Natural Product: NPC479310

Natural Product IDNPC479310
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ONEVQKKWVZFLEZ-JKSUJKDBSA-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 ONEVQKKWVZFLEZ-JKSUJKDBSA-N
Standard InCHI InChI=1S/C20H28O7/c1-19(2,24)15(21)10-13-14(26-11-16(22)20(3,4)25-5)8-6-12-7-9-17(23)27-18(12)13/h6-9,15-16,21-22,24H,10-11H2,1-5H3/t15-,16+/m0/s1
SMILES CC(C)([C@H](Cc1c(ccc2ccc(=O)oc12)OC[C@H](C(C)(C)OC)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   380.18 Volume:   385.713
?
Van der Waals volume.
Dense:   0.986 LogP:   2.042
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.257
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.714
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   12.0
TPSA:   109.36
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.597 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.786 Fsp3:   0.55
MCE-18:   38.0
?
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:   0.27 Fluc inhibitor:   0.264
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.993
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.11
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.079 Promiscuous compounds:   0.203

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.818 MDCK Permeability:   -4.664
Pgp-inhibitor:   0.0 Pgp-substrate:   0.079
PAMPA:   0.979
?
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%):   0.118 30% Bioavailability (F30%):   0.051
50% Bioavailability (F50%):   0.44

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.99
Plasma Protein Binding (PPB):   63.143% Volume Distribution (VD):   -0.147
Fu: 36.147%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.982
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.003
BSEP inhibitor:   0.381

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.189
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.025
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.394 CYP2D6-substrate:   0.879
CYP3A4-inhibitor:   0.074 CYP3A4-substrate:   0.994
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.09
HLM stability:   0.985
?
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):  10.133 Half-life (T1/2):  1.302

ADMET: Toxicity

hERG Blockers:  0.111 hERG Blockers (10um):  0.316
Human Hepatotoxicity (H-HT):  0.431 Drug-induced Liver Injury (DILI):  0.22
AMES Toxicity:  0.689 Rat Oral Acute Toxicity:  0.265
Maximum Recommended Daily Dose:  0.747 Skin Sensitization:  0.486
Carcinogencity:  0.613 Eye Corrosion:  0.0
Eye Irritation:  0.163 Respiratory Toxicity:  0.716
Drug-induced Neurotoxicity:  0.264 Ototoxicity:  0.712
Hematotoxicity:  0.197 Drug-induced Nephrotoxicity:  0.274
Genotoxicity:  0.828 RPMI-8226 Immunitoxicity:  0.057
A549 Cytotoxicity:  0.227 Hek293 Cytotoxicity:  0.511
BCF:   0.382
?
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:   3.061
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.604
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.736
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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
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC > 336700.0 nM PMID[32996318]
NPT2 Others Unspecified n.a. IC50 = 76000.0 nM PMID[32996318]

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 NPC479310 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
0.8246 Intermediate Similarity NPC479313
0.8 Intermediate Similarity NPC479311
0.7619 Intermediate Similarity NPC479308
0.7544 Intermediate Similarity NPC62366
0.6462 Remote Similarity NPC479312
0.6129 Remote Similarity NPC188380
0.6129 Remote Similarity NPC224543
0.597 Remote Similarity NPC479309
0.5781 Remote Similarity NPC213173
0.5625 Remote Similarity NPC185066
0.5556 Remote Similarity NPC80170
0.5385 Remote Similarity NPC33986
0.5373 Remote Similarity NPC168710
0.5312 Remote Similarity NPC96286
0.5303 Remote Similarity NPC279851
0.5231 Remote Similarity NPC50896
0.5231 Remote Similarity NPC326600
0.5143 Remote Similarity NPC26954
0.5143 Remote Similarity NPC38099
0.5135 Remote Similarity NPC485015
0.5077 Remote Similarity NPC55147
0.5072 Remote Similarity NPC153818
0.5072 Remote Similarity NPC232246
0.507 Remote Similarity NPC472525

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC479310 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