Natural Product: NPC480479

Natural Product IDNPC480479
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 BVFKMONTRIVXBO-OLZOCXBDSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 46861795
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0000369] Diphenylmethanes

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 BVFKMONTRIVXBO-OLZOCXBDSA-N
Standard InCHI InChI=1S/C20H26O5/c1-12(11-21)13(2)20(14-5-7-16(22)18(9-14)24-3)15-6-8-17(23)19(10-15)25-4/h5-10,12-13,20-23H,11H2,1-4H3/t12-,13+/m1/s1
SMILES C[C@H](CO)[C@H](C)C(c1ccc(c(c1)OC)O)c1ccc(c(c1)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   346.18 Volume:   365.496
?
Van der Waals volume.
Dense:   0.947 LogP:   3.085
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.809
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.706
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   12.0
TPSA:   79.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.715 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.213 Fsp3:   0.4
MCE-18:   30.0
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.237 Fluc inhibitor:   0.006
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.072
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.07
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.307 Promiscuous compounds:   0.224

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.055 MDCK Permeability:   -4.772
Pgp-inhibitor:   0.081 Pgp-substrate:   0.116
PAMPA:   0.002
?
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%):   0.103 30% Bioavailability (F30%):   0.123
50% Bioavailability (F50%):   0.952

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.008 MRP1:   0.964
Plasma Protein Binding (PPB):   91.336% Volume Distribution (VD):   -0.086
Fu: 7.627%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.279
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.002
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.998
CYP2C9-inhibitor:   0.514 CYP2C9-substrate:   0.96
CYP2D6-inhibitor:   0.404 CYP2D6-substrate:   0.999
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.062
?
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):  9.483 Half-life (T1/2):  1.663

ADMET: Toxicity

hERG Blockers:  0.07 hERG Blockers (10um):  0.442
Human Hepatotoxicity (H-HT):  0.716 Drug-induced Liver Injury (DILI):  0.307
AMES Toxicity:  0.445 Rat Oral Acute Toxicity:  0.208
Maximum Recommended Daily Dose:  0.165 Skin Sensitization:  0.898
Carcinogencity:  0.341 Eye Corrosion:  0.057
Eye Irritation:  0.932 Respiratory Toxicity:  0.537
Drug-induced Neurotoxicity:  0.398 Ototoxicity:  0.747
Hematotoxicity:  0.396 Drug-induced Nephrotoxicity:  0.642
Genotoxicity:  0.193 RPMI-8226 Immunitoxicity:  0.134
A549 Cytotoxicity:  0.323 Hek293 Cytotoxicity:  0.438
BCF:   0.909
?
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:   3.42
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.711
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.02
?
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
NPO8247 Austrobaileya scandens Species Austrobaileyaceae Eukaryota n.a. n.a. n.a. PMID[27214307]
NPO8247 Austrobaileya scandens Species Austrobaileyaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8247 Austrobaileya scandens Species Austrobaileyaceae 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
NPT165 Cell line HeLa Homo sapiens IC50 > 100000.0 nM PMID[25124113]
NPT165 Cell line HeLa Homo sapiens GI = 7.0 % PMID[25124113]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. GI = 0.0 % PMID[25124113]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 100000.0 nM PMID[25124113]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 6363.0 nM PMID[27214307]

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 NPC480479 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
0.75 Intermediate Similarity NPC280704
0.619 Remote Similarity NPC474040
0.6 Remote Similarity NPC277458
0.6 Remote Similarity NPC307050
0.5918 Remote Similarity NPC266705
0.5918 Remote Similarity NPC29008
0.5769 Remote Similarity NPC184613
0.5769 Remote Similarity NPC311256
0.5686 Remote Similarity NPC169214
0.5686 Remote Similarity NPC192597
0.5686 Remote Similarity NPC176030
0.5686 Remote Similarity NPC313081
0.5455 Remote Similarity NPC82336
0.5455 Remote Similarity NPC85488
0.5455 Remote Similarity NPC476343
0.5455 Remote Similarity NPC602071
0.5385 Remote Similarity NPC9067
0.537 Remote Similarity NPC227002
0.5357 Remote Similarity NPC78987
0.5319 Remote Similarity NPC487676
0.5128 Remote Similarity NPC7097
0.5122 Remote Similarity NPC156840
0.5116 Remote Similarity NPC160380
0.5116 Remote Similarity NPC320987
0.5116 Remote Similarity NPC38996
0.5116 Remote Similarity NPC221049
0.5106 Remote Similarity NPC242807
0.5106 Remote Similarity NPC153739

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC480479 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