Natural Product: NPC59806

Natural Product IDNPC59806
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RFBNSYVWJNUVHE-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11810359
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0003520] Pyranoflavonoids

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 RFBNSYVWJNUVHE-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H18O6/c1-20(2)4-3-10-5-11(6-15(24)19(10)26-20)16-9-14(23)18-13(22)7-12(21)8-17(18)25-16/h3-8,16,21-22,24H,9H2,1-2H3
SMILES CC1(C)C=Cc2cc(cc(c2O1)O)C1CC(=O)c2c(cc(cc2O1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   354.11 Volume:   351.9
?
Van der Waals volume.
Dense:   1.006 LogP:   3.58
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.226
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.596
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   23.0
TPSA:   96.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.723 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.567 Fsp3:   0.25
MCE-18:   81.0
?
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:   1
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.755 Fluc inhibitor:   0.695
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.381
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.654
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.375 Promiscuous compounds:   0.03

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.026 MDCK Permeability:   -4.78
Pgp-inhibitor:   0.788 Pgp-substrate:   0.025
PAMPA:   0.281
?
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):   0.006
20% Bioavailability (F20%):   0.049 30% Bioavailability (F30%):   0.959
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.067 MRP1:   0.855
Plasma Protein Binding (PPB):   95.374% Volume Distribution (VD):   0.253
Fu: 5.028%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.975
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.986
BSEP inhibitor:   0.921

ADMET: Metabolism

CYP1A2-inhibitor:   0.493 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.274 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.779 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.997
CYP3A4-inhibitor:   0.092 CYP3A4-substrate:   0.998
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
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):  5.845 Half-life (T1/2):  1.111

ADMET: Toxicity

hERG Blockers:  0.108 hERG Blockers (10um):  0.57
Human Hepatotoxicity (H-HT):  0.6 Drug-induced Liver Injury (DILI):  0.542
AMES Toxicity:  0.758 Rat Oral Acute Toxicity:  0.713
Maximum Recommended Daily Dose:  0.817 Skin Sensitization:  0.67
Carcinogencity:  0.738 Eye Corrosion:  0.003
Eye Irritation:  0.97 Respiratory Toxicity:  0.931
Drug-induced Neurotoxicity:  0.273 Ototoxicity:  0.341
Hematotoxicity:  0.149 Drug-induced Nephrotoxicity:  0.336
Genotoxicity:  0.943 RPMI-8226 Immunitoxicity:  0.141
A549 Cytotoxicity:  0.492 Hek293 Cytotoxicity:  0.788
BCF:   1.673
?
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:   4.206
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.831
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.956
?
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
NPO24314 Erythrina sigmoidea Species Fabaceae Eukaryota n.a. bark n.a. PMID[14994185]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota stem bark n.a. n.a. PMID[17489632]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. stem n.a. PMID[18484536]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota stem bark Mukono, Uganda 2005-JUN PMID[19008110]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[19299148]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[19836230]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[20337486]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21116437]
NPO24314 Erythrina sigmoidea Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[7964799]
NPO24314 Erythrina sigmoidea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24314 Erythrina sigmoidea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24314 Erythrina sigmoidea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24314 Erythrina sigmoidea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8526 Erythrina abyssinica Species Fabaceae 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 NPC59806 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 NPC118256
0.8308 Intermediate Similarity NPC474038
0.7538 Intermediate Similarity NPC312973
0.7463 Intermediate Similarity NPC473272
0.6866 Remote Similarity NPC134783
0.6812 Remote Similarity NPC272502
0.6806 Remote Similarity NPC111786
0.6716 Remote Similarity NPC174953
0.6622 Remote Similarity NPC43319
0.6486 Remote Similarity NPC186686
0.6438 Remote Similarity NPC475784
0.6066 Remote Similarity NPC182421
0.5972 Remote Similarity NPC88964
0.5938 Remote Similarity NPC321011
0.5938 Remote Similarity NPC294852
0.5938 Remote Similarity NPC188679
0.5857 Remote Similarity NPC106976
0.5758 Remote Similarity NPC302950
0.5735 Remote Similarity NPC258630
0.5714 Remote Similarity NPC109223
0.5714 Remote Similarity NPC32441
0.5714 Remote Similarity NPC10937
0.5714 Remote Similarity NPC79943
0.5541 Remote Similarity NPC473990
0.5538 Remote Similarity NPC338131
0.5479 Remote Similarity NPC23728
0.5469 Remote Similarity NPC243083
0.5469 Remote Similarity NPC13768
0.5469 Remote Similarity NPC287246
0.5405 Remote Similarity NPC470890
0.5395 Remote Similarity NPC474021
0.5385 Remote Similarity NPC227579
0.5385 Remote Similarity NPC214166
0.5362 Remote Similarity NPC236637
0.5309 Remote Similarity NPC602605
0.5303 Remote Similarity NPC274784
0.5303 Remote Similarity NPC20709
0.5278 Remote Similarity NPC17170
0.52 Remote Similarity NPC200761
0.52 Remote Similarity NPC475790
0.5139 Remote Similarity NPC477841
0.5125 Remote Similarity NPC74924

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC59806 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
0.5758 Remote Similarity NPD1934 Phase 0
0.5714 Remote Similarity NPD1552 Clinical (unspecified phase)
0.5469 Remote Similarity NPD1550 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