Natural Product: NPC479156

Natural Product IDNPC479156
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 MFSYWYMQJVDTEK-CXUHLZMHSA-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 MFSYWYMQJVDTEK-CXUHLZMHSA-N
Standard InCHI InChI=1S/C28H30O6/c1-15(2)7-8-16(3)9-10-18-23-22(14-20(30)26(18)32-6)33-27-17-11-12-28(4,5)34-21(17)13-19(29)24(27)25(23)31/h7,9,11-14,29-30H,8,10H2,1-6H3/b16-9+
SMILES CC(=CC/C(=C/Cc1c2c(cc(c1OC)O)oc1c3C=CC(C)(C)Oc3cc(c1c2=O)O)/C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   462.2 Volume:   484.995
?
Van der Waals volume.
Dense:   0.953 LogP:   7.338
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.911
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.374
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   24.0
TPSA:   89.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.337 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.54 Fsp3:   0.321
MCE-18:   57.514
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.994 Fluc inhibitor:   0.412
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.932
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.906
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.218 Promiscuous compounds:   0.212

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.032 MDCK Permeability:   -4.664
Pgp-inhibitor:   0.995 Pgp-substrate:   0.108
PAMPA:   0.023
?
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):   0.007
20% Bioavailability (F20%):   0.96 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.919
Plasma Protein Binding (PPB):   96.775% Volume Distribution (VD):   0.181
Fu: 2.888%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.982 BCRP inhibitor:   0.989
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.202 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   0.998 CYP2C19-substrate:   0.92
CYP2C9-inhibitor:   0.877 CYP2C9-substrate:   0.671
CYP2D6-inhibitor:   0.759 CYP2D6-substrate:   0.11
CYP3A4-inhibitor:   0.102 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  2.961 Half-life (T1/2):  1.36

ADMET: Toxicity

hERG Blockers:  0.095 hERG Blockers (10um):  0.633
Human Hepatotoxicity (H-HT):  0.68 Drug-induced Liver Injury (DILI):  0.972
AMES Toxicity:  0.403 Rat Oral Acute Toxicity:  0.746
Maximum Recommended Daily Dose:  0.708 Skin Sensitization:  0.955
Carcinogencity:  0.76 Eye Corrosion:  0.0
Eye Irritation:  0.506 Respiratory Toxicity:  0.96
Drug-induced Neurotoxicity:  0.065 Ototoxicity:  0.36
Hematotoxicity:  0.308 Drug-induced Nephrotoxicity:  0.175
Genotoxicity:  0.907 RPMI-8226 Immunitoxicity:  0.116
A549 Cytotoxicity:  0.369 Hek293 Cytotoxicity:  0.586
BCF:   2.306
?
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:   5.239
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   7.353
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.719
?
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
NPO40853 Garcinia tetrandra Species Clusiaceae Eukaryota Stem Bark n.a. n.a. PMID[30978023]
NPO40853 Garcinia tetrandra Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT83 Cell line MCF7 Homo sapiens IC50 > 10000.0 nM PMID[30978023]
NPT91 Cell line KB Homo sapiens IC50 > 10000.0 nM PMID[30978023]
NPT65 Cell line HepG2 Homo sapiens IC50 > 10000.0 nM PMID[30978023]
NPT139 Cell line HT-29 Homo sapiens IC50 > 10000.0 nM PMID[30978023]
NPT20987 Cell line HeLa S3 Homo sapiens IC50 > 10000.0 nM PMID[30978023]

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 NPC479156 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
0.7848 Intermediate Similarity NPC479157
0.6437 Remote Similarity NPC39091
0.6341 Remote Similarity NPC275780
0.6071 Remote Similarity NPC95842
0.5882 Remote Similarity NPC482612
0.5682 Remote Similarity NPC206153
0.5682 Remote Similarity NPC271629
0.561 Remote Similarity NPC55662
0.561 Remote Similarity NPC479160
0.5568 Remote Similarity NPC482611
0.5568 Remote Similarity NPC472402
0.5476 Remote Similarity NPC220313
0.5465 Remote Similarity NPC38219
0.5402 Remote Similarity NPC300727
0.5281 Remote Similarity NPC239752
0.5275 Remote Similarity NPC479155
0.5244 Remote Similarity NPC241904
0.5238 Remote Similarity NPC120105
0.5227 Remote Similarity NPC236521
0.5181 Remote Similarity NPC14353
0.5111 Remote Similarity NPC40491
0.5111 Remote Similarity NPC481615
0.5111 Remote Similarity NPC278052
0.5106 Remote Similarity NPC472449
0.5056 Remote Similarity NPC329760
0.5053 Remote Similarity NPC479158

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC479156 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