Natural Product: NPC96122

Natural Product IDNPC96122
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 PTVAOGIYBMTHSN-WAYWQWQTSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 46898027
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 PTVAOGIYBMTHSN-WAYWQWQTSA-N
Standard InCHI InChI=1S/C18H20O4/c1-19-15-9-14(10-16(12-15)20-2)6-5-13-7-8-17(21-3)18(11-13)22-4/h5-12H,1-4H3/b6-5-
SMILES COc1cc(/C=Cc2ccc(c(c2)OC)OC)cc(c1)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.14 Volume:   319.477
?
Van der Waals volume.
Dense:   0.939 LogP:   3.599
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.806
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.075
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   13.0
TPSA:   36.92
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.758 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.868 Fsp3:   0.222
MCE-18:   12.0
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.886 Fluc inhibitor:   0.999
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.12
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.605
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.687 Promiscuous compounds:   0.21

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.733 MDCK Permeability:   -4.685
Pgp-inhibitor:   0.996 Pgp-substrate:   0.002
PAMPA:   0.0
?
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):   0.038
20% Bioavailability (F20%):   0.042 30% Bioavailability (F30%):   0.016
50% Bioavailability (F50%):   0.229

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.026 MRP1:   0.057
Plasma Protein Binding (PPB):   77.601% Volume Distribution (VD):   -0.153
Fu: 16.046%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.996
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.996 CYP1A2-substrate:   0.533
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.008
CYP2C9-inhibitor:   0.955 CYP2C9-substrate:   0.656
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.994
CYP3A4-inhibitor:   0.061 CYP3A4-substrate:   0.023
CYP2B6-substrate:   0.982 CYP2C8-inhibitor:   0.995
HLM stability:   0.694
?
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):  10.53 Half-life (T1/2):  1.142

ADMET: Toxicity

hERG Blockers:  0.543 hERG Blockers (10um):  0.741
Human Hepatotoxicity (H-HT):  0.678 Drug-induced Liver Injury (DILI):  0.133
AMES Toxicity:  0.792 Rat Oral Acute Toxicity:  0.451
Maximum Recommended Daily Dose:  0.773 Skin Sensitization:  0.969
Carcinogencity:  0.609 Eye Corrosion:  0.001
Eye Irritation:  0.736 Respiratory Toxicity:  0.325
Drug-induced Neurotoxicity:  0.893 Ototoxicity:  0.683
Hematotoxicity:  0.169 Drug-induced Nephrotoxicity:  0.842
Genotoxicity:  0.033 RPMI-8226 Immunitoxicity:  0.321
A549 Cytotoxicity:  0.832 Hek293 Cytotoxicity:  0.757
BCF:   2.137
?
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:   3.98
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.295
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.842
?
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
NPO40842 Eugenia rigida Species n.a. n.a. n.a. n.a. n.a. PMID[23547843]
NPO40842 Eugenia rigida Species n.a. n.a. n.a. n.a. n.a. PMID[27618204]
NPO40842 Eugenia rigida Species n.a. n.a. 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
NPT3961 Individual protein Forkhead box protein O1 Homo sapiens Inhibition < 40.0 % PMID[23547843]
NPT3962 Individual protein Myc proto-oncogene protein Homo sapiens IC50 = 60000.0 nM PMID[23547843]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT660 Cell line SW480 Homo sapiens IC50 = 9500.0 nM PMID[20395019]
NPT165 Cell line HeLa Homo sapiens IC50 = 40000.0 nM PMID[23547843]
NPT165 Cell line HeLa Homo sapiens IC50 = 50000.0 nM PMID[23547843]
NPT189 Cell line Vero Chlorocebus aethiops IC50 > 33300.0 nM PMID[23547843]
NPT857 Cell line LLC-PK1 Sus scrofa IC50 = 6000.0 nM PMID[23547843]
NPT165 Cell line HeLa Homo sapiens IC50 = 3600.0 nM PMID[23547843]
NPT916 Cell line SK-MEL Homo sapiens IC50 = 4300.0 nM PMID[23547843]
NPT457 Cell line BT-549 Homo sapiens IC50 = 4000.0 nM PMID[23547843]
NPT91 Cell line KB Homo sapiens IC50 = 4300.0 nM PMID[23547843]
NPT116 Cell line HL-60 Homo sapiens IC50 = 4300.0 nM PMID[23547843]
NPT169 Cell line B16-F10 Mus musculus Inhibition = 80.0 % PMID[32485531]
NPT169 Cell line B16-F10 Mus musculus IC50 = 1000.0 nM PMID[32485531]
NPT610 Others Molecular identity unknown n.a. Inhibition < 40.0 % PMID[23547843]
NPT610 Others Molecular identity unknown n.a. IC50 = 40000.0 nM PMID[23547843]
NPT610 Others Molecular identity unknown n.a. IC50 = 80000.0 nM PMID[23547843]

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 NPC96122 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 NPC123948
0.7742 Intermediate Similarity NPC82016
0.625 Remote Similarity NPC166759
0.6176 Remote Similarity NPC35543
0.5897 Remote Similarity NPC473411
0.5897 Remote Similarity NPC474565
0.5714 Remote Similarity NPC310905
0.5686 Remote Similarity NPC473412
0.5526 Remote Similarity NPC228287
0.5526 Remote Similarity NPC180508
0.55 Remote Similarity NPC71579
0.549 Remote Similarity NPC469698
0.5405 Remote Similarity NPC179309
0.5263 Remote Similarity NPC475961
0.525 Remote Similarity NPC294941
0.5128 Remote Similarity NPC227894
0.5128 Remote Similarity NPC185738

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC96122 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
0.6053 Remote Similarity NPD2981 Phase 2
0.5897 Remote Similarity NPD2983 Phase 3
0.5128 Remote Similarity NPD5536 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