Natural Product: NPC488084

Natural Product IDNPC488084
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 XQRSFBPLYOVSRU-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 12591025
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002593] 8-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 XQRSFBPLYOVSRU-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O6/c1-21-15-13-11(19)9-12(10-7-5-4-6-8-10)24-16(13)18(23-3)17(22-2)14(15)20/h4-9,20H,1-3H3
SMILES COc1c2c(=O)cc(c3ccccc3)oc2c(c(c1O)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   328.09 Volume:   325.865
?
Van der Waals volume.
Dense:   1.007 LogP:   2.681
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.596
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.669
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   78.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.792 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.396 Fsp3:   0.167
MCE-18:   18.0
?
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:   0.16 Fluc inhibitor:   0.402
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.765
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.549
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.3 Promiscuous compounds:   0.477

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.956 MDCK Permeability:   -4.749
Pgp-inhibitor:   0.983 Pgp-substrate:   0.057
PAMPA:   0.081
?
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):   0.002
20% Bioavailability (F20%):   0.037 30% Bioavailability (F30%):   0.21
50% Bioavailability (F50%):   0.749

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.697 MRP1:   0.979
Plasma Protein Binding (PPB):   98.822% Volume Distribution (VD):   -0.306
Fu: 0.691%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.943
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.934
BSEP inhibitor:   0.992

ADMET: Metabolism

CYP1A2-inhibitor:   0.673 CYP1A2-substrate:   0.874
CYP2C19-inhibitor:   0.407 CYP2C19-substrate:   0.333
CYP2C9-inhibitor:   0.448 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.863 CYP2D6-substrate:   0.099
CYP3A4-inhibitor:   0.835 CYP3A4-substrate:   0.758
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.966
HLM stability:   0.601
?
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):  5.862 Half-life (T1/2):  1.357

ADMET: Toxicity

hERG Blockers:  0.146 hERG Blockers (10um):  0.574
Human Hepatotoxicity (H-HT):  0.485 Drug-induced Liver Injury (DILI):  0.856
AMES Toxicity:  0.344 Rat Oral Acute Toxicity:  0.431
Maximum Recommended Daily Dose:  0.464 Skin Sensitization:  0.688
Carcinogencity:  0.764 Eye Corrosion:  0.22
Eye Irritation:  0.9 Respiratory Toxicity:  0.66
Drug-induced Neurotoxicity:  0.458 Ototoxicity:  0.156
Hematotoxicity:  0.351 Drug-induced Nephrotoxicity:  0.167
Genotoxicity:  0.243 RPMI-8226 Immunitoxicity:  0.085
A549 Cytotoxicity:  0.2 Hek293 Cytotoxicity:  0.415
BCF:   1.334
?
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:   3.767
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.132
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.29
?
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
NPO21355 Elsholtzia ciliata Species Lamiaceae Eukaryota Aerial Parts n.a. n.a. PMID[32991171]
NPO21355 Elsholtzia ciliata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21355 Elsholtzia ciliata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21355 Elsholtzia ciliata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21355 Elsholtzia ciliata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21355 Elsholtzia ciliata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO21355 Elsholtzia ciliata Species Lamiaceae 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
NPT68 Individual protein Aldose reductase Rattus norvegicus IC50 = 288403.15 nM PMID[18585047]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT804 Cell line HT-22 Mus musculus EC50 = 43600.0 nM PMID[32991171]

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 NPC488084 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
0.6182 Remote Similarity NPC602963
0.6071 Remote Similarity NPC306821
0.6071 Remote Similarity NPC609062
0.5893 Remote Similarity NPC226973
0.5893 Remote Similarity NPC131624
0.5789 Remote Similarity NPC194281
0.5593 Remote Similarity NPC217186
0.5536 Remote Similarity NPC602026
0.5517 Remote Similarity NPC71334
0.5517 Remote Similarity NPC138360
0.5517 Remote Similarity NPC239128
0.5455 Remote Similarity NPC41721
0.5424 Remote Similarity NPC22519
0.5357 Remote Similarity NPC40818
0.5345 Remote Similarity NPC293183
0.5345 Remote Similarity NPC601286
0.5333 Remote Similarity NPC50715
0.5263 Remote Similarity NPC284424
0.5263 Remote Similarity NPC278556
0.5263 Remote Similarity NPC106461
0.5254 Remote Similarity NPC275722
0.5254 Remote Similarity NPC127447
0.5254 Remote Similarity NPC187498
0.5246 Remote Similarity NPC167815
0.5172 Remote Similarity NPC129680
0.5167 Remote Similarity NPC53181
0.5167 Remote Similarity NPC18260
0.5167 Remote Similarity NPC176775
0.5167 Remote Similarity NPC231018

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC488084 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