Similarity NPC169591
0.5082 Remote Similarity NPC298223
0.5082 Remote Similarity NPC604412

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC594172 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
0.5849 Remote Similarity NPD1552 Clinical (unspecified phase)
0.5577 Remote Similarity NPD1549 Phase 2

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