Natural Product: NPC485345

Natural Product IDNPC485345
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CWRWTVQQOXCDEU-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 10879668
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0001831] Carbonyl compounds
          • [CHEMONTID:0000118] Ketones
            • [CHEMONTID:0001223] Alpha-diketones

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 CWRWTVQQOXCDEU-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H30O2/c1-3-5-7-9-11-13-15(17)16(18)14-12-10-8-6-4-2/h3-14H2,1-2H3
SMILES CCCCCCCC(=O)C(=O)CCCCCCC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   254.22 Volume:   297.6
?
Van der Waals volume.
Dense:   0.854 LogP:   5.384
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.843
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.991
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   13.0 Rigid Bonds:   2.0
TPSA:   34.14
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   0.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.348 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.98 Fsp3:   0.875
MCE-18:   0.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   1
Colloidal aggregators:   0.043 Fluc inhibitor:   0.116
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.003
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.001
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.997 Promiscuous compounds:   0.643

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.037 MDCK Permeability:   -4.814
Pgp-inhibitor:   0.033 Pgp-substrate:   0.045
PAMPA:   0.044
?
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):   0.104
20% Bioavailability (F20%):   0.375 30% Bioavailability (F30%):   0.393
50% Bioavailability (F50%):   0.315

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.243 MRP1:   0.926
Plasma Protein Binding (PPB):   97.751% Volume Distribution (VD):   0.562
Fu: 2.633%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.091
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.191
BSEP inhibitor:   0.945

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.008 CYP2C19-substrate:   0.014
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.022
CYP2D6-inhibitor:   0.348 CYP2D6-substrate:   0.99
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.444 CYP2C8-inhibitor:   1.0
HLM stability:   0.752
?
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):  5.66 Half-life (T1/2):  0.365

ADMET: Toxicity

hERG Blockers:  0.439 hERG Blockers (10um):  0.783
Human Hepatotoxicity (H-HT):  0.424 Drug-induced Liver Injury (DILI):  0.134
AMES Toxicity:  0.119 Rat Oral Acute Toxicity:  0.285
Maximum Recommended Daily Dose:  0.138 Skin Sensitization:  0.885
Carcinogencity:  0.253 Eye Corrosion:  0.997
Eye Irritation:  0.997 Respiratory Toxicity:  0.887
Drug-induced Neurotoxicity:  0.18 Ototoxicity:  0.186
Hematotoxicity:  0.21 Drug-induced Nephrotoxicity:  0.276
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.048
A549 Cytotoxicity:  0.508 Hek293 Cytotoxicity:  0.181
BCF:   1.387
?
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:   4.514
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.567
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.018
?
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
NPT166 Individual protein Acyl coenzyme A:cholesterol acyltransferase Homo sapiens Ki = 7.6 nM PMID[21733699]
NPT203 Individual protein Carboxylesterase 2 Homo sapiens Ki = 25.6 nM PMID[21733699]
NPT2610 Individual protein Acyl coenzyme A:cholesterol acyltransferase Oryctolagus cuniculus Ki = 6.5 nM PMID[21733699]
NPT204 Individual protein Acetylcholinesterase Homo sapiens Ki > 100000.0 nM PMID[21733699]
NPT203 Individual protein Carboxylesterase 2 Homo sapiens Ki = 66.8 nM PMID[21733699]
NPT203 Individual protein Carboxylesterase 2 Homo sapiens Inhibition = 92.9 % PMID[21733699]
NPT203 Individual protein Carboxylesterase 2 Homo sapiens Ki = 26.0 nM PMID[23286284]
NPT166 Individual protein Acyl coenzyme A:cholesterol acyltransferase Homo sapiens Ki = 7.6 nM PMID[23286284]
NPT439 Individual protein Butyrylcholinesterase Homo sapiens Ki > 100000.0 nM PMID[21733699]

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 NPC485345 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 NPC485344
0.7059 Intermediate Similarity NPC42403
0.7059 Intermediate Similarity NPC149101
0.7059 Intermediate Similarity NPC153439
0.7059 Intermediate Similarity NPC196434
0.7059 Intermediate Similarity NPC76608
0.7059 Intermediate Similarity NPC222997
0.7059 Intermediate Similarity NPC4962
0.7059 Intermediate Similarity NPC16578
0.7059 Intermediate Similarity NPC29561
0.7059 Intermediate Similarity NPC221192
0.6667 Remote Similarity NPC225318
0.6471 Remote Similarity NPC66624
0.6316 Remote Similarity NPC79887
0.6316 Remote Similarity NPC606898
0.6111 Remote Similarity NPC79591
0.5789 Remote Similarity NPC295442
0.5652 Remote Similarity NPC76051
0.5455 Remote Similarity NPC268596
0.5455 Remote Similarity NPC301919
0.5294 Remote Similarity NPC30338
0.5238 Remote Similarity NPC220061
0.5217 Remote Similarity NPC125129

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC485345 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