Natural Product: NPC533814

Natural Product IDNPC533814
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2~{R})-5-hydroxy-6,7-dimethoxy-2-phenyl-chroman-4-one
IUPAC Name (2~{R})-5-hydroxy-6,7-dimethoxy-2-phenyl-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 FAUVORGACLCWKX-GFCCVEGCSA-N
Standard InCHI InChI=1S/C17H16O5/c1-20-14-9-13-15(16(19)17(14)21-2)11(18)8-12(22-13)10-6-4-3-5-7-10/h3-7,9,12,19H,8H2,1-2H3/t12-/m1/s1
SMILES COC1=CC2=C(C(=O)C[C@H](C3=CC=CC=C3)O2)C(O)=C1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.1 Volume:   302.415
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Van der Waals volume.
Dense:   0.992 LogP:   3.236
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.258
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.39
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   64.99
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Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.943 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.712 Fsp3:   0.235
MCE-18:   54.238
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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:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.313 Fluc inhibitor:   0.722
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.234
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.268
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.29 Promiscuous compounds:   0.045

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.909 MDCK Permeability:   -4.794
Pgp-inhibitor:   0.996 Pgp-substrate:   0.015
PAMPA:   0.031
?
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):   0.001
20% Bioavailability (F20%):   0.001 30% Bioavailability (F30%):   0.08
50% Bioavailability (F50%):   0.731

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.336 MRP1:   0.942
Plasma Protein Binding (PPB):   98.59% Volume Distribution (VD):   -0.232
Fu: 1.004%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.825
OATP1B3 inhibitor:   0.98 BCRP inhibitor:   0.877
BSEP inhibitor:   0.991

ADMET: Metabolism

CYP1A2-inhibitor:   0.171 CYP1A2-substrate:   0.923
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.898
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.003
CYP3A4-inhibitor:   0.067 CYP3A4-substrate:   0.465
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.627
HLM stability:   0.931
?
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):  5.484 Half-life (T1/2):  1.25

ADMET: Toxicity

hERG Blockers:  0.156 hERG Blockers (10um):  0.502
Human Hepatotoxicity (H-HT):  0.827 Drug-induced Liver Injury (DILI):  0.668
AMES Toxicity:  0.573 Rat Oral Acute Toxicity:  0.692
Maximum Recommended Daily Dose:  0.653 Skin Sensitization:  0.858
Carcinogencity:  0.378 Eye Corrosion:  0.098
Eye Irritation:  0.972 Respiratory Toxicity:  0.774
Drug-induced Neurotoxicity:  0.91 Ototoxicity:  0.345
Hematotoxicity:  0.358 Drug-induced Nephrotoxicity:  0.782
Genotoxicity:  0.834 RPMI-8226 Immunitoxicity:  0.152
A549 Cytotoxicity:  0.522 Hek293 Cytotoxicity:  0.33
BCF:   1.47
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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:   3.907
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.606
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.736
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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
NPO23939 Onychium siliculosum Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO46204 Mimulus aurantiacus Species Phrymaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO50639 Chrysothamnus nauseosus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23939 Onychium siliculosum Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23939 Onychium siliculosum 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 NPC533814 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
0.8125 Intermediate Similarity NPC475267
0.76 Intermediate Similarity NPC48208
0.76 Intermediate Similarity NPC601395
0.7 Intermediate Similarity NPC150648
0.6863 Remote Similarity NPC255106
0.6863 Remote Similarity NPC235165
0.68 Remote Similarity NPC482487
0.6346 Remote Similarity NPC37392
0.6078 Remote Similarity NPC265871
0.6078 Remote Similarity NPC205093
0.5926 Remote Similarity NPC194432
0.5849 Remote Similarity NPC243083
0.5849 Remote Similarity NPC13768
0.5849 Remote Similarity NPC6407
0.5849 Remote Similarity NPC287246
0.5849 Remote Similarity NPC204515
0.5849 Remote Similarity NPC545184
0.5741 Remote Similarity NPC312391
0.5741 Remote Similarity NPC162869
0.5714 Remote Similarity NPC228184
0.5667 Remote Similarity NPC95936
0.5636 Remote Similarity NPC99597
0.5636 Remote Similarity NPC482119
0.5636 Remote Similarity NPC480993
0.5636 Remote Similarity NPC482120
0.5636 Remote Similarity NPC215885
0.5636 Remote Similarity NPC329203
0.5636 Remote Similarity NPC110038
0.5636 Remote Similarity NPC222342
0.5577 Remote Similarity NPC485642
0.5577 Remote Similarity NPC611561
0.5536 Remote Similarity NPC606248
0.5455 Remote Similarity NPC177354
0.5439 Remote Similarity NPC18727
0.5439 Remote Similarity NPC2416
0.541 Remote Similarity NPC470178
0.537 Remote Similarity NPC476480
0.537 Remote Similarity NPC213322
0.537 Remote Similarity NPC84585
0.5323 Remote Similarity NPC470131
0.5323 Remote Similarity NPC470132
0.5273 Remote Similarity NPC248372
0.5273 Remote Similarity NPC482121
0.5273 Remote Similarity NPC270964
0.5246 Remote Similarity NPC1089
0.5246 Remote Similarity NPC109183
0.52 Remote Similarity NPC314329
0.52 Remote Similarity NPC603208
0.5172 Remote Similarity NPC271590
0.5161 Remote Similarity NPC175504
0.5161 Remote Similarity NPC250214
0.5091 Remote Similarity NPC22467
0.5091 Remote Similarity NPC225153
0.5091 Remote Similarity NPC188243
0.5091 Remote Similarity NPC479876
0.5091 Remote Similarity NPC110228
0.5088 Remote Similarity NPC274784
0.5088 Remote Similarity NPC73028
0.5088 Remote Similarity NPC20709
0.5088 Remote Similarity NPC110776
0.5079 Remote Similarity NPC281549

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC533814 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 NPD1550 Phase 2
0.52 Remote Similarity NPD1547 Clinical (unspecified phase)

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