Natural Product: NPC309770

Natural Product IDNPC309770
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 SHUOYHLZGOOKOL-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 13983739
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 SHUOYHLZGOOKOL-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O7/c1-22-11-7-10(19)12-14(21)17(23-2)15(24-16(12)13(11)20)8-3-5-9(18)6-4-8/h3-7,18-20H,1-2H3
SMILES COc1cc(c2c(=O)c(c(c3ccc(cc3)O)oc2c1O)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   330.07 Volume:   317.359
?
Van der Waals volume.
Dense:   1.04 LogP:   2.404
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.317
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.959
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   109.36
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.633 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.453 Fsp3:   0.118
MCE-18:   19.0
?
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:   0
Colloidal aggregators:   0.411 Fluc inhibitor:   0.469
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.87
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.492
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.372 Promiscuous compounds:   0.856

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.083 MDCK Permeability:   -4.779
Pgp-inhibitor:   0.633 Pgp-substrate:   0.123
PAMPA:   0.407
?
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):   0.025
20% Bioavailability (F20%):   0.069 30% Bioavailability (F30%):   0.197
50% Bioavailability (F50%):   0.972

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.02 MRP1:   0.856
Plasma Protein Binding (PPB):   98.005% Volume Distribution (VD):   -0.526
Fu: 1.515%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.484
OATP1B3 inhibitor:   0.942 BCRP inhibitor:   0.826
BSEP inhibitor:   0.972

ADMET: Metabolism

CYP1A2-inhibitor:   0.57 CYP1A2-substrate:   0.247
CYP2C19-inhibitor:   0.036 CYP2C19-substrate:   0.245
CYP2C9-inhibitor:   0.228 CYP2C9-substrate:   0.051
CYP2D6-inhibitor:   0.858 CYP2D6-substrate:   0.932
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   0.207
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.871
HLM stability:   0.872
?
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):  9.144 Half-life (T1/2):  1.549

ADMET: Toxicity

hERG Blockers:  0.075 hERG Blockers (10um):  0.455
Human Hepatotoxicity (H-HT):  0.446 Drug-induced Liver Injury (DILI):  0.822
AMES Toxicity:  0.483 Rat Oral Acute Toxicity:  0.47
Maximum Recommended Daily Dose:  0.548 Skin Sensitization:  0.611
Carcinogencity:  0.76 Eye Corrosion:  0.179
Eye Irritation:  0.976 Respiratory Toxicity:  0.633
Drug-induced Neurotoxicity:  0.101 Ototoxicity:  0.141
Hematotoxicity:  0.171 Drug-induced Nephrotoxicity:  0.072
Genotoxicity:  0.85 RPMI-8226 Immunitoxicity:  0.064
A549 Cytotoxicity:  0.193 Hek293 Cytotoxicity:  0.509
BCF:   1.168
?
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:   3.657
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.377
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.903
?
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
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota roots n.a. n.a. PMID[16989524]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. rhizome n.a. PMID[22863942]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota aerial parts n.a. n.a. PMID[24042007]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. PMID[38838926]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27222 Miconia cabucu Species Melastomataceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27011 Canthium schimperianum Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27423 Lepraria candelaris Species Stereocaulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27222 Miconia cabucu Species Melastomataceae 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 NPC309770 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
0.7273 Intermediate Similarity NPC605494
0.6727 Remote Similarity NPC146679
0.6727 Remote Similarity NPC605144
0.6316 Remote Similarity NPC32420
0.625 Remote Similarity NPC266960
0.625 Remote Similarity NPC103342
0.614 Remote Similarity NPC101830
0.5965 Remote Similarity NPC191459
0.5965 Remote Similarity NPC287979
0.5932 Remote Similarity NPC178343
0.5862 Remote Similarity NPC105242
0.5862 Remote Similarity NPC606763
0.5694 Remote Similarity NPC59534
0.569 Remote Similarity NPC187498
0.5593 Remote Similarity NPC188871
0.5517 Remote Similarity NPC136840
0.55 Remote Similarity NPC480465
0.55 Remote Similarity NPC607913
0.5484 Remote Similarity NPC78326
0.5484 Remote Similarity NPC152166
0.5424 Remote Similarity NPC189960
0.5424 Remote Similarity NPC90582
0.5424 Remote Similarity NPC103904
0.5424 Remote Similarity NPC262094
0.5333 Remote Similarity NPC286342
0.5333 Remote Similarity NPC32557
0.5254 Remote Similarity NPC607196
0.5238 Remote Similarity NPC279989
0.5167 Remote Similarity NPC184536
0.5161 Remote Similarity NPC270620
0.5161 Remote Similarity NPC253634
0.5135 Remote Similarity NPC349108
0.5082 Remote Similarity NPC59951
0.5082 Remote Similarity NPC143799
0.5082 Remote Similarity NPC234133
0.5082 Remote Similarity NPC176665
0.5082 Remote Similarity NPC163524
0.5079 Remote Similarity NPC603112
0.5075 Remote Similarity NPC306488

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC309770 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
NPD

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