Natural Product: NPC472646

Natural Product IDNPC472646
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 PJPNKQNHGYEFTE-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3581372
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 PJPNKQNHGYEFTE-UHFFFAOYSA-N
Standard InCHI InChI=1S/C32H28O6/c1-35-21-8-10-22-17(12-21)7-9-23-31(26(34)16-29(38-4)32(22)23)25-13-18-5-6-19-11-20(33)14-28(37-3)30(19)24(18)15-27(25)36-2/h7-16,33-34H,5-6H2,1-4H3
SMILES COc1ccc2c(c1)ccc1c2c(OC)cc(c1c1cc2CCc3c(c2cc1OC)c(OC)cc(c3)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   508.19 Volume:   529.157
?
Van der Waals volume.
Dense:   0.96 LogP:   4.893
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.113
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -7.494
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   32.0
TPSA:   77.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   6.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.252 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.804 Fsp3:   0.188
MCE-18:   71.579
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   1.0 Fluc inhibitor:   0.551
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.549
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.803
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.296 Promiscuous compounds:   0.176

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.909 MDCK Permeability:   -4.78
Pgp-inhibitor:   0.015 Pgp-substrate:   0.351
PAMPA:   0.082
?
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):   0.007
20% Bioavailability (F20%):   0.289 30% Bioavailability (F30%):   0.117
50% Bioavailability (F50%):   0.984

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.012 MRP1:   0.92
Plasma Protein Binding (PPB):   97.767% Volume Distribution (VD):   0.699
Fu: 1.245%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.988
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.614
BSEP inhibitor:   0.985

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   0.984
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.969
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.225
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.913
CYP3A4-inhibitor:   0.037 CYP3A4-substrate:   0.1
CYP2B6-substrate:   0.925 CYP2C8-inhibitor:   0.999
HLM stability:   0.998
?
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):  2.784 Half-life (T1/2):  1.075

ADMET: Toxicity

hERG Blockers:  0.778 hERG Blockers (10um):  0.774
Human Hepatotoxicity (H-HT):  0.808 Drug-induced Liver Injury (DILI):  0.953
AMES Toxicity:  0.935 Rat Oral Acute Toxicity:  0.696
Maximum Recommended Daily Dose:  0.977 Skin Sensitization:  0.141
Carcinogencity:  0.907 Eye Corrosion:  0.0
Eye Irritation:  0.112 Respiratory Toxicity:  0.987
Drug-induced Neurotoxicity:  0.933 Ototoxicity:  0.899
Hematotoxicity:  0.67 Drug-induced Nephrotoxicity:  0.913
Genotoxicity:  0.86 RPMI-8226 Immunitoxicity:  0.329
A549 Cytotoxicity:  0.932 Hek293 Cytotoxicity:  0.938
BCF:   1.708
?
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:   5.062
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.301
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.873
?
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 > 128.0 ug.mL-1 PMID[20405847]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC > 128.0 ug.mL-1 PMID[16309322]
NPT17 Organism Staphylococcus epidermidis Staphylococcus epidermidis MIC > 128.0 ug.mL-1 PMID[15715470]
NPT19 Organism Escherichia coli Escherichia coli MIC > 128.0 ug.mL-1 PMID[20405847]
NPT766 Organism Proteus vulgaris Proteus vulgaris MIC > 128.0 ug.mL-1 PMID[24417566]

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 NPC472646 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
0.7083 Intermediate Similarity NPC472649
0.6364 Remote Similarity NPC472648
0.5968 Remote Similarity NPC71465
0.5921 Remote Similarity NPC232525
0.5789 Remote Similarity NPC472647
0.5735 Remote Similarity NPC170328
0.5417 Remote Similarity NPC273623
0.5244 Remote Similarity NPC206525

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC472646 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