Natural Product: NPC43361

Natural Product IDNPC43361
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 DVKUEUADFHEKNX-BMGYHDIPSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 23427580
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0003909] Fatty Acyls
        • [CHEMONTID:0000504] Lineolic acids and derivatives

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 DVKUEUADFHEKNX-BMGYHDIPSA-N
Standard InCHI InChI=1S/C18H30O4/c1-2-3-4-7-10-13-16(19)17(20)14-11-8-5-6-9-12-15-18(21)22/h5,8,10-11,13-14,16-17,19-20H,2-4,6-7,9,12,15H2,1H3,(H,21,22)/b8-5-,13-10-,14-11+/t16-,17-/m1/s1
SMILES CCCCC/C=C[C@H]([C@@H](/C=C/C=CCCCCC(=O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   310.21 Volume:   344.499
?
Van der Waals volume.
Dense:   0.9 LogP:   3.498
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.836
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.283
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   13.0 Rigid Bonds:   4.0
TPSA:   77.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   3.0 Rings:   0.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.276 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.552 Fsp3:   0.611
MCE-18:   3.0
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.154 Fluc inhibitor:   0.014
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.017
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.003
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.901 Promiscuous compounds:   0.375

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.274 MDCK Permeability:   -5.183
Pgp-inhibitor:   0.001 Pgp-substrate:   0.006
PAMPA:   0.923
?
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):   0.015
20% Bioavailability (F20%):   0.403 30% Bioavailability (F30%):   0.909
50% Bioavailability (F50%):   0.717

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.263
Plasma Protein Binding (PPB):   95.969% Volume Distribution (VD):   -0.685
Fu: 3.224%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.201
OATP1B3 inhibitor:   0.978 BCRP inhibitor:   0.019
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.077
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.115
CYP2B6-substrate:   0.028 CYP2C8-inhibitor:   0.835
HLM stability:   0.006
?
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):  6.083 Half-life (T1/2):  0.885

ADMET: Toxicity

hERG Blockers:  0.11 hERG Blockers (10um):  0.214
Human Hepatotoxicity (H-HT):  0.301 Drug-induced Liver Injury (DILI):  0.006
AMES Toxicity:  0.182 Rat Oral Acute Toxicity:  0.083
Maximum Recommended Daily Dose:  0.207 Skin Sensitization:  0.999
Carcinogencity:  0.04 Eye Corrosion:  0.69
Eye Irritation:  0.959 Respiratory Toxicity:  0.438
Drug-induced Neurotoxicity:  0.011 Ototoxicity:  0.73
Hematotoxicity:  0.082 Drug-induced Nephrotoxicity:  0.732
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.066
A549 Cytotoxicity:  0.364 Hek293 Cytotoxicity:  0.183
BCF:   0.665
?
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:   3.465
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.701
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.508
?
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
NPO21178 Chloranthus serratus Species Chloranthaceae Eukaryota n.a. n.a. n.a. PMID[19053511]
NPO21178 Chloranthus serratus Species Chloranthaceae Eukaryota n.a. n.a. n.a. PMID[22372956]
NPO21178 Chloranthus serratus Species Chloranthaceae Eukaryota n.a. n.a. n.a. PMID[27588583]
NPO2989 Atalantia monophylla Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[28140592]
NPO21178 Chloranthus serratus Species Chloranthaceae Eukaryota n.a. n.a. n.a. PMID[30724564]
NPO2989 Atalantia monophylla Species Rutaceae Eukaryota Seeds n.a. n.a. PMID[31390210]
NPO2989 Atalantia monophylla Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21178 Chloranthus serratus Species Chloranthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21178 Chloranthus serratus Species Chloranthaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2989 Atalantia monophylla Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21178 Chloranthus serratus Species Chloranthaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2989 Atalantia monophylla Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21178 Chloranthus serratus Species Chloranthaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21178 Chloranthus serratus Species Chloranthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2989 Atalantia monophylla Species Rutaceae 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

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 NPC43361 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
0.7209 Intermediate Similarity NPC255863
0.7209 Intermediate Similarity NPC136164
0.7209 Intermediate Similarity NPC245947
0.6842 Remote Similarity NPC95145
0.6842 Remote Similarity NPC325642
0.6842 Remote Similarity NPC65174
0.6154 Remote Similarity NPC424
0.6154 Remote Similarity NPC36061
0.6154 Remote Similarity NPC69510
0.6154 Remote Similarity NPC77272
0.6154 Remote Similarity NPC290563
0.6154 Remote Similarity NPC139029
0.6154 Remote Similarity NPC281972
0.6154 Remote Similarity NPC92114
0.6154 Remote Similarity NPC261831
0.6154 Remote Similarity NPC87564
0.6042 Remote Similarity NPC323045
0.6042 Remote Similarity NPC317881
0.5897 Remote Similarity NPC281245
0.5854 Remote Similarity NPC321062
0.5854 Remote Similarity NPC5413
0.58 Remote Similarity NPC605544
0.58 Remote Similarity NPC607260
0.5745 Remote Similarity NPC243532
0.5714 Remote Similarity NPC154245
0.5714 Remote Similarity NPC85813
0.5714 Remote Similarity NPC223697
0.5714 Remote Similarity NPC49863
0.5714 Remote Similarity NPC6095
0.5625 Remote Similarity NPC318420
0.5625 Remote Similarity NPC325627
0.5625 Remote Similarity NPC326268
0.5556 Remote Similarity NPC606120
0.551 Remote Similarity NPC327112
0.5455 Remote Similarity NPC318306
0.5417 Remote Similarity NPC251042
0.5417 Remote Similarity NPC99619
0.5417 Remote Similarity NPC174447
0.5417 Remote Similarity NPC122521
0.5306 Remote Similarity NPC323477
0.52 Remote Similarity NPC470320
0.5135 Remote Similarity NPC155263
0.5116 Remote Similarity NPC91495
0.5116 Remote Similarity NPC324004
0.5116 Remote Similarity NPC328497
0.5116 Remote Similarity NPC70387

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC43361 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
0.6154 Remote Similarity NPD3195 Phase 2
0.6154 Remote Similarity NPD3196 Approved
0.5909 Remote Similarity NPD3194 Phase 4
0.5854 Remote Similarity NPD3173 Phase 4
0.5714 Remote Similarity NPD4247 Clinical (unspecified phase)
0.5714 Remote Similarity NPD4266 Phase 2
0.551 Remote Similarity NPD4246 Phase 2

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