Natural Product: NPC604715

Natural Product IDNPC604715
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 YQNPVOBVGNGYHD-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL4101262
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 YQNPVOBVGNGYHD-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H16O5/c1-21-12-5-2-10(3-6-12)4-7-13(18)16-14(19)8-11(17)9-15(16)20/h2-3,5-6,8-9,17,19-20H,4,7H2,1H3
SMILES COc1ccc(CCC(=O)c2c(O)cc(O)cc2O)cc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   288.1 Volume:   293.675
?
Van der Waals volume.
Dense:   0.981 LogP:   3.047
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.115
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.635
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   13.0
TPSA:   86.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.736 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.057 Fsp3:   0.188
MCE-18:   13.0
?
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:   0.492 Fluc inhibitor:   0.623
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.23
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.304
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.63 Promiscuous compounds:   0.139

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.852 MDCK Permeability:   -4.832
Pgp-inhibitor:   0.904 Pgp-substrate:   0.027
PAMPA:   0.063
?
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%):   0.013 30% Bioavailability (F30%):   0.671
50% Bioavailability (F50%):   0.962

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.73
Plasma Protein Binding (PPB):   96.691% Volume Distribution (VD):   0.048
Fu: 2.841%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.995
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.941
BSEP inhibitor:   0.96

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.292 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.988
CYP3A4-inhibitor:   0.092 CYP3A4-substrate:   0.306
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.999
?
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):  8.542 Half-life (T1/2):  0.944

ADMET: Toxicity

hERG Blockers:  0.129 hERG Blockers (10um):  0.614
Human Hepatotoxicity (H-HT):  0.407 Drug-induced Liver Injury (DILI):  0.072
AMES Toxicity:  0.393 Rat Oral Acute Toxicity:  0.279
Maximum Recommended Daily Dose:  0.616 Skin Sensitization:  0.541
Carcinogencity:  0.394 Eye Corrosion:  0.122
Eye Irritation:  0.991 Respiratory Toxicity:  0.945
Drug-induced Neurotoxicity:  0.386 Ototoxicity:  0.152
Hematotoxicity:  0.156 Drug-induced Nephrotoxicity:  0.145
Genotoxicity:  0.71 RPMI-8226 Immunitoxicity:  0.047
A549 Cytotoxicity:  0.303 Hek293 Cytotoxicity:  0.646
BCF:   1.701
?
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:   3.958
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.423
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.616
?
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
NPO21410 Populus balsamifera Species Salicaceae Eukaryota Buds n.a. n.a. PMID[25927817]
NPO21410 Populus balsamifera Species Salicaceae Eukaryota n.a. n.a. n.a. PMID[38612781]
NPO63332 Populus trichocarpa Species Salicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21409 Populus angustifolia Species Salicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO42242 Iryanthera laevis Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO54056 Populus deltoides Species Salicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21410 Populus balsamifera Species Salicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21410 Populus balsamifera Species Salicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21410 Populus balsamifera Species Salicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21410 Populus balsamifera Species Salicaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21410 Populus balsamifera Species Salicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21409 Populus angustifolia Species Salicaceae 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
NPT641 Individual protein Sodium/glucose cotransporter 2 Homo sapiens Inhibition n.a. n.a. % PMID[28098449]
NPT641 Individual protein Sodium/glucose cotransporter 2 Homo sapiens IC50 = 18700.0 nM PMID[28098449]
NPT640 Individual protein Sodium/glucose cotransporter 1 Homo sapiens Inhibition n.a. n.a. % PMID[28098449]
NPT640 Individual protein Sodium/glucose cotransporter 1 Homo sapiens IC50 = 13300.0 nM PMID[28098449]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT71 Cell line HEK293 Homo sapiens Activity n.a. n.a. n.a. PMID[28098449]
NPT28438 Unchecked Unchecked n.a. Inhibition n.a. n.a. % PMID[28098449]

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 NPC604715 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
0.8 Intermediate Similarity NPC204960
0.7333 Intermediate Similarity NPC20560
0.7073 Intermediate Similarity NPC242895
0.7073 Intermediate Similarity NPC607946
0.6818 Remote Similarity NPC82225
0.6591 Remote Similarity NPC294593
0.6522 Remote Similarity NPC144051
0.6364 Remote Similarity NPC233056
0.617 Remote Similarity NPC286336
0.5957 Remote Similarity NPC485643
0.5652 Remote Similarity NPC179494
0.56 Remote Similarity NPC18877
0.5417 Remote Similarity NPC164236
0.54 Remote Similarity NPC28753
0.5385 Remote Similarity NPC282957
0.5217 Remote Similarity NPC133909
0.52 Remote Similarity NPC189106
0.5192 Remote Similarity NPC194949
0.5179 Remote Similarity NPC234152

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC604715 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