Natural Product: NPC507811

Natural Product IDNPC507811
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)-7-methoxy-8-methyl-chroman-4-one
IUPAC Name (2~{S})-5-hydroxy-2-(4-hydroxyphenyl)-7-methoxy-8-methyl-chroman-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
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 SLKIIKQMXLBVTD-HNNXBMFYSA-N
Standard InCHI InChI=1S/C17H16O5/c1-9-14(21-2)7-12(19)16-13(20)8-15(22-17(9)16)10-3-5-11(18)6-4-10/h3-7,15,18-19H,8H2,1-2H3/t15-/m0/s1
SMILES COC1=CC(O)=C2C(=O)C[C@@H](C3=CC=C(O)C=C3)OC2=C1C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.1 Volume:   302.415
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Van der Waals volume.
Dense:   0.992 LogP:   3.217
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.073
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.487
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   75.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.891 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.918 Fsp3:   0.235
MCE-18:   57.429
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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:   0.608 Fluc inhibitor:   0.848
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.26
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.368
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.293 Promiscuous compounds:   0.064

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.918 MDCK Permeability:   -4.776
Pgp-inhibitor:   0.408 Pgp-substrate:   0.481
PAMPA:   0.037
?
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%):   0.001 30% Bioavailability (F30%):   0.073
50% Bioavailability (F50%):   0.875

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.984
Plasma Protein Binding (PPB):   95.996% Volume Distribution (VD):   -0.018
Fu: 3.342%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.278
OATP1B3 inhibitor:   0.952 BCRP inhibitor:   0.964
BSEP inhibitor:   0.965

ADMET: Metabolism

CYP1A2-inhibitor:   0.691 CYP1A2-substrate:   0.847
CYP2C19-inhibitor:   0.006 CYP2C19-substrate:   0.975
CYP2C9-inhibitor:   0.069 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.615 CYP2D6-substrate:   0.229
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.998
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.475
HLM stability:   0.695
?
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):  10.233 Half-life (T1/2):  1.081

ADMET: Toxicity

hERG Blockers:  0.119 hERG Blockers (10um):  0.481
Human Hepatotoxicity (H-HT):  0.79 Drug-induced Liver Injury (DILI):  0.512
AMES Toxicity:  0.634 Rat Oral Acute Toxicity:  0.699
Maximum Recommended Daily Dose:  0.725 Skin Sensitization:  0.861
Carcinogencity:  0.46 Eye Corrosion:  0.095
Eye Irritation:  0.988 Respiratory Toxicity:  0.855
Drug-induced Neurotoxicity:  0.789 Ototoxicity:  0.352
Hematotoxicity:  0.225 Drug-induced Nephrotoxicity:  0.655
Genotoxicity:  0.948 RPMI-8226 Immunitoxicity:  0.133
A549 Cytotoxicity:  0.606 Hek293 Cytotoxicity:  0.57
BCF:   1.209
?
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:   3.906
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.844
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.333
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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
NPO23149 Callistemon coccineus Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO50072 Callistemon Genus Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO57793 Callistemon acuminatus Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23149 Callistemon coccineus Species Myrtaceae 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 NPC507811 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 NPC194432
0.7255 Intermediate Similarity NPC485881
0.7 Intermediate Similarity NPC603284
0.6842 Remote Similarity NPC470133
0.6842 Remote Similarity NPC220998
0.6731 Remote Similarity NPC329203
0.6731 Remote Similarity NPC324386
0.6731 Remote Similarity NPC222342
0.6415 Remote Similarity NPC17809
0.6346 Remote Similarity NPC32441
0.6346 Remote Similarity NPC79943
0.6296 Remote Similarity NPC606248
0.6226 Remote Similarity NPC167624
0.6226 Remote Similarity NPC166482
0.6154 Remote Similarity NPC225153
0.6154 Remote Similarity NPC479876
0.6111 Remote Similarity NPC300668
0.6 Remote Similarity NPC475267
0.5932 Remote Similarity NPC109183
0.5926 Remote Similarity NPC177354
0.5902 Remote Similarity NPC76338
0.5902 Remote Similarity NPC250242
0.5833 Remote Similarity NPC175504
0.5818 Remote Similarity NPC215885
0.5818 Remote Similarity NPC110038
0.5769 Remote Similarity NPC329225
0.5769 Remote Similarity NPC147686
0.5763 Remote Similarity NPC480991
0.5714 Remote Similarity NPC469764
0.5667 Remote Similarity NPC107572
0.5667 Remote Similarity NPC32739
0.5645 Remote Similarity NPC134171
0.5636 Remote Similarity NPC188022
0.5636 Remote Similarity NPC134195
0.5556 Remote Similarity NPC213322
0.5538 Remote Similarity NPC69531
0.5536 Remote Similarity NPC274784
0.5536 Remote Similarity NPC20709
0.5522 Remote Similarity NPC475052
0.5484 Remote Similarity NPC470131
0.5484 Remote Similarity NPC470135
0.5484 Remote Similarity NPC470132
0.5455 Remote Similarity NPC51760
0.5455 Remote Similarity NPC6407
0.5455 Remote Similarity NPC545184
0.5441 Remote Similarity NPC479210
0.5439 Remote Similarity NPC210084
0.5357 Remote Similarity NPC150648
0.5357 Remote Similarity NPC312391
0.5357 Remote Similarity NPC37392
0.5333 Remote Similarity NPC236637
0.5323 Remote Similarity NPC69674
0.5303 Remote Similarity NPC301276
0.5294 Remote Similarity NPC485619
0.5263 Remote Similarity NPC296917
0.5263 Remote Similarity NPC170907
0.5238 Remote Similarity NPC176229
0.5205 Remote Similarity NPC475184
0.5179 Remote Similarity NPC243083
0.5179 Remote Similarity NPC13768
0.5179 Remote Similarity NPC482121
0.5179 Remote Similarity NPC287246
0.5179 Remote Similarity NPC270964
0.5172 Remote Similarity NPC321011
0.5172 Remote Similarity NPC294852
0.5172 Remote Similarity NPC480992
0.5172 Remote Similarity NPC188679
0.5161 Remote Similarity NPC39329
0.5161 Remote Similarity NPC51032
0.5156 Remote Similarity NPC486094
0.5091 Remote Similarity NPC265871
0.5091 Remote Similarity NPC205093
0.5088 Remote Similarity NPC4743
0.5085 Remote Similarity NPC310135
0.5085 Remote Similarity NPC2416
0.5079 Remote Similarity NPC265040
0.5075 Remote Similarity NPC611447
0.5068 Remote Similarity NPC479054

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC507811 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
0.6346 Remote Similarity NPD1552 Clinical (unspecified phase)
0.5769 Remote Similarity NPD1549 Phase 2
0.5179 Remote Similarity NPD1550 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