Natural Product: NPC128774

Natural Product IDNPC128774
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ONLZHAOKMQJPIC-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5481243
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:0003651] 3'-hydroxy,4'-methoxyisoflavonoids

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 ONLZHAOKMQJPIC-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H20O6/c1-11(2)4-5-12-6-13(7-17(24)21(12)26-3)15-10-27-18-9-14(22)8-16(23)19(18)20(15)25/h4,6-10,22-24H,5H2,1-3H3
SMILES CC(=CCc1cc(cc(c1OC)O)c1coc2cc(cc(c2c1=O)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   368.13 Volume:   375.116
?
Van der Waals volume.
Dense:   0.981 LogP:   3.457
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.928
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.748
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   100.13
?
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
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.868 Fsp3:   0.19
MCE-18:   20.0
?
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:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.768 Fluc inhibitor:   0.567
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.95
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.63
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.321 Promiscuous compounds:   0.08

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.04 MDCK Permeability:   -4.821
Pgp-inhibitor:   0.039 Pgp-substrate:   0.241
PAMPA:   0.431
?
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):   0.017
20% Bioavailability (F20%):   0.982 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.616
Plasma Protein Binding (PPB):   95.022% Volume Distribution (VD):   -0.039
Fu: 4.123%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.807
OATP1B3 inhibitor:   0.909 BCRP inhibitor:   0.998
BSEP inhibitor:   0.133

ADMET: Metabolism

CYP1A2-inhibitor:   0.921 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.702 CYP2C19-substrate:   0.668
CYP2C9-inhibitor:   0.358 CYP2C9-substrate:   0.959
CYP2D6-inhibitor:   0.981 CYP2D6-substrate:   0.947
CYP3A4-inhibitor:   0.015 CYP3A4-substrate:   0.996
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
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):  3.171 Half-life (T1/2):  1.422

ADMET: Toxicity

hERG Blockers:  0.085 hERG Blockers (10um):  0.562
Human Hepatotoxicity (H-HT):  0.567 Drug-induced Liver Injury (DILI):  0.832
AMES Toxicity:  0.651 Rat Oral Acute Toxicity:  0.786
Maximum Recommended Daily Dose:  0.888 Skin Sensitization:  0.637
Carcinogencity:  0.641 Eye Corrosion:  0.0
Eye Irritation:  0.87 Respiratory Toxicity:  0.921
Drug-induced Neurotoxicity:  0.24 Ototoxicity:  0.347
Hematotoxicity:  0.119 Drug-induced Nephrotoxicity:  0.365
Genotoxicity:  0.988 RPMI-8226 Immunitoxicity:  0.092
A549 Cytotoxicity:  0.471 Hek293 Cytotoxicity:  0.698
BCF:   1.645
?
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:   4.493
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.695
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.234
?
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
NPO40124 Erythrina schliebenii Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[28112509]
NPO40124 Erythrina schliebenii Species 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
NPT82 Cell line MDA-MB-231 Homo sapiens EC50 = 77000.0 nM PMID[28112509]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis MIC = 86900.0 nM PMID[28112509]

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 NPC128774 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
0.7692 Intermediate Similarity NPC233918
0.7692 Intermediate Similarity NPC268059
0.7246 Intermediate Similarity NPC52889
0.7101 Intermediate Similarity NPC482075
0.697 Remote Similarity NPC238279
0.6615 Remote Similarity NPC194653
0.6615 Remote Similarity NPC481044
0.6389 Remote Similarity NPC74178
0.6377 Remote Similarity NPC213659
0.6377 Remote Similarity NPC326109
0.625 Remote Similarity NPC78341
0.6154 Remote Similarity NPC294409
0.6154 Remote Similarity NPC490701
0.6143 Remote Similarity NPC232947
0.6087 Remote Similarity NPC93552
0.6029 Remote Similarity NPC254702
0.597 Remote Similarity NPC200316
0.5915 Remote Similarity NPC85131
0.589 Remote Similarity NPC479305
0.589 Remote Similarity NPC485109
0.5821 Remote Similarity NPC19980
0.5821 Remote Similarity NPC239363
0.5811 Remote Similarity NPC149875
0.5806 Remote Similarity NPC193792
0.5797 Remote Similarity NPC45291
0.5735 Remote Similarity NPC309154
0.5696 Remote Similarity NPC303174
0.5676 Remote Similarity NPC166036
0.5625 Remote Similarity NPC278968
0.5616 Remote Similarity NPC40942
0.56 Remote Similarity NPC604255
0.5584 Remote Similarity NPC474960
0.5571 Remote Similarity NPC142876
0.5571 Remote Similarity NPC483637
0.5571 Remote Similarity NPC264550
0.5538 Remote Similarity NPC38065
0.5469 Remote Similarity NPC39426
0.5469 Remote Similarity NPC608554
0.5467 Remote Similarity NPC280937
0.5467 Remote Similarity NPC134287
0.5429 Remote Similarity NPC279668
0.5429 Remote Similarity NPC278323
0.5333 Remote Similarity NPC475705
0.5294 Remote Similarity NPC324447
0.5278 Remote Similarity NPC104728
0.5278 Remote Similarity NPC259166
0.527 Remote Similarity NPC203077
0.5205 Remote Similarity NPC158874
0.5205 Remote Similarity NPC20472
0.5205 Remote Similarity NPC241904
0.5205 Remote Similarity NPC167595
0.52 Remote Similarity NPC219917
0.5195 Remote Similarity NPC474052
0.5181 Remote Similarity NPC488441
0.5128 Remote Similarity NPC107838
0.5128 Remote Similarity NPC610891
0.5067 Remote Similarity NPC482708

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC128774 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
0.5469 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