Natural Product: NPC485418

Natural Product IDNPC485418
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 NICQCGJTFKXBAZ-HOCLYGCPSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
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 NICQCGJTFKXBAZ-HOCLYGCPSA-N
Standard InCHI InChI=1S/C19H16O8/c1-24-19-17-10(3-5-15(23)27-17)7-13-18(19)26-14(8-20)16(25-13)9-2-4-11(21)12(22)6-9/h2-7,14,16,20-22H,8H2,1H3/t14-,16-/m0/s1
SMILES COc1c2c(ccc(=O)o2)cc2c1O[C@@H](CO)[C@H](c1ccc(c(c1)O)O)O2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   372.08 Volume:   352.184
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Van der Waals volume.
Dense:   1.056 LogP:   1.443
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.794
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.772
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   23.0
TPSA:   118.59
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.472 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.58 Fsp3:   0.211
MCE-18:   73.0
?
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:   1 PAINS Alert:   1
Colloidal aggregators:   0.672 Fluc inhibitor:   0.566
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.923
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.419
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.234 Promiscuous compounds:   0.579

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.56 MDCK Permeability:   -5.012
Pgp-inhibitor:   0.0 Pgp-substrate:   0.0
PAMPA:   0.886
?
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):   0.0
20% Bioavailability (F20%):   0.815 30% Bioavailability (F30%):   0.939
50% Bioavailability (F50%):   0.92

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.998
Plasma Protein Binding (PPB):   79.94% Volume Distribution (VD):   -0.005
Fu: 15.834%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.766
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.0
BSEP inhibitor:   0.596

ADMET: Metabolism

CYP1A2-inhibitor:   0.234 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.005
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.024
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.999
CYP3A4-inhibitor:   0.688 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.961
HLM stability:   0.014
?
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):  12.448 Half-life (T1/2):  1.722

ADMET: Toxicity

hERG Blockers:  0.069 hERG Blockers (10um):  0.279
Human Hepatotoxicity (H-HT):  0.704 Drug-induced Liver Injury (DILI):  0.819
AMES Toxicity:  0.79 Rat Oral Acute Toxicity:  0.263
Maximum Recommended Daily Dose:  0.277 Skin Sensitization:  0.995
Carcinogencity:  0.694 Eye Corrosion:  0.038
Eye Irritation:  0.959 Respiratory Toxicity:  0.134
Drug-induced Neurotoxicity:  0.217 Ototoxicity:  0.643
Hematotoxicity:  0.156 Drug-induced Nephrotoxicity:  0.221
Genotoxicity:  0.953 RPMI-8226 Immunitoxicity:  0.037
A549 Cytotoxicity:  0.517 Hek293 Cytotoxicity:  0.32
BCF:   0.9
?
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:   3.565
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.998
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.374
?
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
NPO41069 Sapium discolor Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[30350995]

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
NPT34 Cell line BV-2 Mus musculus IC50 = 4200.0 nM PMID[30350995]

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 NPC485418 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 NPC485419
0.7083 Intermediate Similarity NPC120426
0.7059 Intermediate Similarity NPC485421
0.7059 Intermediate Similarity NPC485417
0.7059 Intermediate Similarity NPC485416
0.7059 Intermediate Similarity NPC485420
0.7 Intermediate Similarity NPC21184
0.6912 Remote Similarity NPC15577
0.6761 Remote Similarity NPC205727
0.6351 Remote Similarity NPC476347
0.6216 Remote Similarity NPC476348
0.6027 Remote Similarity NPC187398
0.5789 Remote Similarity NPC294522
0.5714 Remote Similarity NPC142614
0.56 Remote Similarity NPC176903
0.5422 Remote Similarity NPC30688
0.5393 Remote Similarity NPC163598
0.5227 Remote Similarity NPC120774
0.5161 Remote Similarity NPC244799
0.5055 Remote Similarity NPC264875

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC485418 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