Natural Product: NPC67214

Natural Product IDNPC67214
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 GQNWYSYOSQOHAT-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 49767686
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins and derivatives

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 GQNWYSYOSQOHAT-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H22O5/c1-11(2)14(20)9-13-15(22-10-16-19(3,4)24-16)7-5-12-6-8-17(21)23-18(12)13/h5-8,11,16H,9-10H2,1-4H3
SMILES CC(C)C(=O)Cc1c(ccc2ccc(=O)oc12)OCC1C(C)(C)O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   330.15 Volume:   339.643
?
Van der Waals volume.
Dense:   0.972 LogP:   3.379
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.284
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.283
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   16.0
TPSA:   69.04
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.601 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.304 Fsp3:   0.474
MCE-18:   62.857
?
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:   0.151 Fluc inhibitor:   0.057
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.997
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.523
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.168 Promiscuous compounds:   0.008

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.807 MDCK Permeability:   -4.649
Pgp-inhibitor:   0.043 Pgp-substrate:   0.0
PAMPA:   0.034
?
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%):   0.133 30% Bioavailability (F30%):   0.067
50% Bioavailability (F50%):   0.231

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   1.0
Plasma Protein Binding (PPB):   93.61% Volume Distribution (VD):   -0.086
Fu: 5.272%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.977
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.063 CYP1A2-substrate:   0.321
CYP2C19-inhibitor:   0.989 CYP2C19-substrate:   0.029
CYP2C9-inhibitor:   0.645 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.419
CYP3A4-inhibitor:   0.368 CYP3A4-substrate:   0.977
CYP2B6-substrate:   0.226 CYP2C8-inhibitor:   0.518
HLM stability:   0.748
?
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):  8.143 Half-life (T1/2):  0.602

ADMET: Toxicity

hERG Blockers:  0.127 hERG Blockers (10um):  0.357
Human Hepatotoxicity (H-HT):  0.487 Drug-induced Liver Injury (DILI):  0.875
AMES Toxicity:  0.488 Rat Oral Acute Toxicity:  0.517
Maximum Recommended Daily Dose:  0.427 Skin Sensitization:  0.334
Carcinogencity:  0.504 Eye Corrosion:  0.008
Eye Irritation:  0.541 Respiratory Toxicity:  0.678
Drug-induced Neurotoxicity:  0.381 Ototoxicity:  0.277
Hematotoxicity:  0.361 Drug-induced Nephrotoxicity:  0.296
Genotoxicity:  0.972 RPMI-8226 Immunitoxicity:  0.04
A549 Cytotoxicity:  0.018 Hek293 Cytotoxicity:  0.291
BCF:   1.357
?
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:   4.031
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.355
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.907
?
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
NPO21771 Citrus trifoliata Species Rutaceae Eukaryota n.a. fruit n.a. PMID[23872723]
NPO21771 Citrus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[32996318]
NPO21771 Citrus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21771 Citrus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21771 Citrus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO21771 Citrus trifoliata Species Rutaceae 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

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 NPC67214 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
0.7333 Intermediate Similarity NPC479312
0.7273 Intermediate Similarity NPC55147
0.7143 Intermediate Similarity NPC479308
0.7049 Intermediate Similarity NPC479309
0.6154 Remote Similarity NPC469675
0.6102 Remote Similarity NPC80170
0.6 Remote Similarity NPC104796
0.5645 Remote Similarity NPC54503
0.5538 Remote Similarity NPC479313
0.5441 Remote Similarity NPC479311
0.5397 Remote Similarity NPC33986
0.5373 Remote Similarity NPC472424
0.5373 Remote Similarity NPC281241
0.5323 Remote Similarity NPC96286
0.5286 Remote Similarity NPC479310
0.5156 Remote Similarity NPC188380
0.5156 Remote Similarity NPC224543
0.5143 Remote Similarity NPC55149
0.5079 Remote Similarity NPC472516

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC67214 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