Natural Product: NPC418074

Natural Product IDNPC418074
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 WURBFLDFSFBTLW-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 8651
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000253] Stilbenes

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 WURBFLDFSFBTLW-UHFFFAOYSA-N
Standard InCHI InChI=1S/C14H10O2/c15-13(11-7-3-1-4-8-11)14(16)12-9-5-2-6-10-12/h1-10H
SMILES c1ccc(cc1)C(=O)C(=O)c1ccccc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   210.07 Volume:   230.076
?
Van der Waals volume.
Dense:   0.913 LogP:   3.45
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.363
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.051
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   14.0
TPSA:   34.14
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.576 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.364 Fsp3:   0.0
MCE-18:   10.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   1
Colloidal aggregators:   0.125 Fluc inhibitor:   0.464
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.018
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.039
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   1.0 Promiscuous compounds:   0.946

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.261 MDCK Permeability:   -4.61
Pgp-inhibitor:   1.0 Pgp-substrate:   0.014
PAMPA:   0.144
?
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):   0.016
20% Bioavailability (F20%):   0.003 30% Bioavailability (F30%):   0.335
50% Bioavailability (F50%):   0.547

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.304 MRP1:   0.207
Plasma Protein Binding (PPB):   94.061% Volume Distribution (VD):   -0.19
Fu: 7.719%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.983
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.395
BSEP inhibitor:   0.96

ADMET: Metabolism

CYP1A2-inhibitor:   0.004 CYP1A2-substrate:   0.5
CYP2C19-inhibitor:   0.027 CYP2C19-substrate:   0.73
CYP2C9-inhibitor:   0.005 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.124
CYP3A4-inhibitor:   0.02 CYP3A4-substrate:   0.017
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.483
HLM stability:   0.467
?
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):  6.712 Half-life (T1/2):  1.299

