Natural Product: NPC479315

Natural Product IDNPC479315
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 XRGVPINPOSEDNY-ATTWWORZSA-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]
    • [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 XRGVPINPOSEDNY-ATTWWORZSA-N
Standard InCHI InChI=1S/C19H22O5/c1-14(5-4-11-19(2,3)24-21)10-12-22-16-8-6-15-7-9-18(20)23-17(15)13-16/h4,6-11,13,21H,5,12H2,1-3H3/b11-4+,14-10+
SMILES C/C(=CCOc1ccc2ccc(=O)oc2c1)/C/C=C/C(C)(C)OO

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   330.15 Volume:   345.563
?
Van der Waals volume.
Dense:   0.955 LogP:   3.695
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.476
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.384
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   14.0
TPSA:   68.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.354 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.045 Fsp3:   0.316
MCE-18:   14.0
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.626 Fluc inhibitor:   0.432
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.981
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.502
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.462 Promiscuous compounds:   0.124

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.969 MDCK Permeability:   -4.767
Pgp-inhibitor:   0.137 Pgp-substrate:   0.0
PAMPA:   0.123
?
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%):   0.729 30% Bioavailability (F30%):   0.482
50% Bioavailability (F50%):   0.347

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.999
Plasma Protein Binding (PPB):   95.494% Volume Distribution (VD):   0.072
Fu: 3.32%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.842 CYP1A2-substrate:   0.112
CYP2C19-inhibitor:   0.791 CYP2C19-substrate:   0.147
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.146
CYP3A4-inhibitor:   0.005 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.858 CYP2C8-inhibitor:   1.0
HLM stability:   0.928
?
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):  6.934 Half-life (T1/2):  0.612

ADMET: Toxicity

hERG Blockers:  0.314 hERG Blockers (10um):  0.419
Human Hepatotoxicity (H-HT):  0.686 Drug-induced Liver Injury (DILI):  0.98
AMES Toxicity:  0.844 Rat Oral Acute Toxicity:  0.452
Maximum Recommended Daily Dose:  0.68 Skin Sensitization:  0.726
Carcinogencity:  0.882 Eye Corrosion:  0.0
Eye Irritation:  0.103 Respiratory Toxicity:  0.468
Drug-induced Neurotoxicity:  0.262 Ototoxicity:  0.472
Hematotoxicity:  0.446 Drug-induced Nephrotoxicity:  0.244
Genotoxicity:  0.993 RPMI-8226 Immunitoxicity:  0.143
A549 Cytotoxicity:  0.07 Hek293 Cytotoxicity:  0.689
BCF:   1.342
?
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:   4.004
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.404
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.94
?
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]
NPO27785 Atalantia buxifolia Species Rutaceae Eukaryota Twigs n.a. n.a. PMID[29975532]
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]
NPO27785 Atalantia buxifolia Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27785 Atalantia buxifolia Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21771 Citrus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27785 Atalantia buxifolia Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27785 Atalantia buxifolia Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21771 Citrus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO27785 Atalantia buxifolia Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
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
NPT81 Cell line A549 Homo sapiens IC50 > 20.0 ug.mL-1 PMID[29975532]
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 > 20.0 ug.mL-1 PMID[29975532]
NPT65 Cell line HepG2 Homo sapiens IC50 > 20.0 ug.mL-1 PMID[29975532]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC > 387700.0 nM PMID[32996318]
NPT2 Others Unspecified n.a. IC50 = 19100.0 nM PMID[32996318]
NPT2 Others Unspecified n.a. FC > 2.0 n.a. 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 NPC479315 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
0.7937 Intermediate Similarity NPC601571
0.7619 Intermediate Similarity NPC33279
0.7581 Intermediate Similarity NPC479427
0.6866 Remote Similarity NPC479429
0.6866 Remote Similarity NPC479314
0.678 Remote Similarity NPC281356
0.6618 Remote Similarity NPC29734
0.6615 Remote Similarity NPC180006
0.6567 Remote Similarity NPC479428
0.6567 Remote Similarity NPC121740
0.6567 Remote Similarity NPC224774
0.6567 Remote Similarity NPC113098
0.6418 Remote Similarity NPC235190
0.6377 Remote Similarity NPC2363
0.625 Remote Similarity NPC601638
0.6027 Remote Similarity NPC267336
0.6027 Remote Similarity NPC272650
0.6 Remote Similarity NPC481285
0.5946 Remote Similarity NPC258567
0.5789 Remote Similarity NPC131198
0.5769 Remote Similarity NPC471068
0.5769 Remote Similarity NPC471069
0.5769 Remote Similarity NPC471070
0.5714 Remote Similarity NPC14697
0.561 Remote Similarity NPC471072
0.5432 Remote Similarity NPC469453
0.5412 Remote Similarity NPC471071
0.5366 Remote Similarity NPC469449
0.5254 Remote Similarity NPC265547
0.5062 Remote Similarity NPC318867
0.5062 Remote Similarity NPC146014

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC479315 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