Natural Product: NPC492088

Natural Product IDNPC492088
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2~{R})-7-hydroxy-5-methoxy-2-(4-methoxyphenyl)chroman-4-one
IUPAC Name (2~{R})-7-hydroxy-5-methoxy-2-(4-methoxyphenyl)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 KFGFEKHSEPSVNO-CQSZACIVSA-N
Standard InCHI InChI=1S/C17H16O5/c1-20-12-5-3-10(4-6-12)14-9-13(19)17-15(21-2)7-11(18)8-16(17)22-14/h3-8,14,18H,9H2,1-2H3/t14-/m1/s1
SMILES COC1=CC=C([C@H]2CC(=O)C3=C(OC)C=C(O)C=C3O2)C=C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.1 Volume:   302.415
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Van der Waals volume.
Dense:   0.992 LogP:   2.897
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.994
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.421
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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:   2.679 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:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.424 Fluc inhibitor:   0.928
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.278
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.339
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.326 Promiscuous compounds:   0.069

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.832 MDCK Permeability:   -4.758
Pgp-inhibitor:   0.976 Pgp-substrate:   0.018
PAMPA:   0.033
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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):   0.007
20% Bioavailability (F20%):   0.004 30% Bioavailability (F30%):   0.509
50% Bioavailability (F50%):   0.98

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.693
Plasma Protein Binding (PPB):   96.603% Volume Distribution (VD):   0.179
Fu: 3.453%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.991
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.992
BSEP inhibitor:   0.995

ADMET: Metabolism

CYP1A2-inhibitor:   0.996 CYP1A2-substrate:   0.988
CYP2C19-inhibitor:   0.994 CYP2C19-substrate:   0.997
CYP2C9-inhibitor:   0.901 CYP2C9-substrate:   0.005
CYP2D6-inhibitor:   0.847 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.278 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.178
HLM stability:   0.883
?
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):  7.244 Half-life (T1/2):  1.057

ADMET: Toxicity

hERG Blockers:  0.249 hERG Blockers (10um):  0.527
Human Hepatotoxicity (H-HT):  0.694 Drug-induced Liver Injury (DILI):  0.558
AMES Toxicity:  0.779 Rat Oral Acute Toxicity:  0.421
Maximum Recommended Daily Dose:  0.599 Skin Sensitization:  0.364
Carcinogencity:  0.819 Eye Corrosion:  0.093
Eye Irritation:  0.99 Respiratory Toxicity:  0.339
Drug-induced Neurotoxicity:  0.853 Ototoxicity:  0.274
Hematotoxicity:  0.322 Drug-induced Nephrotoxicity:  0.598
Genotoxicity:  0.758 RPMI-8226 Immunitoxicity:  0.106
A549 Cytotoxicity:  0.164 Hek293 Cytotoxicity:  0.515
BCF:   1.448
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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:   3.983
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.572
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.756
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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
NPO5154 Tsuga diversifolia Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO583 Goniothalamus gardneri Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO583 Goniothalamus gardneri Species Annonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO583 Goniothalamus gardneri Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5154 Tsuga diversifolia Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO583 Goniothalamus gardneri Species Annonaceae 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 NPC492088 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
1.0 High Similarity NPC188243
1.0 High Similarity NPC110228
0.8372 Intermediate Similarity NPC265871
0.8372 Intermediate Similarity NPC205093
0.8182 Intermediate Similarity NPC225153
0.8182 Intermediate Similarity NPC479876
0.6939 Remote Similarity NPC274784
0.6939 Remote Similarity NPC20709
0.6889 Remote Similarity NPC99854
0.66 Remote Similarity NPC156057
0.6531 Remote Similarity NPC6407
0.6531 Remote Similarity NPC545184
0.6122 Remote Similarity NPC135616
0.6078 Remote Similarity NPC177354
0.5769 Remote Similarity NPC150648
0.5769 Remote Similarity NPC162869
0.5745 Remote Similarity NPC228184
0.5741 Remote Similarity NPC469758
0.5686 Remote Similarity NPC476480
0.5686 Remote Similarity NPC84585
0.566 Remote Similarity NPC296917
0.566 Remote Similarity NPC329203
0.566 Remote Similarity NPC222342
0.566 Remote Similarity NPC170907
0.56 Remote Similarity NPC329225
0.56 Remote Similarity NPC147686
0.5577 Remote Similarity NPC243083
0.5577 Remote Similarity NPC13768
0.5577 Remote Similarity NPC36016
0.5577 Remote Similarity NPC287246
0.5472 Remote Similarity NPC20354
0.5455 Remote Similarity NPC599987
0.537 Remote Similarity NPC99597
0.537 Remote Similarity NPC255106
0.537 Remote Similarity NPC235165
0.5357 Remote Similarity NPC302950
0.5294 Remote Similarity NPC485642
0.5294 Remote Similarity NPC611561
0.5283 Remote Similarity NPC32441
0.5283 Remote Similarity NPC79943
0.5273 Remote Similarity NPC476153
0.5273 Remote Similarity NPC606248
0.5185 Remote Similarity NPC37392
0.5179 Remote Similarity NPC18727
0.5091 Remote Similarity NPC194432
0.5091 Remote Similarity NPC73028
0.5091 Remote Similarity NPC480993
0.5091 Remote Similarity NPC338131
0.5082 Remote Similarity NPC470133
0.5072 Remote Similarity NPC5778

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC492088 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
0.56 Remote Similarity NPD1549 Phase 2
0.5577 Remote Similarity NPD1550 Phase 2
0.5357 Remote Similarity NPD1934 Phase 0
0.5283 Remote Similarity NPD1552 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