Natural Product: NPC541775

Natural Product IDNPC541775
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2'-Deoxypiscerythrone
IUPAC Name 5,7-dihydroxy-3-[4-hydroxy-3-methoxy-5-(3-methylbut-2-enyl)phenyl]chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 SWPGCQOSUJNESS-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H20O6/c1-11(2)4-5-12-6-13(7-18(26-3)20(12)24)15-10-27-17-9-14(22)8-16(23)19(17)21(15)25/h4,6-10,22-24H,5H2,1-3H3
SMILES COC1=CC(C2=COC3=CC(O)=CC(O)=C3C2=O)=CC(CC=C(C)C)=C1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   368.13 Volume:   375.116
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Van der Waals volume.
Dense:   0.981 LogP:   3.416
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.782
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.641
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   100.13
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.6 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.775 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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.674 Fluc inhibitor:   0.536
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.926
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.557
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.329 Promiscuous compounds:   0.087

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.116 MDCK Permeability:   -4.826
Pgp-inhibitor:   0.083 Pgp-substrate:   0.135
PAMPA:   0.55
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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):   0.103
20% Bioavailability (F20%):   0.981 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.683
Plasma Protein Binding (PPB):   96.358% Volume Distribution (VD):   -0.054
Fu: 3.036%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.788
OATP1B3 inhibitor:   0.982 BCRP inhibitor:   0.999
BSEP inhibitor:   0.371

ADMET: Metabolism

CYP1A2-inhibitor:   0.958 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.426 CYP2C19-substrate:   0.902
CYP2C9-inhibitor:   0.898 CYP2C9-substrate:   0.922
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.861
CYP3A4-inhibitor:   0.002 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.001 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):  6.32 Half-life (T1/2):  1.255

ADMET: Toxicity

hERG Blockers:  0.07 hERG Blockers (10um):  0.523
Human Hepatotoxicity (H-HT):  0.581 Drug-induced Liver Injury (DILI):  0.869
AMES Toxicity:  0.654 Rat Oral Acute Toxicity:  0.791
Maximum Recommended Daily Dose:  0.88 Skin Sensitization:  0.594
Carcinogencity:  0.693 Eye Corrosion:  0.0
Eye Irritation:  0.89 Respiratory Toxicity:  0.901
Drug-induced Neurotoxicity:  0.23 Ototoxicity:  0.317
Hematotoxicity:  0.147 Drug-induced Nephrotoxicity:  0.325
Genotoxicity:  0.99 RPMI-8226 Immunitoxicity:  0.095
A549 Cytotoxicity:  0.438 Hek293 Cytotoxicity:  0.684
BCF:   1.573
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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:   4.442
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.615
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.173
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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
NPO44819 Piscidia erythrina Genus Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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 NPC541775 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
0.7576 Intermediate Similarity NPC268059
0.7121 Intermediate Similarity NPC238279
0.7059 Intermediate Similarity NPC233918
0.7015 Intermediate Similarity NPC213659
0.7015 Intermediate Similarity NPC326109
0.6957 Remote Similarity NPC128774
0.6471 Remote Similarity NPC93552
0.6418 Remote Similarity NPC254702
0.6406 Remote Similarity NPC78341
0.6119 Remote Similarity NPC200316
0.6061 Remote Similarity NPC294409
0.6061 Remote Similarity NPC490701
0.6029 Remote Similarity NPC194653
0.6029 Remote Similarity NPC481044
0.6027 Remote Similarity NPC479305
0.597 Remote Similarity NPC19980
0.597 Remote Similarity NPC239363
0.5833 Remote Similarity NPC85131
0.5833 Remote Similarity NPC232947
0.5811 Remote Similarity NPC166036
0.5676 Remote Similarity NPC475705
0.5658 Remote Similarity NPC482075
0.5652 Remote Similarity NPC309154
0.5625 Remote Similarity NPC303174
0.56 Remote Similarity NPC280937
0.56 Remote Similarity NPC485109
0.5595 Remote Similarity NPC324447
0.5493 Remote Similarity NPC142876
0.5493 Remote Similarity NPC45291
0.5469 Remote Similarity NPC193792
0.5455 Remote Similarity NPC610891
0.5417 Remote Similarity NPC104728
0.5405 Remote Similarity NPC203077
0.5395 Remote Similarity NPC134287
0.5385 Remote Similarity NPC39426
0.5385 Remote Similarity NPC52889
0.5385 Remote Similarity NPC608554
0.5352 Remote Similarity NPC279668
0.5352 Remote Similarity NPC278323
0.5342 Remote Similarity NPC158874
0.5342 Remote Similarity NPC167595
0.5333 Remote Similarity NPC219917
0.5333 Remote Similarity NPC48624
0.5333 Remote Similarity NPC40942
0.5325 Remote Similarity NPC253822
0.5325 Remote Similarity NPC149875
0.5325 Remote Similarity NPC474052
0.5278 Remote Similarity NPC483637
0.5278 Remote Similarity NPC264550
0.5256 Remote Similarity NPC488567
0.5224 Remote Similarity NPC38065
0.52 Remote Similarity NPC215311
0.52 Remote Similarity NPC482708
0.5132 Remote Similarity NPC80962
0.5132 Remote Similarity NPC169162
0.5128 Remote Similarity NPC269285
0.5128 Remote Similarity NPC604255
0.5125 Remote Similarity NPC474960
0.5065 Remote Similarity NPC130589
0.5065 Remote Similarity NPC97255
0.5063 Remote Similarity NPC74178
0.5063 Remote Similarity NPC107838

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC541775 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
0.5385 Remote Similarity NPD1510 Phase 2

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