Natural Product: NPC472629

Natural Product IDNPC472629
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 GPHIDEIQYPAQLK-BPARTEKVSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3581349
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 GPHIDEIQYPAQLK-BPARTEKVSA-N
Standard InCHI InChI=1S/C25H28O6/c1-14(2)5-4-6-15(3)19(27)11-18-20(28)12-23-24(25(18)30)21(29)13-22(31-23)16-7-9-17(26)10-8-16/h5,7-10,12,19,22,26-28,30H,3-4,6,11,13H2,1-2H3/t19?,22-/m0/s1
SMILES CC(=CCCC(=C)C(Cc1c(O)cc2c(c1O)C(=O)C[C@H](O2)c1ccc(cc1)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   424.19 Volume:   444.3
?
Van der Waals volume.
Dense:   0.955 LogP:   4.686
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.631
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.011
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   20.0
TPSA:   107.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.479 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.834 Fsp3:   0.32
MCE-18:   65.545
?
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:   0.755 Fluc inhibitor:   0.515
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.378
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.499
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.154 Promiscuous compounds:   0.011

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.955 MDCK Permeability:   -4.734
Pgp-inhibitor:   0.917 Pgp-substrate:   0.015
PAMPA:   0.825
?
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):   0.001
20% Bioavailability (F20%):   0.0 30% Bioavailability (F30%):   0.81
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.981
Plasma Protein Binding (PPB):   96.726% Volume Distribution (VD):   0.258
Fu: 3.068%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.994
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.952
BSEP inhibitor:   0.99

ADMET: Metabolism

CYP1A2-inhibitor:   0.106 CYP1A2-substrate:   0.599
CYP2C19-inhibitor:   0.048 CYP2C19-substrate:   0.046
CYP2C9-inhibitor:   0.039 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.398 CYP2D6-substrate:   0.998
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.013
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.398
HLM stability:   0.996
?
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):  6.47 Half-life (T1/2):  1.23

ADMET: Toxicity

hERG Blockers:  0.053 hERG Blockers (10um):  0.482
Human Hepatotoxicity (H-HT):  0.603 Drug-induced Liver Injury (DILI):  0.06
AMES Toxicity:  0.34 Rat Oral Acute Toxicity:  0.188
Maximum Recommended Daily Dose:  0.531 Skin Sensitization:  0.871
Carcinogencity:  0.333 Eye Corrosion:  0.003
Eye Irritation:  0.983 Respiratory Toxicity:  0.365
Drug-induced Neurotoxicity:  0.618 Ototoxicity:  0.608
Hematotoxicity:  0.083 Drug-induced Nephrotoxicity:  0.567
Genotoxicity:  0.71 RPMI-8226 Immunitoxicity:  0.092
A549 Cytotoxicity:  0.237 Hek293 Cytotoxicity:  0.373
BCF:   1.764
?
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:   4.683
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.21
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.641
?
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 > 11400.0 nM PMID[23634786]

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 NPC472629 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
0.8 Intermediate Similarity NPC472598
0.75 Intermediate Similarity NPC228504
0.6901 Remote Similarity NPC213896
0.6528 Remote Similarity NPC479214
0.6486 Remote Similarity NPC472627
0.6351 Remote Similarity NPC488556
0.6316 Remote Similarity NPC472628
0.6301 Remote Similarity NPC290133
0.6267 Remote Similarity NPC185276
0.625 Remote Similarity NPC321399
0.6216 Remote Similarity NPC64915
0.6184 Remote Similarity NPC321779
0.6026 Remote Similarity NPC195796
0.5974 Remote Similarity NPC278778
0.5974 Remote Similarity NPC298692
0.5942 Remote Similarity NPC1089
0.5921 Remote Similarity NPC164272
0.5921 Remote Similarity NPC470327
0.5915 Remote Similarity NPC125855
0.5915 Remote Similarity NPC486094
0.5846 Remote Similarity NPC324386
0.5844 Remote Similarity NPC261063
0.5823 Remote Similarity NPC45849
0.5769 Remote Similarity NPC226025
0.5714 Remote Similarity NPC470328
0.5714 Remote Similarity NPC262039
0.5714 Remote Similarity NPC209614
0.5694 Remote Similarity NPC223500
0.5625 Remote Similarity NPC472626
0.56 Remote Similarity NPC35038
0.5513 Remote Similarity NPC479210
0.5513 Remote Similarity NPC472636
0.5479 Remote Similarity NPC484873
0.5443 Remote Similarity NPC22192
0.5432 Remote Similarity NPC210459
0.5422 Remote Similarity NPC474055
0.5417 Remote Similarity NPC69674
0.5385 Remote Similarity NPC475052
0.5342 Remote Similarity NPC321980
0.5342 Remote Similarity NPC220998
0.5325 Remote Similarity NPC166934
0.5309 Remote Similarity NPC488554
0.5303 Remote Similarity NPC32441
0.5303 Remote Similarity NPC79943
0.5278 Remote Similarity NPC39329
0.5278 Remote Similarity NPC51032
0.5263 Remote Similarity NPC470890
0.5233 Remote Similarity NPC472635
0.5205 Remote Similarity NPC265040
0.5176 Remote Similarity NPC472634
0.5147 Remote Similarity NPC300668
0.5135 Remote Similarity NPC470135
0.5072 Remote Similarity NPC321011
0.5072 Remote Similarity NPC294852
0.5072 Remote Similarity NPC469764
0.5072 Remote Similarity NPC188679
0.5062 Remote Similarity NPC479218
0.5062 Remote Similarity NPC58805
0.506 Remote Similarity NPC488557

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC472629 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
0.5303 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