Natural Product: NPC149875

Natural Product IDNPC149875
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RUCMCGSYMSEMIR-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 14585515
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002586] O-methylated isoflavonoids
          • [CHEMONTID:0002606] 4'-O-methylated isoflavonoids
            • [CHEMONTID:0002687] 4'-O-methylisoflavones

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 RUCMCGSYMSEMIR-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H20O4/c1-13(2)4-5-15-10-14(6-9-19(15)24-3)18-12-25-20-11-16(22)7-8-17(20)21(18)23/h4,6-12,22H,5H2,1-3H3
SMILES CC(=CCc1cc(ccc1OC)c1coc2cc(ccc2c1=O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   336.14 Volume:   357.536
?
Van der Waals volume.
Dense:   0.94 LogP:   4.087
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.618
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.939
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   59.67
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.703 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.435 Fsp3:   0.19
MCE-18:   18.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.943 Fluc inhibitor:   0.968
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.946
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.563
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.374 Promiscuous compounds:   0.063

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.67 MDCK Permeability:   -4.653
Pgp-inhibitor:   0.496 Pgp-substrate:   0.148
PAMPA:   0.199
?
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):   0.252
20% Bioavailability (F20%):   0.997 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.383
Plasma Protein Binding (PPB):   94.411% Volume Distribution (VD):   0.274
Fu: 4.461%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.569
OATP1B3 inhibitor:   0.904 BCRP inhibitor:   0.998
BSEP inhibitor:   0.725

ADMET: Metabolism

CYP1A2-inhibitor:   0.841 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.774 CYP2C19-substrate:   0.986
CYP2C9-inhibitor:   0.356 CYP2C9-substrate:   0.997
CYP2D6-inhibitor:   0.936 CYP2D6-substrate:   0.27
CYP3A4-inhibitor:   0.005 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.008 CYP2C8-inhibitor:   1.0
HLM stability:   0.939
?
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):  7.231 Half-life (T1/2):  0.872

ADMET: Toxicity

hERG Blockers:  0.252 hERG Blockers (10um):  0.611
Human Hepatotoxicity (H-HT):  0.603 Drug-induced Liver Injury (DILI):  0.723
AMES Toxicity:  0.679 Rat Oral Acute Toxicity:  0.754
Maximum Recommended Daily Dose:  0.823 Skin Sensitization:  0.409
Carcinogencity:  0.781 Eye Corrosion:  0.002
Eye Irritation:  0.855 Respiratory Toxicity:  0.849
Drug-induced Neurotoxicity:  0.627 Ototoxicity:  0.411
Hematotoxicity:  0.254 Drug-induced Nephrotoxicity:  0.425
Genotoxicity:  0.917 RPMI-8226 Immunitoxicity:  0.075
A549 Cytotoxicity:  0.272 Hek293 Cytotoxicity:  0.624
BCF:   1.856
?
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:   4.725
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.979
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.503
?
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
NPO20150 Erythrina sacleuxii Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[33170684]
NPO20150 Erythrina sacleuxii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20150 Erythrina sacleuxii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20150 Erythrina sacleuxii 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
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 20000.0 nM PMID[33170684]
NPT1117 Organism Salmonella enterica subsp. enterica Salmonella enterica subsp. enterica MIC > 190300.0 nM PMID[33170684]
NPT20 Organism Candida albicans Candida albicans MIC > 95100.0 nM PMID[33170684]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC > 154600.0 nM PMID[33170684]
NPT19 Organism Escherichia coli Escherichia coli MIC > 95100.0 nM PMID[33170684]

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 NPC149875 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 NPC233918
0.7042 Intermediate Similarity NPC7989
0.7015 Intermediate Similarity NPC215311
0.6825 Remote Similarity NPC209560
0.6825 Remote Similarity NPC490700
0.6615 Remote Similarity NPC12377
0.6528 Remote Similarity NPC104555
0.6515 Remote Similarity NPC80710
0.6438 Remote Similarity NPC104406
0.6438 Remote Similarity NPC285623
0.6351 Remote Similarity NPC223701
0.6351 Remote Similarity NPC472583
0.6143 Remote Similarity NPC161124
0.6061 Remote Similarity NPC203747
0.6061 Remote Similarity NPC609386
0.6029 Remote Similarity NPC139364
0.5974 Remote Similarity NPC123653
0.589 Remote Similarity NPC268059
0.5857 Remote Similarity NPC35544
0.5811 Remote Similarity NPC128774
0.5797 Remote Similarity NPC12175
0.5797 Remote Similarity NPC195763
0.5797 Remote Similarity NPC191741
0.5733 Remote Similarity NPC266572
0.5714 Remote Similarity NPC200060
0.5714 Remote Similarity NPC55162
0.5714 Remote Similarity NPC234560
0.5652 Remote Similarity NPC262623
0.5625 Remote Similarity NPC212767
0.5571 Remote Similarity NPC40290
0.5538 Remote Similarity NPC242893
0.551 Remote Similarity NPC76047
0.5467 Remote Similarity NPC611071
0.5405 Remote Similarity NPC213659
0.5405 Remote Similarity NPC326109
0.5352 Remote Similarity NPC156953
0.5333 Remote Similarity NPC219917
0.5333 Remote Similarity NPC40942
0.5294 Remote Similarity NPC487215
0.5278 Remote Similarity NPC291802
0.5224 Remote Similarity NPC235428
0.5205 Remote Similarity NPC478987
0.5195 Remote Similarity NPC166036
0.519 Remote Similarity NPC108859
0.5143 Remote Similarity NPC181124
0.5143 Remote Similarity NPC294409
0.5143 Remote Similarity NPC490701
0.5132 Remote Similarity NPC193564
0.5067 Remote Similarity NPC215375
0.5062 Remote Similarity NPC605730

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC149875 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