Natural Product: NPC309154

Natural Product IDNPC309154
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Theralin
IUPAC Name 5,7-dihydroxy-3-(4-hydroxy-2-methoxyphenyl)chromen-4-one
Synonyms Theralin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL7348
PubChem CID 44264432
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002901] Isoflav-2-enes
          • [CHEMONTID:0000494] Isoflavones

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 JNJLRXUXPJHPCK-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H12O6/c1-21-13-5-8(17)2-3-10(13)11-7-22-14-6-9(18)4-12(19)15(14)16(11)20/h2-7,17-19H,1H3
SMILES COc1cc(O)ccc1c1coc2c(c1=O)c(O)cc(c2)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.06 Volume:   291.273
?
Van der Waals volume.
Dense:   1.03 LogP:   1.792
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.934
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.041
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
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:   0.672 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.452 Fsp3:   0.062
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:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.43 Fluc inhibitor:   0.78
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.801
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.56
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.489 Promiscuous compounds:   0.861

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.979 MDCK Permeability:   -4.821
Pgp-inhibitor:   0.002 Pgp-substrate:   0.353
PAMPA:   0.498
?
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):   0.002
20% Bioavailability (F20%):   0.205 30% Bioavailability (F30%):   0.513
50% Bioavailability (F50%):   0.978

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.061 MRP1:   0.58
Plasma Protein Binding (PPB):   94.883% Volume Distribution (VD):   -0.304
Fu: 7.346%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.844
OATP1B3 inhibitor:   0.93 BCRP inhibitor:   0.885
BSEP inhibitor:   0.28

ADMET: Metabolism

CYP1A2-inhibitor:   0.996 CYP1A2-substrate:   0.916
CYP2C19-inhibitor:   0.006 CYP2C19-substrate:   0.35
CYP2C9-inhibitor:   0.949 CYP2C9-substrate:   0.992
CYP2D6-inhibitor:   0.998 CYP2D6-substrate:   0.992
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.868
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.915
HLM stability:   0.626
?
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):  5.833 Half-life (T1/2):  1.372

ADMET: Toxicity

hERG Blockers:  0.135 hERG Blockers (10um):  0.534
Human Hepatotoxicity (H-HT):  0.457 Drug-induced Liver Injury (DILI):  0.71
AMES Toxicity:  0.641 Rat Oral Acute Toxicity:  0.544
Maximum Recommended Daily Dose:  0.87 Skin Sensitization:  0.49
Carcinogencity:  0.803 Eye Corrosion:  0.082
Eye Irritation:  0.995 Respiratory Toxicity:  0.82
Drug-induced Neurotoxicity:  0.151 Ototoxicity:  0.148
Hematotoxicity:  0.07 Drug-induced Nephrotoxicity:  0.075
Genotoxicity:  0.965 RPMI-8226 Immunitoxicity:  0.069
A549 Cytotoxicity:  0.264 Hek293 Cytotoxicity:  0.738
BCF:   1.215
?
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:   3.721
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.384
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.915
?
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
NPO9646 Crotalaria pallida Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[12662101]
NPO9646 Crotalaria pallida Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[15013012]
NPO10262 Crotalaria assamica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[15013012]
NPO14114 Dalbergia parviflora Species Fabaceae Eukaryota heartwood n.a. n.a. PMID[19928832]
NPO9646 Crotalaria pallida Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14114 Dalbergia parviflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10262 Crotalaria assamica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10262 Crotalaria assamica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9646 Crotalaria pallida Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10262 Crotalaria assamica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9646 Crotalaria pallida Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14114 Dalbergia parviflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10262 Crotalaria assamica 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
NPT3102 Individual protein Beta-glucuronidase Rattus norvegicus IC50 > 30000.0 nM DrugMatrix in vivo data: Pathology
NPT3103 Individual protein Lysozyme C Rattus norvegicus IC50 > 30000.0 nM PMID[16309323]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT396 Cell line T47D Homo sapiens Activity > 100.0 uM PMID[12061876]
NPT83 Cell line MCF7 Homo sapiens Activity = 0.4 uM PMID[12061876]
NPT83 Cell line MCF7 Homo sapiens Activity = 0.01 uM PMID[12061876]
NPT396 Cell line T47D Homo sapiens Activity = 1.7 uM PMID[12061876]
NPT83 Cell line MCF7 Homo sapiens Activity > 100.0 uM PMID[10999467]
NPT83 Cell line MCF7 Homo sapiens Activity = 0.6 uM PMID[9873604]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus IC50 > 30000.0 nM PMID[9358636]
NPT29 Organism Rattus norvegicus Rattus norvegicus IC50 > 30000.0 nM PMID[16309323]





 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 NPC309154 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
0.7636 Intermediate Similarity NPC19980
0.7544 Intermediate Similarity NPC483637
0.7368 Intermediate Similarity NPC278323
0.7018 Intermediate Similarity NPC239363
0.6949 Remote Similarity NPC142876
0.6842 Remote Similarity NPC294409
0.6842 Remote Similarity NPC490701
0.678 Remote Similarity NPC279668
0.6667 Remote Similarity NPC254702
0.6667 Remote Similarity NPC264550
0.6667 Remote Similarity NPC78341
0.6667 Remote Similarity NPC39426
0.661 Remote Similarity NPC200316
0.65 Remote Similarity NPC194653
0.6452 Remote Similarity NPC167595
0.6429 Remote Similarity NPC87545
0.6393 Remote Similarity NPC45291
0.6269 Remote Similarity NPC303197
0.623 Remote Similarity NPC481044
0.6212 Remote Similarity NPC280937
0.614 Remote Similarity NPC38065
0.6071 Remote Similarity NPC608554
0.6061 Remote Similarity NPC233918
0.597 Remote Similarity NPC479305
0.5893 Remote Similarity NPC193792
0.5821 Remote Similarity NPC268059
0.5781 Remote Similarity NPC104728
0.5738 Remote Similarity NPC303644
0.5735 Remote Similarity NPC128774
0.5714 Remote Similarity NPC90665
0.5692 Remote Similarity NPC471289
0.5634 Remote Similarity NPC474960
0.5574 Remote Similarity NPC131266
0.5574 Remote Similarity NPC269451
0.5571 Remote Similarity NPC482075
0.5522 Remote Similarity NPC213659
0.5522 Remote Similarity NPC85131
0.5522 Remote Similarity NPC326109
0.5522 Remote Similarity NPC232947
0.5429 Remote Similarity NPC474052
0.5397 Remote Similarity NPC605826
0.5385 Remote Similarity NPC101366
0.5385 Remote Similarity NPC55162
0.5385 Remote Similarity NPC476055
0.5373 Remote Similarity NPC608523
0.5362 Remote Similarity NPC475705
0.5352 Remote Similarity NPC231763
0.5352 Remote Similarity NPC107838
0.5323 Remote Similarity NPC7013
0.5312 Remote Similarity NPC121527
0.5278 Remote Similarity NPC52889
0.5224 Remote Similarity NPC93552
0.5147 Remote Similarity NPC238279
0.5139 Remote Similarity NPC74178
0.5079 Remote Similarity NPC116632
0.5077 Remote Similarity NPC262623
0.507 Remote Similarity NPC134287
0.507 Remote Similarity NPC485109

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC309154 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
0.6667 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