Natural Product: NPC605332

Natural Product IDNPC605332
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CKDYDMSDCNQHEB-CVEARBPZSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3634579
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 CKDYDMSDCNQHEB-CVEARBPZSA-N
Standard InCHI InChI=1S/C16H14O6/c1-21-10-4-2-8(3-5-10)16-15(20)14(19)13-11(18)6-9(17)7-12(13)22-16/h2-7,15-18,20H,1H3/t15-,16+/m1/s1
SMILES COc1ccc([C@@H]2Oc3cc(O)cc(O)c3C(=O)[C@H]2O)cc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   302.08 Volume:   293.909
?
Van der Waals volume.
Dense:   1.028 LogP:   1.752
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.034
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.978
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   96.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.782 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.077 Fsp3:   0.188
MCE-18:   57.789
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.462 Fluc inhibitor:   0.652
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.121
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.279
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.389 Promiscuous compounds:   0.276

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.71 MDCK Permeability:   -4.95
Pgp-inhibitor:   0.867 Pgp-substrate:   0.363
PAMPA:   0.141
?
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):   0.115
20% Bioavailability (F20%):   0.083 30% Bioavailability (F30%):   0.871
50% Bioavailability (F50%):   0.977

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.006 MRP1:   0.683
Plasma Protein Binding (PPB):   95.489% Volume Distribution (VD):   0.084
Fu: 3.676%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.992
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.936
BSEP inhibitor:   0.493

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.019 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.969 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.959 CYP2D6-substrate:   0.363
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.061
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.983
HLM stability:   0.25
?
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):  9.856 Half-life (T1/2):  1.523

ADMET: Toxicity

hERG Blockers:  0.109 hERG Blockers (10um):  0.423
Human Hepatotoxicity (H-HT):  0.562 Drug-induced Liver Injury (DILI):  0.647
AMES Toxicity:  0.685 Rat Oral Acute Toxicity:  0.257
Maximum Recommended Daily Dose:  0.533 Skin Sensitization:  0.744
Carcinogencity:  0.359 Eye Corrosion:  0.011
Eye Irritation:  0.958 Respiratory Toxicity:  0.809
Drug-induced Neurotoxicity:  0.297 Ototoxicity:  0.461
Hematotoxicity:  0.25 Drug-induced Nephrotoxicity:  0.539
Genotoxicity:  0.948 RPMI-8226 Immunitoxicity:  0.16
A549 Cytotoxicity:  0.307 Hek293 Cytotoxicity:  0.586
BCF:   1.065
?
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:   3.765
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.888
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.171
?
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
NPO7546 Prunus domestica Species Rosaceae Eukaryota n.a. kernel n.a. PMID[12232058]
NPO7546 Prunus domestica Species Rosaceae Eukaryota n.a. fruit n.a. PMID[21648406]
NPO7546 Prunus domestica Species Rosaceae Eukaryota n.a. n.a. n.a. PMID[38279238]
NPO24693 Prunus cerasus Species Rosaceae Eukaryota n.a. n.a. n.a. PMID[9917288]
NPO25019 Salix caprea Species Salicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO43142 Prunus communis Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7546 Prunus domestica Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24693 Prunus cerasus Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7546 Prunus domestica Species Rosaceae Eukaryota n.a. n.a. Database[FooDB]
NPO24693 Prunus cerasus Species Rosaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO7546 Prunus domestica Species Rosaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO24693 Prunus cerasus Species Rosaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO7546 Prunus domestica Species Rosaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO24693 Prunus cerasus Species Rosaceae Eukaryota n.a. n.a. Database[FooDB]
NPO24693 Prunus cerasus Species Rosaceae Eukaryota Fruits n.a. Database[FooDB]
NPO7546 Prunus domestica Species Rosaceae Eukaryota Fruits n.a. Database[FooDB]
NPO25019 Salix caprea Species Salicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7546 Prunus domestica Species Rosaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24693 Prunus cerasus Species Rosaceae Eukaryota Fruits n.a. Database[Phenol-Explorer]
NPO7546 Prunus domestica Species Rosaceae Eukaryota Fruits n.a. Database[Phenol-Explorer]
NPO7546 Prunus domestica Species Rosaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO25019 Salix caprea Species Salicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7546 Prunus domestica Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7546 Prunus domestica Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24693 Prunus cerasus Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25019 Salix caprea 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT113 Cell line RAW264.7 Mus musculus Inhibition < 10.0 % PMID[26481151]
NPT28833 No target No relevant target n.a. EC50 > 100000.0 nM PMID[26481151]

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 NPC605332 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 NPC44721
1.0 High Similarity NPC211466
0.7917 Intermediate Similarity NPC62290
0.7917 Intermediate Similarity NPC142731
0.7917 Intermediate Similarity NPC326506
0.7917 Intermediate Similarity NPC4152
0.7843 Intermediate Similarity NPC320825
0.78 Intermediate Similarity NPC250922
0.7347 Intermediate Similarity NPC21835
0.7222 Intermediate Similarity NPC326037
0.7222 Intermediate Similarity NPC13858
0.7115 Intermediate Similarity NPC36835
0.7115 Intermediate Similarity NPC246162
0.7115 Intermediate Similarity NPC9743
0.7115 Intermediate Similarity NPC260491
0.7115 Intermediate Similarity NPC61506
0.7115 Intermediate Similarity NPC240476
0.7059 Intermediate Similarity NPC19721
0.6863 Remote Similarity NPC279417
0.6863 Remote Similarity NPC49130
0.6604 Remote Similarity NPC176869
0.6604 Remote Similarity NPC306607
0.6604 Remote Similarity NPC3779
0.6538 Remote Similarity NPC208176
0.6415 Remote Similarity NPC122828
0.6296 Remote Similarity NPC606962
0.6111 Remote Similarity NPC274784
0.6111 Remote Similarity NPC287789
0.6111 Remote Similarity NPC20709
0.5882 Remote Similarity NPC36916
0.5882 Remote Similarity NPC36
0.5882 Remote Similarity NPC7154
0.5882 Remote Similarity NPC125039
0.5882 Remote Similarity NPC7688
0.5797 Remote Similarity NPC138688
0.5797 Remote Similarity NPC72787
0.5797 Remote Similarity NPC217795
0.5797 Remote Similarity NPC58223
0.5741 Remote Similarity NPC476182
0.5714 Remote Similarity NPC263449
0.566 Remote Similarity NPC1940
0.5614 Remote Similarity NPC609065
0.5588 Remote Similarity NPC606364
0.5536 Remote Similarity NPC201837
0.5493 Remote Similarity NPC279209
0.5493 Remote Similarity NPC102277
0.5493 Remote Similarity NPC479117
0.5455 Remote Similarity NPC148011
0.5455 Remote Similarity NPC63438
0.5439 Remote Similarity NPC481903
0.5424 Remote Similarity NPC471515
0.5345 Remote Similarity NPC61946
0.5323 Remote Similarity NPC271741
0.5246 Remote Similarity NPC20907
0.5205 Remote Similarity NPC75827
0.5172 Remote Similarity NPC308992
0.5167 Remote Similarity NPC52530

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC605332 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
0.5882 Remote Similarity NPD6166 Phase 2
0.5882 Remote Similarity NPD6167 Clinical (unspecified phase)
0.5882 Remote Similarity NPD6168 Clinical (unspecified phase)

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