Natural Product: NPC198826

Natural Product IDNPC198826
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 7-O-Methylscutellarein
IUPAC Name 5,6-dihydroxy-2-(4-hydroxyphenyl)-7-methoxychromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3740428
PubChem CID 3084390
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 UWARRXZVZDFPQU-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H12O6/c1-21-13-7-12-14(16(20)15(13)19)10(18)6-11(22-12)8-2-4-9(17)5-3-8/h2-7,17,19-20H,1H3
SMILES COc1cc2oc(cc(=O)c2c(c1O)O)c1ccc(cc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.06 Volume:   291.273
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Van der Waals volume.
Dense:   1.03 LogP:   2.386
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.252
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.096
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   100.13
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.629 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.326 Fsp3:   0.062
MCE-18:   18.0
?
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:   1
Colloidal aggregators:   0.617 Fluc inhibitor:   0.983
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.942
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.671
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.525 Promiscuous compounds:   0.928

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.037 MDCK Permeability:   -4.783
Pgp-inhibitor:   0.08 Pgp-substrate:   0.105
PAMPA:   0.733
?
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):   0.059
20% Bioavailability (F20%):   0.64 30% Bioavailability (F30%):   0.806
50% Bioavailability (F50%):   0.989

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.007 MRP1:   0.948
Plasma Protein Binding (PPB):   96.65% Volume Distribution (VD):   -0.47
Fu: 2.895%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.989
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.972
BSEP inhibitor:   0.657

ADMET: Metabolism

CYP1A2-inhibitor:   0.006 CYP1A2-substrate:   0.033
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.191 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.991 CYP2D6-substrate:   0.983
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.027
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.995
HLM stability:   0.208
?
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):  8.754 Half-life (T1/2):  1.493

ADMET: Toxicity

hERG Blockers:  0.104 hERG Blockers (10um):  0.517
Human Hepatotoxicity (H-HT):  0.406 Drug-induced Liver Injury (DILI):  0.728
AMES Toxicity:  0.528 Rat Oral Acute Toxicity:  0.435
Maximum Recommended Daily Dose:  0.733 Skin Sensitization:  0.718
Carcinogencity:  0.712 Eye Corrosion:  0.299
Eye Irritation:  0.992 Respiratory Toxicity:  0.686
Drug-induced Neurotoxicity:  0.117 Ototoxicity:  0.136
Hematotoxicity:  0.11 Drug-induced Nephrotoxicity:  0.057
Genotoxicity:  0.927 RPMI-8226 Immunitoxicity:  0.047
A549 Cytotoxicity:  0.317 Hek293 Cytotoxicity:  0.657
BCF:   1.041
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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:   3.541
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.395
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.998
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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
NPO9153 Sorbaria sorbifolia Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9153 Sorbaria sorbifolia Species Rosaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9153 Sorbaria sorbifolia Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9153 Sorbaria sorbifolia Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO9153 Sorbaria sorbifolia Species Rosaceae 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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 82.3 % PMID[26523667]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 56.19 % PMID[26523667]
NPT2535 Tissue Plasma Oryctolagus cuniculus PT = 6.55 s PMID[26523667]
NPT2535 Tissue Plasma Oryctolagus cuniculus TT = 25.48 s PMID[26523667]
NPT2535 Tissue Plasma Oryctolagus cuniculus APTT = 34.49 s PMID[26523667]
NPT2535 Tissue Plasma Oryctolagus cuniculus Activity = 5.74 g/L PMID[26523667]

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 NPC198826 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
0.8235 Intermediate Similarity NPC162313
0.82 Intermediate Similarity NPC275722
0.8039 Intermediate Similarity NPC57030
0.7407 Intermediate Similarity NPC212678
0.7273 Intermediate Similarity NPC283600
0.7037 Intermediate Similarity NPC234133
0.7037 Intermediate Similarity NPC120163
0.6909 Remote Similarity NPC78913
0.6897 Remote Similarity NPC485299
0.6852 Remote Similarity NPC71334
0.6545 Remote Similarity NPC241498
0.6324 Remote Similarity NPC146792
0.6197 Remote Similarity NPC43211
0.614 Remote Similarity NPC250266
0.6111 Remote Similarity NPC130230
0.6071 Remote Similarity NPC607196
0.6034 Remote Similarity NPC305663
0.5965 Remote Similarity NPC301323
0.5965 Remote Similarity NPC275836
0.5965 Remote Similarity NPC47815
0.5862 Remote Similarity NPC231018
0.5833 Remote Similarity NPC18607
0.5763 Remote Similarity NPC108406
0.5763 Remote Similarity NPC159275
0.5763 Remote Similarity NPC25270
0.5738 Remote Similarity NPC47781
0.5738 Remote Similarity NPC137062
0.569 Remote Similarity NPC43243
0.569 Remote Similarity NPC127447
0.569 Remote Similarity NPC239128
0.569 Remote Similarity NPC29353
0.5636 Remote Similarity NPC50898
0.5625 Remote Similarity NPC476185
0.5593 Remote Similarity NPC184136
0.5593 Remote Similarity NPC18260
0.5593 Remote Similarity NPC145379
0.5574 Remote Similarity NPC124784
0.5574 Remote Similarity NPC128863
0.5538 Remote Similarity NPC265932
0.5517 Remote Similarity NPC226973
0.5507 Remote Similarity NPC600972
0.5507 Remote Similarity NPC601984
0.5507 Remote Similarity NPC603508
0.5484 Remote Similarity NPC183950
0.5484 Remote Similarity NPC610914
0.5455 Remote Similarity NPC216318
0.5455 Remote Similarity NPC61871
0.5429 Remote Similarity NPC600396
0.541 Remote Similarity NPC300943
0.541 Remote Similarity NPC83508
0.5385 Remote Similarity NPC110969
0.5352 Remote Similarity NPC159707
0.5352 Remote Similarity NPC194593
0.5352 Remote Similarity NPC272064
0.5342 Remote Similarity NPC58716
0.5333 Remote Similarity NPC100887
0.5333 Remote Similarity NPC48479
0.5333 Remote Similarity NPC231772
0.5333 Remote Similarity NPC22519
0.5333 Remote Similarity NPC276409
0.5333 Remote Similarity NPC604462
0.5323 Remote Similarity NPC160951
0.5323 Remote Similarity NPC223579
0.5278 Remote Similarity NPC45618
0.5254 Remote Similarity NPC293183
0.5254 Remote Similarity NPC75279
0.5205 Remote Similarity NPC93337
0.5205 Remote Similarity NPC205026
0.52 Remote Similarity NPC237435
0.5179 Remote Similarity NPC172262
0.5167 Remote Similarity NPC156222
0.5161 Remote Similarity NPC69394
0.5161 Remote Similarity NPC20830
0.5135 Remote Similarity NPC10807
0.5135 Remote Similarity NPC161881
0.5135 Remote Similarity NPC105025
0.5135 Remote Similarity NPC265624
0.5088 Remote Similarity NPC22783
0.5088 Remote Similarity NPC12367
0.5082 Remote Similarity NPC33265
0.5082 Remote Similarity NPC143799
0.5082 Remote Similarity NPC146679
0.5082 Remote Similarity NPC120464
0.5082 Remote Similarity NPC266597
0.5082 Remote Similarity NPC101830
0.5082 Remote Similarity NPC604085
0.5079 Remote Similarity NPC195202
0.5079 Remote Similarity NPC52005
0.5079 Remote Similarity NPC115323

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC198826 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
0.52 Remote Similarity NPD4338 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