Natural Product: NPC33554

Natural Product IDNPC33554
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 UVWJXGWUCHJBLP-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 44259959
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001615] Flavones
          • [CHEMONTID:0001136] Flavonols

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 UVWJXGWUCHJBLP-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H20O7/c1-11(2)8-9-27-13-6-4-12(5-7-13)19-18(25)17(24)16-14(22)10-15(23)20(26-3)21(16)28-19/h4-8,10,22-23,25H,9H2,1-3H3
SMILES CC(=CCOc1ccc(cc1)c1c(c(=O)c2c(cc(c(c2o1)OC)O)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   384.12 Volume:   383.906
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Van der Waals volume.
Dense:   1.001 LogP:   4.01
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.041
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.82
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   19.0
TPSA:   109.36
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Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.572 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.715 Fsp3:   0.19
MCE-18:   20.0
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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:   0.829 Fluc inhibitor:   0.469
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.889
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.725
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.228 Promiscuous compounds:   0.156

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.171 MDCK Permeability:   -4.772
Pgp-inhibitor:   0.776 Pgp-substrate:   0.16
PAMPA:   0.542
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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):   0.047
20% Bioavailability (F20%):   0.067 30% Bioavailability (F30%):   0.597
50% Bioavailability (F50%):   0.811

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.018 MRP1:   0.972
Plasma Protein Binding (PPB):   97.938% Volume Distribution (VD):   -0.654
Fu: 1.617%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.531
OATP1B3 inhibitor:   0.973 BCRP inhibitor:   0.957
BSEP inhibitor:   0.947

ADMET: Metabolism

CYP1A2-inhibitor:   0.631 CYP1A2-substrate:   0.905
CYP2C19-inhibitor:   0.07 CYP2C19-substrate:   0.723
CYP2C9-inhibitor:   0.936 CYP2C9-substrate:   0.006
CYP2D6-inhibitor:   0.925 CYP2D6-substrate:   0.19
CYP3A4-inhibitor:   0.026 CYP3A4-substrate:   0.219
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.997
?
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):  3.69 Half-life (T1/2):  1.589

ADMET: Toxicity

hERG Blockers:  0.115 hERG Blockers (10um):  0.537
Human Hepatotoxicity (H-HT):  0.475 Drug-induced Liver Injury (DILI):  0.844
AMES Toxicity:  0.56 Rat Oral Acute Toxicity:  0.375
Maximum Recommended Daily Dose:  0.395 Skin Sensitization:  0.581
Carcinogencity:  0.623 Eye Corrosion:  0.024
Eye Irritation:  0.928 Respiratory Toxicity:  0.837
Drug-induced Neurotoxicity:  0.074 Ototoxicity:  0.234
Hematotoxicity:  0.284 Drug-induced Nephrotoxicity:  0.179
Genotoxicity:  0.41 RPMI-8226 Immunitoxicity:  0.089
A549 Cytotoxicity:  0.309 Hek293 Cytotoxicity:  0.388
BCF:   1.426
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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:   4.5
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.408
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.127
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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
NPO28296 Dryopteris dickinsii Species Dryopteridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28277 Diospyros maingayi Species Ebenaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28296 Dryopteris dickinsii Species Dryopteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27887 Striga asiatica Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28242 Amomum latifolium Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28277 Diospyros maingayi Species Ebenaceae 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

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 NPC33554 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
0.8036 Intermediate Similarity NPC201451
0.625 Remote Similarity NPC610401
0.5938 Remote Similarity NPC86485
0.5797 Remote Similarity NPC273538
0.5781 Remote Similarity NPC241838
0.5625 Remote Similarity NPC600177
0.5507 Remote Similarity NPC607815
0.5385 Remote Similarity NPC44079
0.5147 Remote Similarity NPC54394
0.5075 Remote Similarity NPC301123

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC33554 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
0.5797 Remote Similarity NPD4378 Phase 3

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