Natural Product: NPC144281

Natural Product IDNPC144281
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 WGVFVBIJKULVHA-QHHAFSJGSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5372365
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003467] Linear 1,3-diarylpropanoids
        • [CHEMONTID:0001630] Chalcones and dihydrochalcones
          • [CHEMONTID:0003472] 2'-Hydroxychalcones

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 WGVFVBIJKULVHA-QHHAFSJGSA-N
Standard InCHI InChI=1S/C16H14O5/c1-21-16-7-3-10(8-15(16)20)2-6-13(18)12-5-4-11(17)9-14(12)19/h2-9,17,19-20H,1H3/b6-2+
SMILES COc1ccc(/C=C/C(=O)c2ccc(cc2O)O)cc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   286.08 Volume:   291.039
?
Van der Waals volume.
Dense:   0.983 LogP:   2.503
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.609
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.381
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   14.0
TPSA:   86.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.594 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.154 Fsp3:   0.062
MCE-18:   13.0
?
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:   0.872 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.549
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.796
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.833 Promiscuous compounds:   0.698

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.999 MDCK Permeability:   -4.85
Pgp-inhibitor:   0.222 Pgp-substrate:   0.032
PAMPA:   0.085
?
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):   0.01
20% Bioavailability (F20%):   0.396 30% Bioavailability (F30%):   0.82
50% Bioavailability (F50%):   0.978

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.009 MRP1:   0.152
Plasma Protein Binding (PPB):   97.022% Volume Distribution (VD):   -0.57
Fu: 2.644%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.995
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.748
BSEP inhibitor:   0.482

ADMET: Metabolism

CYP1A2-inhibitor:   0.325 CYP1A2-substrate:   0.992
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.086
CYP2C9-inhibitor:   0.998 CYP2C9-substrate:   0.994
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.223
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.082
?
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):  4.303 Half-life (T1/2):  1.735

ADMET: Toxicity

hERG Blockers:  0.132 hERG Blockers (10um):  0.484
Human Hepatotoxicity (H-HT):  0.428 Drug-induced Liver Injury (DILI):  0.256
AMES Toxicity:  0.407 Rat Oral Acute Toxicity:  0.143
Maximum Recommended Daily Dose:  0.68 Skin Sensitization:  0.843
Carcinogencity:  0.336 Eye Corrosion:  0.155
Eye Irritation:  0.995 Respiratory Toxicity:  0.691
Drug-induced Neurotoxicity:  0.288 Ototoxicity:  0.126
Hematotoxicity:  0.071 Drug-induced Nephrotoxicity:  0.233
Genotoxicity:  0.471 RPMI-8226 Immunitoxicity:  0.1
A549 Cytotoxicity:  0.258 Hek293 Cytotoxicity:  0.724
BCF:   1.201
?
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:   4.101
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.92
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.59
?
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

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 = 35200.0 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 NPC144281 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
0.7609 Intermediate Similarity NPC262359
0.7347 Intermediate Similarity NPC254659
0.6957 Remote Similarity NPC26697
0.6809 Remote Similarity NPC13238
0.6667 Remote Similarity NPC19174
0.6667 Remote Similarity NPC115159
0.6383 Remote Similarity NPC297186
0.6222 Remote Similarity NPC267552
0.6071 Remote Similarity NPC131039
0.5882 Remote Similarity NPC205468
0.5862 Remote Similarity NPC185526
0.5833 Remote Similarity NPC190487
0.5769 Remote Similarity NPC284556
0.5769 Remote Similarity NPC605344
0.5714 Remote Similarity NPC224273
0.56 Remote Similarity NPC139813
0.5593 Remote Similarity NPC235239
0.5455 Remote Similarity NPC190043
0.537 Remote Similarity NPC129132
0.5345 Remote Similarity NPC65005
0.5333 Remote Similarity NPC11056
0.5283 Remote Similarity NPC165389
0.5263 Remote Similarity NPC169250
0.5263 Remote Similarity NPC44960
0.5238 Remote Similarity NPC484050
0.5185 Remote Similarity NPC142165
0.5185 Remote Similarity NPC66905
0.5179 Remote Similarity NPC472365
0.5156 Remote Similarity NPC608873
0.5156 Remote Similarity NPC609853
0.5147 Remote Similarity NPC488085
0.5102 Remote Similarity NPC232084
0.5102 Remote Similarity NPC247364
0.5098 Remote Similarity NPC122793
0.5094 Remote Similarity NPC64359
0.5091 Remote Similarity NPC301178
0.5091 Remote Similarity NPC56031

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC144281 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