Natural Product: NPC472636

Natural Product IDNPC472636
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 WTGUNSGYPQJOLT-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3581359
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003646] 6-prenylated flavans
            • [CHEMONTID:0003507] 6-prenylated flavanones

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 WTGUNSGYPQJOLT-UHFFFAOYSA-N
Standard InCHI InChI=1S/C25H28O6/c1-14(2)5-4-10-25(3,29)22-11-17-20(31-22)13-21-23(24(17)28)18(27)12-19(30-21)15-6-8-16(26)9-7-15/h5-9,13,19,22,26,28-29H,4,10-12H2,1-3H3
SMILES CC(=CCCC(C1Cc2c(O1)cc1c(c2O)C(=O)CC(O1)c1ccc(cc1)O)(O)C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   424.19 Volume:   438.38
?
Van der Waals volume.
Dense:   0.968 LogP:   4.635
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.69
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.972
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   23.0
TPSA:   96.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.607 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.03 Fsp3:   0.4
MCE-18:   83.943
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.523 Fluc inhibitor:   0.335
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.31
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.533
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.105 Promiscuous compounds:   0.023

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.919 MDCK Permeability:   -4.752
Pgp-inhibitor:   0.991 Pgp-substrate:   0.052
PAMPA:   0.751
?
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%):   0.018 30% Bioavailability (F30%):   0.77
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.936
Plasma Protein Binding (PPB):   96.135% Volume Distribution (VD):   0.263
Fu: 4.044%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.992
BSEP inhibitor:   0.995

ADMET: Metabolism

CYP1A2-inhibitor:   0.036 CYP1A2-substrate:   0.958
CYP2C19-inhibitor:   0.832 CYP2C19-substrate:   0.488
CYP2C9-inhibitor:   0.437 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.125 CYP2D6-substrate:   0.772
CYP3A4-inhibitor:   0.002 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.147
HLM stability:   0.981
?
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):  7.07 Half-life (T1/2):  1.065

ADMET: Toxicity

hERG Blockers:  0.249 hERG Blockers (10um):  0.632
Human Hepatotoxicity (H-HT):  0.747 Drug-induced Liver Injury (DILI):  0.196
AMES Toxicity:  0.506 Rat Oral Acute Toxicity:  0.418
Maximum Recommended Daily Dose:  0.613 Skin Sensitization:  0.858
Carcinogencity:  0.649 Eye Corrosion:  0.0
Eye Irritation:  0.786 Respiratory Toxicity:  0.731
Drug-induced Neurotoxicity:  0.214 Ototoxicity:  0.606
Hematotoxicity:  0.155 Drug-induced Nephrotoxicity:  0.576
Genotoxicity:  0.473 RPMI-8226 Immunitoxicity:  0.085
A549 Cytotoxicity:  0.351 Hek293 Cytotoxicity:  0.693
BCF:   1.612
?
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:   4.319
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.823
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.176
?
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
NPO22079 Paulownia tomentosa Species Paulowniaceae Eukaryota fruits n.a. n.a. PMID[17625893]
NPO22079 Paulownia tomentosa Species Paulowniaceae Eukaryota Fruits n.a. n.a. PMID[18293924]
NPO22079 Paulownia tomentosa Species Paulowniaceae Eukaryota n.a. n.a. n.a. PMID[20192247]
NPO22079 Paulownia tomentosa Species Paulowniaceae Eukaryota n.a. fruit n.a. PMID[21319773]
NPO22079 Paulownia tomentosa Species Paulowniaceae Eukaryota fruits n.a. n.a. PMID[22445674]
NPO22079 Paulownia tomentosa Species Paulowniaceae Eukaryota fruits n.a. n.a. PMID[23623680]
NPO22079 Paulownia tomentosa Species Paulowniaceae Eukaryota fruits n.a. n.a. PMID[25735399]
NPO22079 Paulownia tomentosa Species Paulowniaceae Eukaryota Fruits n.a. n.a. PMID[28322565]
NPO22079 Paulownia tomentosa Species Paulowniaceae Eukaryota Fruits n.a. n.a. PMID[28968119]
NPO22079 Paulownia tomentosa Species Paulowniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22079 Paulownia tomentosa Species Paulowniaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22079 Paulownia tomentosa Species Paulowniaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22079 Paulownia tomentosa Species Paulowniaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO22079 Paulownia tomentosa Species Paulowniaceae 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
NPT1970 Cell line THP-1 Homo sapiens IC50 > 10000.0 nM PMID[19223615]

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 NPC472636 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
0.8143 Intermediate Similarity NPC472624
0.6849 Remote Similarity NPC479216
0.6471 Remote Similarity NPC69674
0.6056 Remote Similarity NPC486094
0.5714 Remote Similarity NPC488553
0.5634 Remote Similarity NPC472580
0.5513 Remote Similarity NPC472629
0.5385 Remote Similarity NPC228504
0.5238 Remote Similarity NPC472632
0.5072 Remote Similarity NPC329203
0.5072 Remote Similarity NPC222342
0.5068 Remote Similarity NPC169591
0.5068 Remote Similarity NPC298223
0.5068 Remote Similarity NPC604412
0.5067 Remote Similarity NPC470131
0.5067 Remote Similarity NPC470132
0.5062 Remote Similarity NPC488556

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC472636 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