Natural Product: NPC480478

Natural Product IDNPC480478
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JYHURUUEYIBYEH-UBJUHAIHSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 134138993
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 JYHURUUEYIBYEH-UBJUHAIHSA-N
Standard InCHI InChI=1S/C13H14O4/c1-7-8(2)13(14)17-12(7)9-3-4-10-11(5-9)16-6-15-10/h3-5,7-8,12H,6H2,1-2H3/t7-,8-,12-/m0/s1
SMILES C[C@H]1[C@H](C)C(=O)O[C@@H]1c1ccc2c(c1)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   234.09 Volume:   232.35
?
Van der Waals volume.
Dense:   1.007 LogP:   2.401
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.297
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.908
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   16.0
TPSA:   44.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.699 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.339 Fsp3:   0.462
MCE-18:   54.737
?
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:   0.102 Fluc inhibitor:   0.61
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.051
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.069
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.543 Promiscuous compounds:   0.469

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.756 MDCK Permeability:   -4.492
Pgp-inhibitor:   0.432 Pgp-substrate:   0.022
PAMPA:   0.675
?
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):   0.001
20% Bioavailability (F20%):   0.024 30% Bioavailability (F30%):   0.001
50% Bioavailability (F50%):   0.115

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.163 MRP1:   0.917
Plasma Protein Binding (PPB):   95.032% Volume Distribution (VD):   -0.265
Fu: 5.366%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.809
OATP1B3 inhibitor:   0.903 BCRP inhibitor:   0.014
BSEP inhibitor:   0.993

ADMET: Metabolism

CYP1A2-inhibitor:   0.956 CYP1A2-substrate:   0.991
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.112
CYP2C9-inhibitor:   0.825 CYP2C9-substrate:   0.908
CYP2D6-inhibitor:   0.305 CYP2D6-substrate:   0.997
CYP3A4-inhibitor:   0.215 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.828 CYP2C8-inhibitor:   0.0
HLM stability:   0.872
?
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):  5.103 Half-life (T1/2):  1.395

ADMET: Toxicity

hERG Blockers:  0.074 hERG Blockers (10um):  0.428
Human Hepatotoxicity (H-HT):  0.66 Drug-induced Liver Injury (DILI):  0.957
AMES Toxicity:  0.679 Rat Oral Acute Toxicity:  0.395
Maximum Recommended Daily Dose:  0.251 Skin Sensitization:  0.837
Carcinogencity:  0.904 Eye Corrosion:  0.791
Eye Irritation:  0.974 Respiratory Toxicity:  0.63
Drug-induced Neurotoxicity:  0.657 Ototoxicity:  0.224
Hematotoxicity:  0.699 Drug-induced Nephrotoxicity:  0.707
Genotoxicity:  0.786 RPMI-8226 Immunitoxicity:  0.081
A549 Cytotoxicity:  0.228 Hek293 Cytotoxicity:  0.225
BCF:   1.574
?
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:   3.86
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.547
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.882
?
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
NPO8247 Austrobaileya scandens Species Austrobaileyaceae Eukaryota n.a. n.a. n.a. PMID[27214307]
NPO8247 Austrobaileya scandens Species Austrobaileyaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8247 Austrobaileya scandens Species Austrobaileyaceae 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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 15.0 % PMID[27214307]

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 NPC480478 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
0.725 Intermediate Similarity NPC271208
0.725 Intermediate Similarity NPC233224
0.725 Intermediate Similarity NPC610263
0.6667 Remote Similarity NPC483654
0.6591 Remote Similarity NPC57119
0.6591 Remote Similarity NPC158471
0.6591 Remote Similarity NPC226862
0.617 Remote Similarity NPC487685
0.6136 Remote Similarity NPC171928
0.6136 Remote Similarity NPC158526
0.6136 Remote Similarity NPC129687
0.6136 Remote Similarity NPC33611
0.6136 Remote Similarity NPC16830
0.6136 Remote Similarity NPC100223
0.6 Remote Similarity NPC165128
0.58 Remote Similarity NPC14022
0.58 Remote Similarity NPC601703
0.566 Remote Similarity NPC483653
0.5625 Remote Similarity NPC227160
0.5625 Remote Similarity NPC82111
0.5577 Remote Similarity NPC135777
0.5577 Remote Similarity NPC7744
0.5536 Remote Similarity NPC254163
0.551 Remote Similarity NPC136750
0.551 Remote Similarity NPC266848
0.5472 Remote Similarity NPC142547
0.5472 Remote Similarity NPC228469
0.5472 Remote Similarity NPC488984
0.5472 Remote Similarity NPC488985
0.54 Remote Similarity NPC189474
0.5185 Remote Similarity NPC24257
0.5185 Remote Similarity NPC153620
0.5167 Remote Similarity NPC308555
0.5122 Remote Similarity NPC269340

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC480478 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