Natural Product: NPC472649

Natural Product IDNPC472649
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 SPYPVTXQKIVDMJ-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3581375
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000025] Phenanthrenes and derivatives
        • [CHEMONTID:0003007] Phenanthrols

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 SPYPVTXQKIVDMJ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C31H26O6/c1-35-19-6-9-20-16(13-19)4-8-23-29(20)27(37-3)15-25(34)31(23)30-22-7-5-17-12-18(32)14-26(36-2)28(17)21(22)10-11-24(30)33/h4,6,8-15,32-34H,5,7H2,1-3H3
SMILES COc1ccc2c(c1)ccc1c2c(OC)cc(c1c1c(O)ccc2c1CCc1c2c(OC)cc(c1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   494.17 Volume:   511.861
?
Van der Waals volume.
Dense:   0.965 LogP:   4.72
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.872
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -6.752
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   32.0
TPSA:   88.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   6.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.245 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.833 Fsp3:   0.161
MCE-18:   71.778
?
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:   0.601
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.584
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.883
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.29 Promiscuous compounds:   0.11

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.994 MDCK Permeability:   -4.785
Pgp-inhibitor:   0.017 Pgp-substrate:   0.289
PAMPA:   0.225
?
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):   0.008
20% Bioavailability (F20%):   0.224 30% Bioavailability (F30%):   0.112
50% Bioavailability (F50%):   0.984

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.007 MRP1:   0.969
Plasma Protein Binding (PPB):   97.953% Volume Distribution (VD):   0.594
Fu: 1.322%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.971
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.457
BSEP inhibitor:   0.987

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.998 CYP2C19-substrate:   0.993
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.507
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.94
CYP3A4-inhibitor:   0.043 CYP3A4-substrate:   0.714
CYP2B6-substrate:   0.991 CYP2C8-inhibitor:   0.999
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):  5.573 Half-life (T1/2):  0.955

ADMET: Toxicity

hERG Blockers:  0.703 hERG Blockers (10um):  0.73
Human Hepatotoxicity (H-HT):  0.816 Drug-induced Liver Injury (DILI):  0.963
AMES Toxicity:  0.966 Rat Oral Acute Toxicity:  0.792
Maximum Recommended Daily Dose:  0.978 Skin Sensitization:  0.411
Carcinogencity:  0.943 Eye Corrosion:  0.0
Eye Irritation:  0.167 Respiratory Toxicity:  0.996
Drug-induced Neurotoxicity:  0.897 Ototoxicity:  0.902
Hematotoxicity:  0.661 Drug-induced Nephrotoxicity:  0.929
Genotoxicity:  0.898 RPMI-8226 Immunitoxicity:  0.355
A549 Cytotoxicity:  0.959 Hek293 Cytotoxicity:  0.954
BCF:   1.651
?
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:   5.146
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.165
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.799
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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
NPO10780 Bletilla striata Species Orchidaceae Eukaryota n.a. n.a. n.a. PMID[15686910]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota Fibrous Roots n.a. n.a. PMID[25760525]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota n.a. n.a. n.a. PMID[31415170]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO10780 Bletilla striata Species Orchidaceae 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
NPT1204 Organism Enterococcus faecalis ATCC 29212 Enterococcus faecalis ATCC 29212 MIC > 128.0 ug.mL-1 PMID[17438047]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC = 8.0 ug.mL-1 PMID[12617583]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 32.0 ug.mL-1 PMID[19179074]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 64.0 ug.mL-1 PubChem BioAssay data set
NPT17 Organism Staphylococcus epidermidis Staphylococcus epidermidis MIC = 8.0 ug.mL-1 PMID[17438047]
NPT19 Organism Escherichia coli Escherichia coli MIC > 128.0 ug.mL-1 PMID[23981532]
NPT766 Organism Proteus vulgaris Proteus vulgaris MIC > 128.0 ug.mL-1 PubChem BioAssay data set

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 NPC472649 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
0.8143 Intermediate Similarity NPC472648
0.7083 Intermediate Similarity NPC472646
0.6579 Remote Similarity NPC206525
0.5921 Remote Similarity NPC472647
0.5873 Remote Similarity NPC71465
0.5844 Remote Similarity NPC232525
0.5652 Remote Similarity NPC170328
0.5342 Remote Similarity NPC273623

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC472649 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