Natural Product: NPC164272

Natural Product IDNPC164272
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 GMGRYHOHJJROMP-BODNZJIQSA-N
IUPAC Name n.a.
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: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 GMGRYHOHJJROMP-BODNZJIQSA-N
Standard InCHI InChI=1S/C26H30O7/c1-14(2)6-5-7-15(3)8-9-17-18(27)12-23-24(25(17)31)19(28)13-22(33-23)16-10-20(29)26(32-4)21(30)11-16/h6,8,10-12,22,27,29-31H,5,7,9,13H2,1-4H3/b15-8+/t22-/m0/s1
SMILES CC(=CCC/C(=C/Cc1c(cc2c(C(=O)C[C@@H](c3cc(c(c(c3)O)OC)O)O2)c1O)O)/C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   454.2 Volume:   470.386
?
Van der Waals volume.
Dense:   0.966 LogP:   5.919
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.964
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.448
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   20.0
TPSA:   116.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.411 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.646 Fsp3:   0.346
MCE-18:   68.514
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.906 Fluc inhibitor:   0.73
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.562
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.833
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.362 Promiscuous compounds:   0.134

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.012 MDCK Permeability:   -4.747
Pgp-inhibitor:   0.977 Pgp-substrate:   0.0
PAMPA:   0.047
?
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%):   0.144 30% Bioavailability (F30%):   0.669
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.922
Plasma Protein Binding (PPB):   96.931% Volume Distribution (VD):   -0.055
Fu: 2.753%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.228
BSEP inhibitor:   0.774

ADMET: Metabolism

CYP1A2-inhibitor:   0.74 CYP1A2-substrate:   0.962
CYP2C19-inhibitor:   0.106 CYP2C19-substrate:   0.991
CYP2C9-inhibitor:   0.232 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.217
CYP3A4-inhibitor:   0.951 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.992
?
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):  3.749 Half-life (T1/2):  1.443

ADMET: Toxicity

hERG Blockers:  0.059 hERG Blockers (10um):  0.546
Human Hepatotoxicity (H-HT):  0.847 Drug-induced Liver Injury (DILI):  0.934
AMES Toxicity:  0.371 Rat Oral Acute Toxicity:  0.809
Maximum Recommended Daily Dose:  0.713 Skin Sensitization:  0.99
Carcinogencity:  0.303 Eye Corrosion:  0.001
Eye Irritation:  0.925 Respiratory Toxicity:  0.994
Drug-induced Neurotoxicity:  0.441 Ototoxicity:  0.558
Hematotoxicity:  0.296 Drug-induced Nephrotoxicity:  0.813
Genotoxicity:  0.978 RPMI-8226 Immunitoxicity:  0.385
A549 Cytotoxicity:  0.939 Hek293 Cytotoxicity:  0.64
BCF:   2.132
?
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:   4.787
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.437
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.804
?
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
NPT279 Individual protein Leukocyte elastase Homo sapiens IC50 = 3300.0 nM PMID[28968119]
NPT279 Individual protein Leukocyte elastase Homo sapiens Ki = 3200.0 nM PMID[28968119]

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 NPC164272 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
1.0 High Similarity NPC470327
0.8507 High Similarity NPC278778
0.8333 Intermediate Similarity NPC64915
0.8261 Intermediate Similarity NPC472626
0.8182 Intermediate Similarity NPC290133
0.7941 Intermediate Similarity NPC470328
0.7941 Intermediate Similarity NPC209614
0.7857 Intermediate Similarity NPC488554
0.7794 Intermediate Similarity NPC213896
0.7746 Intermediate Similarity NPC45849
0.7746 Intermediate Similarity NPC195796
0.7714 Intermediate Similarity NPC226025
0.7647 Intermediate Similarity NPC228504
0.7465 Intermediate Similarity NPC298692
0.7324 Intermediate Similarity NPC185276
0.7222 Intermediate Similarity NPC470326
0.68 Remote Similarity NPC488557
0.6579 Remote Similarity NPC210459
0.6389 Remote Similarity NPC35038
0.6364 Remote Similarity NPC282009
0.6324 Remote Similarity NPC1089
0.6316 Remote Similarity NPC488558
0.6234 Remote Similarity NPC472630
0.6203 Remote Similarity NPC488555
0.6203 Remote Similarity NPC484418
0.6184 Remote Similarity NPC261063
0.6154 Remote Similarity NPC472631
0.6125 Remote Similarity NPC474055
0.6104 Remote Similarity NPC321779
0.6076 Remote Similarity NPC472598
0.6056 Remote Similarity NPC125855
0.6053 Remote Similarity NPC488556
0.6049 Remote Similarity NPC472634
0.6027 Remote Similarity NPC223787
0.6026 Remote Similarity NPC472628
0.5976 Remote Similarity NPC321399
0.5974 Remote Similarity NPC472627
0.5974 Remote Similarity NPC58805
0.5921 Remote Similarity NPC472629
0.5921 Remote Similarity NPC279650
0.5875 Remote Similarity NPC27337
0.5802 Remote Similarity NPC287328
0.5769 Remote Similarity NPC22192
0.5641 Remote Similarity NPC262039
0.5616 Remote Similarity NPC223500
0.5616 Remote Similarity NPC166689
0.5526 Remote Similarity NPC24136
0.5526 Remote Similarity NPC477242
0.5479 Remote Similarity NPC480990
0.5385 Remote Similarity NPC96408
0.5385 Remote Similarity NPC610511
0.5375 Remote Similarity NPC299436
0.5309 Remote Similarity NPC201800
0.5294 Remote Similarity NPC293319
0.5294 Remote Similarity NPC480993
0.5122 Remote Similarity NPC67396
0.5063 Remote Similarity NPC166934
0.5062 Remote Similarity NPC267375

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC164272 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