Natural Product: NPC480680

Natural Product IDNPC480680
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 XQBXANZIFQWJMH-NRNDYIJXSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 132576304
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003405] 2-arylbenzofuran flavonoids

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 XQBXANZIFQWJMH-NRNDYIJXSA-N
Standard InCHI InChI=1S/C30H26O6/c1-34-25-11-19(12-26(17-25)35-2)4-3-18-5-10-28-27(13-18)29(21-14-23(32)16-24(33)15-21)30(36-28)20-6-8-22(31)9-7-20/h3-17,29-33H,1-2H3/b4-3+/t29-,30+/m0/s1
SMILES COc1cc(/C=C/c2ccc3c(c2)[C@H](c2cc(cc(c2)O)O)[C@@H](c2ccc(cc2)O)O3)cc(c1)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   482.17 Volume:   503.121
?
Van der Waals volume.
Dense:   0.958 LogP:   5.557
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.554
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -6.755
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   29.0
TPSA:   88.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   5.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.281 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.425 Fsp3:   0.133
MCE-18:   87.294
?
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:   1.0 Fluc inhibitor:   0.997
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.231
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.961
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.604 Promiscuous compounds:   0.175

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.909 MDCK Permeability:   -4.814
Pgp-inhibitor:   0.047 Pgp-substrate:   0.008
PAMPA:   0.001
?
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%):   0.93 30% Bioavailability (F30%):   0.975
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.026
Plasma Protein Binding (PPB):   94.096% Volume Distribution (VD):   0.16
Fu: 7.417%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.934
BSEP inhibitor:   0.994

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.05
CYP2C19-inhibitor:   0.079 CYP2C19-substrate:   0.983
CYP2C9-inhibitor:   0.052 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.003 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.253
?
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):  7.559 Half-life (T1/2):  1.601

ADMET: Toxicity

hERG Blockers:  0.815 hERG Blockers (10um):  0.782
Human Hepatotoxicity (H-HT):  0.937 Drug-induced Liver Injury (DILI):  0.157
AMES Toxicity:  0.562 Rat Oral Acute Toxicity:  0.432
Maximum Recommended Daily Dose:  0.994 Skin Sensitization:  0.339
Carcinogencity:  0.224 Eye Corrosion:  0.0
Eye Irritation:  0.767 Respiratory Toxicity:  0.465
Drug-induced Neurotoxicity:  0.843 Ototoxicity:  0.724
Hematotoxicity:  0.038 Drug-induced Nephrotoxicity:  0.585
Genotoxicity:  0.998 RPMI-8226 Immunitoxicity:  0.117
A549 Cytotoxicity:  0.85 Hek293 Cytotoxicity:  0.988
BCF:   1.754
?
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:   4.738
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.869
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.311
?
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
NPO1086 Botrytis cinerea Species Sclerotiniaceae Eukaryota n.a. n.a. n.a. PMID[10691704]
NPO1086 Botrytis cinerea Species Sclerotiniaceae Eukaryota n.a. n.a. n.a. PMID[16378371]
NPO1086 Botrytis cinerea Species Sclerotiniaceae Eukaryota n.a. n.a. n.a. PMID[16643065]
NPO1086 Botrytis cinerea Species Sclerotiniaceae Eukaryota n.a. n.a. n.a. PMID[32705864]
NPO1086 Botrytis cinerea Species Sclerotiniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1086 Botrytis cinerea Species Sclerotiniaceae 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
NPT2257 Cell line MCF-10A Homo sapiens IC50 = 66000.0 nM PMID[32705864]
NPT65 Cell line HepG2 Homo sapiens IC50 = 27000.0 nM PMID[32705864]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 2000.0 nM PMID[32705864]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 22000.0 nM PMID[32705864]
NPT2 Others Unspecified n.a. Ratio = 32.0 n.a. PMID[32705864]

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 NPC480680 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
0.8667 High Similarity NPC480677
0.8621 High Similarity NPC480681
0.8103 Intermediate Similarity NPC125579
0.6571 Remote Similarity NPC112819
0.6571 Remote Similarity NPC133209
0.6571 Remote Similarity NPC6702
0.6094 Remote Similarity NPC175765
0.6087 Remote Similarity NPC478879
0.6087 Remote Similarity NPC478881
0.5909 Remote Similarity NPC141717
0.5735 Remote Similarity NPC480678
0.5714 Remote Similarity NPC59692
0.5571 Remote Similarity NPC478982
0.5362 Remote Similarity NPC76424
0.5362 Remote Similarity NPC15109
0.5362 Remote Similarity NPC291103
0.5362 Remote Similarity NPC11727
0.5286 Remote Similarity NPC480676
0.5068 Remote Similarity NPC149633

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC480680 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