Natural Product: NPC606140

Natural Product IDNPC606140
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 WVBTWALEDCJRKA-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL166376
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 WVBTWALEDCJRKA-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H18O4/c1-12(2)8-9-14-15(21)10-16(22)19-17(23)11-18(24-20(14)19)13-6-4-3-5-7-13/h3-8,10-11,21-22H,9H2,1-2H3
SMILES CC(C)=CCc1c(O)cc(O)c2c(=O)cc(-c3ccccc3)oc12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   322.12 Volume:   340.24
?
Van der Waals volume.
Dense:   0.947 LogP:   4.573
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.619
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.933
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   19.0
TPSA:   70.67
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.702 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.541 Fsp3:   0.15
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:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.912 Fluc inhibitor:   0.522
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.989
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.821
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.264 Promiscuous compounds:   0.135

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.974 MDCK Permeability:   -4.697
Pgp-inhibitor:   0.94 Pgp-substrate:   0.075
PAMPA:   0.109
?
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):   0.006
20% Bioavailability (F20%):   0.305 30% Bioavailability (F30%):   0.898
50% Bioavailability (F50%):   0.957

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.095 MRP1:   0.957
Plasma Protein Binding (PPB):   97.434% Volume Distribution (VD):   0.262
Fu: 2.323%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.981
OATP1B3 inhibitor:   0.91 BCRP inhibitor:   0.771
BSEP inhibitor:   0.986

ADMET: Metabolism

CYP1A2-inhibitor:   0.004 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.99 CYP2C19-substrate:   0.997
CYP2C9-inhibitor:   0.512 CYP2C9-substrate:   0.883
CYP2D6-inhibitor:   0.972 CYP2D6-substrate:   0.474
CYP3A4-inhibitor:   0.012 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  4.305 Half-life (T1/2):  1.145

ADMET: Toxicity

hERG Blockers:  0.046 hERG Blockers (10um):  0.531
Human Hepatotoxicity (H-HT):  0.512 Drug-induced Liver Injury (DILI):  0.898
AMES Toxicity:  0.673 Rat Oral Acute Toxicity:  0.741
Maximum Recommended Daily Dose:  0.683 Skin Sensitization:  0.838
Carcinogencity:  0.586 Eye Corrosion:  0.007
Eye Irritation:  0.929 Respiratory Toxicity:  0.956
Drug-induced Neurotoxicity:  0.094 Ototoxicity:  0.108
Hematotoxicity:  0.117 Drug-induced Nephrotoxicity:  0.115
Genotoxicity:  0.982 RPMI-8226 Immunitoxicity:  0.053
A549 Cytotoxicity:  0.294 Hek293 Cytotoxicity:  0.605
BCF:   1.769
?
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:   4.682
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.046
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.52
?
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
NPO61345 Platanus acerifolia Species Platanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT139 Cell line HT-29 Homo sapiens Activity = 86.3 n.a. PMID[15828817]
NPT139 Cell line HT-29 Homo sapiens Activity = 75.5 n.a. PMID[15828817]
NPT139 Cell line HT-29 Homo sapiens Caspase induction = 0.9 n.a. PMID[15828817]
NPT111 Cell line K562 Homo sapiens Relative daunomycin accumulation = 1.52 n.a. PMID[11262086]

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
n.a. n.a. LogP = 6.2 n.a. PMID[11262086]





 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 NPC606140 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
0.8333 Intermediate Similarity NPC220062
0.7857 Intermediate Similarity NPC88804
0.7679 Intermediate Similarity NPC482025
0.7458 Intermediate Similarity NPC216978
0.7167 Intermediate Similarity NPC601414
0.6615 Remote Similarity NPC471982
0.6102 Remote Similarity NPC482938
0.6056 Remote Similarity NPC471985
0.6032 Remote Similarity NPC482709
0.5968 Remote Similarity NPC9117
0.5968 Remote Similarity NPC63187
0.5606 Remote Similarity NPC488612
0.5606 Remote Similarity NPC293053
0.5606 Remote Similarity NPC273538
0.5522 Remote Similarity NPC349460
0.5522 Remote Similarity NPC605239
0.5373 Remote Similarity NPC482074
0.5373 Remote Similarity NPC59162
0.5373 Remote Similarity NPC96565
0.5345 Remote Similarity NPC78540
0.5345 Remote Similarity NPC259713
0.5294 Remote Similarity NPC301217
0.5286 Remote Similarity NPC327005
0.5286 Remote Similarity NPC602981
0.5246 Remote Similarity NPC131624
0.5231 Remote Similarity NPC32463
0.5161 Remote Similarity NPC482122
0.5152 Remote Similarity NPC227122
0.5152 Remote Similarity NPC70433
0.5152 Remote Similarity NPC284220
0.5082 Remote Similarity NPC201395
0.5079 Remote Similarity NPC53181
0.5079 Remote Similarity NPC606332
0.5075 Remote Similarity NPC144118
0.5072 Remote Similarity NPC475799
0.5072 Remote Similarity NPC14871

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC606140 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
0.5606 Remote Similarity NPD4378 Phase 3
0.5068 Remote Similarity NPD4419 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