Natural Product: NPC488558

Natural Product IDNPC488558
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 FKCQEGKMRGVTSE-FWAYRLMKSA-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:0002585] O-methylated flavonoids
          • [CHEMONTID:0002595] 3'-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 FKCQEGKMRGVTSE-FWAYRLMKSA-N
Standard InCHI InChI=1S/C27H34O8/c1-15(7-6-10-27(2,3)32)8-9-17-18(28)13-21-24(25(17)30)19(29)14-20(35-21)16-11-22(33-4)26(31)23(12-16)34-5/h8,11-13,20,28,30-32H,6-7,9-10,14H2,1-5H3/b15-8+/t20-/m0/s1
SMILES C/C(=CCc1c(cc2c(C(=O)C[C@@H](c3cc(c(c(c3)OC)O)OC)O2)c1O)O)/CCCC(C)(C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   486.23 Volume:   499.109
?
Van der Waals volume.
Dense:   0.974 LogP:   4.092
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.085
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.017
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   19.0
TPSA:   125.68
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.367 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.546 Fsp3:   0.444
MCE-18:   74.462
?
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:   0.453 Fluc inhibitor:   0.665
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.317
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.768
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.069 Promiscuous compounds:   0.171

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.149 MDCK Permeability:   -4.776
Pgp-inhibitor:   0.992 Pgp-substrate:   0.001
PAMPA:   0.001
?
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%):   0.012
50% Bioavailability (F50%):   0.942

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.634
Plasma Protein Binding (PPB):   97.356% Volume Distribution (VD):   -0.066
Fu: 2.191%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.993
BSEP inhibitor:   0.987

ADMET: Metabolism

CYP1A2-inhibitor:   0.952 CYP1A2-substrate:   0.993
CYP2C19-inhibitor:   0.994 CYP2C19-substrate:   0.607
CYP2C9-inhibitor:   0.617 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.01 CYP2D6-substrate:   0.94
CYP3A4-inhibitor:   0.354 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.991
?
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):  4.535 Half-life (T1/2):  1.342

ADMET: Toxicity

hERG Blockers:  0.058 hERG Blockers (10um):  0.419
Human Hepatotoxicity (H-HT):  0.91 Drug-induced Liver Injury (DILI):  0.821
AMES Toxicity:  0.557 Rat Oral Acute Toxicity:  0.635
Maximum Recommended Daily Dose:  0.819 Skin Sensitization:  0.955
Carcinogencity:  0.54 Eye Corrosion:  0.0
Eye Irritation:  0.62 Respiratory Toxicity:  0.981
Drug-induced Neurotoxicity:  0.323 Ototoxicity:  0.746
Hematotoxicity:  0.437 Drug-induced Nephrotoxicity:  0.933
Genotoxicity:  0.972 RPMI-8226 Immunitoxicity:  0.461
A549 Cytotoxicity:  0.779 Hek293 Cytotoxicity:  0.641
BCF:   1.361
?
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:   3.978
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.754
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.843
?
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 = 23300.0 nM PMID[28968119]
NPT279 Individual protein Leukocyte elastase Homo sapiens Ki = 19500.0 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 NPC488558 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
0.831 Intermediate Similarity NPC488555
0.831 Intermediate Similarity NPC484418
0.8143 Intermediate Similarity NPC472630
0.8028 Intermediate Similarity NPC488557
0.7971 Intermediate Similarity NPC470328
0.7971 Intermediate Similarity NPC209614
0.7778 Intermediate Similarity NPC472631
0.7714 Intermediate Similarity NPC488556
0.7606 Intermediate Similarity NPC261063
0.6623 Remote Similarity NPC45849
0.6623 Remote Similarity NPC195796
0.6582 Remote Similarity NPC474055
0.6538 Remote Similarity NPC27337
0.65 Remote Similarity NPC472634
0.6438 Remote Similarity NPC35038
0.64 Remote Similarity NPC64915
0.6364 Remote Similarity NPC226025
0.6364 Remote Similarity NPC278778
0.6316 Remote Similarity NPC164272
0.6316 Remote Similarity NPC470327
0.6282 Remote Similarity NPC488554
0.6234 Remote Similarity NPC472627
0.6203 Remote Similarity NPC472626
0.6076 Remote Similarity NPC472628
0.6053 Remote Similarity NPC290133
0.6053 Remote Similarity NPC228504
0.5974 Remote Similarity NPC213896
0.5949 Remote Similarity NPC321779
0.5915 Remote Similarity NPC1089
0.5867 Remote Similarity NPC223787
0.5823 Remote Similarity NPC185276
0.575 Remote Similarity NPC74924
0.575 Remote Similarity NPC298692
0.5732 Remote Similarity NPC484417
0.5676 Remote Similarity NPC125855
0.5432 Remote Similarity NPC471212
0.5357 Remote Similarity NPC472598
0.5294 Remote Similarity NPC287328
0.5263 Remote Similarity NPC223500
0.5263 Remote Similarity NPC166689
0.5238 Remote Similarity NPC210459
0.5238 Remote Similarity NPC24640
0.5233 Remote Similarity NPC471499
0.5059 Remote Similarity NPC282009

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC488558 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