Natural Product: NPC483811

Natural Product IDNPC483811
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 NMVQTCAUGXWCNZ-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 14188386
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003646] 6-prenylated flavans
            • [CHEMONTID:0003507] 6-prenylated flavanones

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 NMVQTCAUGXWCNZ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C30H30O8/c1-14(2)10-11-18-27(35)20(12-19-25(33)15(3)26(34)23(16(4)31)29(19)37)30-24(28(18)36)21(32)13-22(38-30)17-8-6-5-7-9-17/h5-10,22,33-37H,11-13H2,1-4H3
SMILES CC(=CCc1c(c(Cc2c(c(C)c(c(C(=O)C)c2O)O)O)c2c(C(=O)CC(c3ccccc3)O2)c1O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   518.19 Volume:   531.894
?
Van der Waals volume.
Dense:   0.974 LogP:   4.486
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.296
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.217
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   26.0
TPSA:   144.52
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   5.0 Rings:   4.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.212 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.701 Fsp3:   0.267
MCE-18:   90.053
?
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:   Accepted BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.968 Fluc inhibitor:   0.586
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.69
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.853
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.303 Promiscuous compounds:   0.012

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.157 MDCK Permeability:   -4.791
Pgp-inhibitor:   0.979 Pgp-substrate:   0.0
PAMPA:   0.98
?
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):   0.172
20% Bioavailability (F20%):   0.095 30% Bioavailability (F30%):   0.868
50% Bioavailability (F50%):   0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.996
Plasma Protein Binding (PPB):   97.262% Volume Distribution (VD):   0.407
Fu: 2.879%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.111
BSEP inhibitor:   0.984

ADMET: Metabolism

CYP1A2-inhibitor:   0.211 CYP1A2-substrate:   0.894
CYP2C19-inhibitor:   0.068 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.054 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.454
CYP3A4-inhibitor:   0.966 CYP3A4-substrate:   0.568
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):  1.63 Half-life (T1/2):  1.408

ADMET: Toxicity

hERG Blockers:  0.037 hERG Blockers (10um):  0.588
Human Hepatotoxicity (H-HT):  0.806 Drug-induced Liver Injury (DILI):  0.333
AMES Toxicity:  0.67 Rat Oral Acute Toxicity:  0.707
Maximum Recommended Daily Dose:  0.592 Skin Sensitization:  0.959
Carcinogencity:  0.204 Eye Corrosion:  0.0
Eye Irritation:  0.669 Respiratory Toxicity:  0.976
Drug-induced Neurotoxicity:  0.075 Ototoxicity:  0.508
Hematotoxicity:  0.268 Drug-induced Nephrotoxicity:  0.717
Genotoxicity:  0.972 RPMI-8226 Immunitoxicity:  0.213
A549 Cytotoxicity:  0.818 Hek293 Cytotoxicity:  0.859
BCF:   1.469
?
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:   5.168
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.702
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.428
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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
NPO25967 Mallotus philippensis Species Euphorbiaceae Eukaryota n.a. fruit n.a. PMID[12499591]
NPO25967 Mallotus philippensis Species Euphorbiaceae Eukaryota n.a. fruit n.a. PMID[15516755]
NPO25967 Mallotus philippensis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[31318550]
NPO25967 Mallotus philippensis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25967 Mallotus philippensis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25967 Mallotus philippensis Species Euphorbiaceae 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
NPT878 Organism Streptococcus mutans Streptococcus mutans MIC = 30900.0 nM PMID[31318550]
NPT729 Organism Micrococcus luteus Micrococcus luteus MIC = 30900.0 nM PMID[31318550]
NPT566 Organism Salmonella typhimurium Salmonella enterica subsp. enterica serovar Typhimurium MIC > 100000.0 nM PMID[31318550]
NPT2909 Organism Shigella flexneri Shigella flexneri MIC > 100000.0 nM PMID[31318550]
NPT17 Organism Staphylococcus epidermidis Staphylococcus epidermidis MIC > 100000.0 nM PMID[31318550]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 61800.0 nM PMID[31318550]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MIC > 100000.0 nM PMID[31318550]
NPT19 Organism Escherichia coli Escherichia coli MIC = 30900.0 nM PMID[31318550]
NPT314 Organism Bacillus cereus Bacillus cereus MIC = 30900.0 nM PMID[31318550]

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 NPC483811 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
1.0 High Similarity NPC228779
0.6154 Remote Similarity NPC483809
0.6 Remote Similarity NPC1089
0.5694 Remote Similarity NPC95936
0.5694 Remote Similarity NPC265040
0.5488 Remote Similarity NPC483810
0.5479 Remote Similarity NPC122894
0.5417 Remote Similarity NPC76372
0.5417 Remote Similarity NPC37496
0.5405 Remote Similarity NPC610133
0.5373 Remote Similarity NPC248372
0.5325 Remote Similarity NPC473078
0.527 Remote Similarity NPC187282
0.527 Remote Similarity NPC250214
0.5263 Remote Similarity NPC608140
0.5217 Remote Similarity NPC110776
0.5143 Remote Similarity NPC215875

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC483811 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