Natural Product: NPC484043

Natural Product IDNPC484043
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 VPDYNOSDEMBDTC-UHFFFAOYSA-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 VPDYNOSDEMBDTC-UHFFFAOYSA-N
Standard InCHI InChI=1S/C25H24O5/c1-6-24(2,3)17-11-14(7-8-18(17)26)16-13-29-20-12-19-15(9-10-25(4,5)30-19)22(27)21(20)23(16)28/h6-13,26-27H,1H2,2-5H3
SMILES C=CC(C)(C)c1cc(ccc1O)c1coc2cc3c(C=CC(C)(C)O3)c(c2c1=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   404.16 Volume:   424.317
?
Van der Waals volume.
Dense:   0.952 LogP:   4.151
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.243
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.628
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   24.0
TPSA:   79.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.562 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.265 Fsp3:   0.24
MCE-18:   57.806
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.971 Fluc inhibitor:   0.409
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.628
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.828
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.365 Promiscuous compounds:   0.241

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.108 MDCK Permeability:   -4.757
Pgp-inhibitor:   0.811 Pgp-substrate:   0.001
PAMPA:   0.668
?
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):   0.02
20% Bioavailability (F20%):   0.998 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.876
Plasma Protein Binding (PPB):   97.784% Volume Distribution (VD):   0.068
Fu: 2.12%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.997
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.953 CYP1A2-substrate:   0.986
CYP2C19-inhibitor:   0.39 CYP2C19-substrate:   0.456
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.087
CYP2D6-inhibitor:   0.04 CYP2D6-substrate:   0.977
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.877 CYP2C8-inhibitor:   1.0
HLM stability:   0.689
?
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):  5.585 Half-life (T1/2):  0.823

ADMET: Toxicity

hERG Blockers:  0.139 hERG Blockers (10um):  0.646
Human Hepatotoxicity (H-HT):  0.4 Drug-induced Liver Injury (DILI):  0.704
AMES Toxicity:  0.403 Rat Oral Acute Toxicity:  0.758
Maximum Recommended Daily Dose:  0.896 Skin Sensitization:  0.622
Carcinogencity:  0.664 Eye Corrosion:  0.005
Eye Irritation:  0.929 Respiratory Toxicity:  0.929
Drug-induced Neurotoxicity:  0.425 Ototoxicity:  0.424
Hematotoxicity:  0.1 Drug-induced Nephrotoxicity:  0.258
Genotoxicity:  0.664 RPMI-8226 Immunitoxicity:  0.156
A549 Cytotoxicity:  0.543 Hek293 Cytotoxicity:  0.639
BCF:   1.842
?
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:   4.696
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.312
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.746
?
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
NPO40204 Millettia extensa Species Fabaceae Eukaryota Stems n.a. n.a. PMID[30106294]
NPO40204 Millettia extensa Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[31403786]

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 Activity = 61.1 % PMID[31403786]
NPT729 Organism Micrococcus luteus Micrococcus luteus MIC = 64.0 ug.mL-1 PMID[31403786]
NPT878 Organism Streptococcus mutans Streptococcus mutans MIC = 128.0 ug.mL-1 PMID[31403786]
NPT566 Organism Salmonella typhimurium Salmonella enterica subsp. enterica serovar Typhimurium MIC = 128.0 ug.mL-1 PMID[31403786]
NPT2909 Organism Shigella flexneri Shigella flexneri MIC = 128.0 ug.mL-1 PMID[31403786]
NPT17 Organism Staphylococcus epidermidis Staphylococcus epidermidis MIC = 128.0 ug.mL-1 PMID[31403786]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 64.0 ug.mL-1 PMID[31403786]
NPT314 Organism Bacillus cereus Bacillus cereus MIC = 64.0 ug.mL-1 PMID[31403786]

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 NPC484043 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
0.7879 Intermediate Similarity NPC97716
0.6892 Remote Similarity NPC184755
0.6849 Remote Similarity NPC84124
0.6711 Remote Similarity NPC233502
0.6622 Remote Similarity NPC184547
0.5976 Remote Similarity NPC113475
0.5775 Remote Similarity NPC473076
0.5714 Remote Similarity NPC484041
0.5595 Remote Similarity NPC302762
0.5375 Remote Similarity NPC107838
0.5375 Remote Similarity NPC303197
0.5357 Remote Similarity NPC484048
0.5316 Remote Similarity NPC6511
0.5256 Remote Similarity NPC219917
0.525 Remote Similarity NPC474052
0.519 Remote Similarity NPC168085
0.5185 Remote Similarity NPC231763
0.5185 Remote Similarity NPC237635
0.5176 Remote Similarity NPC238064
0.5128 Remote Similarity NPC166054
0.5128 Remote Similarity NPC24673
0.5128 Remote Similarity NPC265932
0.5122 Remote Similarity NPC104406
0.5122 Remote Similarity NPC178964
0.506 Remote Similarity NPC170026

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC484043 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