ADMET: Toxicity

hERG Blockers:  0.185 hERG Blockers (10um):  0.526
Human Hepatotoxicity (H-HT):  0.561 Drug-induced Liver Injury (DILI):  0.6
AMES Toxicity:  0.369 Rat Oral Acute Toxicity:  0.252
Maximum Recommended Daily Dose:  0.401 Skin Sensitization:  0.692
Carcinogencity:  0.361 Eye Corrosion:  0.225
Eye Irritation:  0.985 Respiratory Toxicity:  0.68
Drug-induced Neurotoxicity:  0.712 Ototoxicity:  0.198
Hematotoxicity:  0.327 Drug-induced Nephrotoxicity:  0.506
Genotoxicity:  0.142 RPMI-8226 Immunitoxicity:  0.03
A549 Cytotoxicity:  0.099 Hek293 Cytotoxicity:  0.233
BCF:   1.289
?
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:   4.488
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.427
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.12
?
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
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[ 17014425]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. DOI[10.1002/bab.1236]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.indcrop.2010.09.006]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. root n.a. PMID[11374966]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[16038550]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[17583950]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[18855446]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[20455578]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[21775156]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[23286284]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[24108414]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[27569393]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[29185738]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[30351923]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. root n.a. PMID[3655791]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota roots n.a. n.a. PMID[9834151]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO5743 Salvia miltiorrhiza 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
NPT203 Individual protein Carboxylesterase 2 Homo sapiens Ki = 14.7 nM PMID[16107154]
NPT166 Individual protein Acyl coenzyme A:cholesterol acyltransferase Homo sapiens Ki = 45.1 nM PMID[16107154]
NPT166 Individual protein Acyl coenzyme A:cholesterol acyltransferase Homo sapiens Ki = 103.0 nM PMID[16107154]
NPT204 Individual protein Acetylcholinesterase Homo sapiens Ki > 100000.0 nM PMID[16107154]
NPT203 Individual protein Carboxylesterase 2 Homo sapiens Ki = 14.7 nM PMID[15828829]
NPT166 Individual protein Acyl coenzyme A:cholesterol acyltransferase Homo sapiens Ki = 6.9 nM PMID[15828829]
NPT2610 Individual protein Acyl coenzyme A:cholesterol acyltransferase Oryctolagus cuniculus Ki = 103.0 nM PMID[15828829]
NPT2610 Individual protein Acyl coenzyme A:cholesterol acyltransferase Oryctolagus cuniculus Ki = 13.6 nM PMID[15828829]
NPT2610 Individual protein Acyl coenzyme A:cholesterol acyltransferase Oryctolagus cuniculus Ki = 185.0 nM PMID[15828829]
NPT166 Individual protein Acyl coenzyme A:cholesterol acyltransferase Homo sapiens Ki = 45.1 nM PMID[15828829]
NPT204 Individual protein Acetylcholinesterase Homo sapiens Ki > 100000.0 nM PMID[15828829]
NPT203 Individual protein Carboxylesterase 2 Homo sapiens Ki = 24.0 nM PMID[15828829]
NPT203 Individual protein Carboxylesterase 2 Homo sapiens Ki = 175.0 nM PMID[15828829]
NPT203 Individual protein Carboxylesterase 2 Homo sapiens Ki = 15.1 nM PMID[17399985]
NPT166 Individual protein Acyl coenzyme A:cholesterol acyltransferase Homo sapiens Ki = 45.1 nM PMID[17399985]
NPT204 Individual protein Acetylcholinesterase Homo sapiens Ki > 100000.0 nM PMID[17399985]
NPT204 Individual protein Acetylcholinesterase Homo sapiens Ki > 100000.0 nM PMID[17941623]
NPT166 Individual protein Acyl coenzyme A:cholesterol acyltransferase Homo sapiens IC50 = 27.0 nM PMID[18023188]
NPT166 Individual protein Acyl coenzyme A:cholesterol acyltransferase Homo sapiens IC50 = 43.0 nM PMID[18023188]
NPT203 Individual protein Carboxylesterase 2 Homo sapiens IC50 = 38.0 nM PMID[18023188]
NPT203 Individual protein Carboxylesterase 2 Homo sapiens IC50 = 44.0 nM PMID[18023188]
NPT1418 Individual protein Anandamide amidohydrolase Homo sapiens IC50 > 40000.0 nM PMID[18023188]
NPT166 Individual protein Acyl coenzyme A:cholesterol acyltransferase Homo sapiens Ki = 44.67 nM PMID[19062296]
NPT166 Individual protein Acyl coenzyme A:cholesterol acyltransferase Homo sapiens Ki = 15.0 nM PMID[21733699]
NPT203 Individual protein Carboxylesterase 2 Homo sapiens Ki = 45.0 nM PMID[21733699]
NPT2610 Individual protein Acyl coenzyme A:cholesterol acyltransferase Oryctolagus cuniculus Ki = 103.0 nM PMID[21733699]
NPT204 Individual protein Acetylcholinesterase Homo sapiens Ki > 100000.0 nM PMID[21733699]
NPT203 Individual protein Carboxylesterase 2 Homo sapiens Inhibition < 8.0 % PMID[21733699]
NPT203 Individual protein Carboxylesterase 2 Homo sapiens Ki = 175.0 nM PMID[21733699]
NPT203 Individual protein Carboxylesterase 2 Homo sapiens Inhibition = 95.1 % PMID[21733699]
NPT203 Individual protein Carboxylesterase 2 Homo sapiens Inhibition = 83.8 % PMID[23286284]
NPT203 Individual protein Carboxylesterase 2 Homo sapiens Ki = 15.0 nM PMID[23286284]
NPT166 Individual protein Acyl coenzyme A:cholesterol acyltransferase Homo sapiens Ki = 45.0 nM PMID[23286284]
NPT204 Individual protein Acetylcholinesterase Homo sapiens IC50 > 100000.0 nM PMID[26827140]
NPT166 Individual protein Acyl coenzyme A:cholesterol acyltransferase Homo sapiens IC50 = 370.0 nM PMID[26827140]
NPT166 Individual protein Acyl coenzyme A:cholesterol acyltransferase Homo sapiens Activity = 85.0 % PMID[30351923]
NPT166 Individual protein Acyl coenzyme A:cholesterol acyltransferase Homo sapiens Activity = 5.0 % PMID[30351923]
NPT837 Individual protein Carboxylesterase Sus scrofa IC50 = 370.0 nM PMID[18023188]
NPT837 Individual protein Carboxylesterase Sus scrofa IC50 = 830.0 nM PMID[18023188]
NPT439 Individual protein Butyrylcholinesterase Homo sapiens Ki > 100000.0 nM PMID[15828829]
NPT439 Individual protein Butyrylcholinesterase Homo sapiens Ki > 100000.0 nM PMID[17399985]
NPT439 Individual protein Butyrylcholinesterase Homo sapiens Ki > 100000.0 nM PMID[17941623]
NPT439 Individual protein Butyrylcholinesterase Homo sapiens Ki > 100000.0 nM PMID[21733699]
NPT439 Individual protein Butyrylcholinesterase Homo sapiens IC50 > 100000.0 nM PMID[26827140]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT933 Cell line U373 MG Homo sapiens FC = 6.0 n.a. PMID[21733699]
NPT933 Cell line U373 MG Homo sapiens FC = 5.4 n.a. PMID[23286284]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 100000.0 nM PMID[21733699]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 22900.0 nM PMID[21733699]
NPT2 Others Unspecified n.a. Ki = 103.0 nM PMID[17399985]
NPT2 Others Unspecified n.a. IC50 = 19.0 nM PMID[18023188]
NPT2 Others Unspecified n.a. IC50 = 29.0 nM PMID[18023188]
NPT2 Others Unspecified n.a. Ki = 14.79 nM PMID[19062296]
NPT2 Others Unspecified n.a. Ki = 102.33 nM PMID[19062296]
NPT2 Others Unspecified n.a. Activity = 98.0 % PMID[30351923]

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
- Mus musculus LD50 > 3000.0 mg/kg ToxVal

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 NPC418074 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
0.6316 Remote Similarity NPC2785
0.619 Remote Similarity NPC73978
0.5909 Remote Similarity NPC285470
0.5909 Remote Similarity NPC245966
0.5909 Remote Similarity NPC190567
0.5909 Remote Similarity NPC273758
0.5909 Remote Similarity NPC300205
0.5652 Remote Similarity NPC324624
0.5417 Remote Similarity NPC246757
0.5417 Remote Similarity NPC291070
0.5417 Remote Similarity NPC36342
0.52 Remote Similarity NPC164086

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC418074 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