Natural Product: NPC113770

Natural Product IDNPC113770
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (3S)-Ferreirin
IUPAC Name (3S)-5,7-dihydroxy-3-(2-hydroxy-4-methoxyphenyl)-2,3-dihydrochromen-4-one
Synonyms (3S)-Ferreirin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL403383
PubChem CID 44446883
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

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 CBEPNYOFLRIAGR-LLVKDONJSA-N
Standard InCHI InChI=1S/C16H14O6/c1-21-9-2-3-10(12(18)6-9)11-7-22-14-5-8(17)4-13(19)15(14)16(11)20/h2-6,11,17-19H,7H2,1H3/t11-/m1/s1
SMILES COc1ccc([C@H]2COc3cc(cc(c3C2=O)O)O)c(c1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   302.08 Volume:   293.909
?
Van der Waals volume.
Dense:   1.028 LogP:   2.439
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.612
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.8
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   96.22
?
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:   0.787 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.023 Fsp3:   0.188
MCE-18:   57.789
?
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:   0.405 Fluc inhibitor:   0.966
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.249
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.365
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.349 Promiscuous compounds:   0.364

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.05 MDCK Permeability:   -4.827
Pgp-inhibitor:   0.016 Pgp-substrate:   0.423
PAMPA:   0.141
?
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):   0.001
20% Bioavailability (F20%):   0.213 30% Bioavailability (F30%):   0.352
50% Bioavailability (F50%):   0.842

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.028 MRP1:   0.774
Plasma Protein Binding (PPB):   95.173% Volume Distribution (VD):   -0.036
Fu: 4.815%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.923
OATP1B3 inhibitor:   0.92 BCRP inhibitor:   0.937
BSEP inhibitor:   0.254

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.413
CYP2C19-inhibitor:   0.375 CYP2C19-substrate:   0.059
CYP2C9-inhibitor:   0.945 CYP2C9-substrate:   0.037
CYP2D6-inhibitor:   0.444 CYP2D6-substrate:   0.961
CYP3A4-inhibitor:   0.011 CYP3A4-substrate:   0.114
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.441
HLM stability:   0.431
?
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):  6.903 Half-life (T1/2):  1.313

ADMET: Toxicity

hERG Blockers:  0.077 hERG Blockers (10um):  0.529
Human Hepatotoxicity (H-HT):  0.662 Drug-induced Liver Injury (DILI):  0.457
AMES Toxicity:  0.758 Rat Oral Acute Toxicity:  0.649
Maximum Recommended Daily Dose:  0.607 Skin Sensitization:  0.758
Carcinogencity:  0.729 Eye Corrosion:  0.021
Eye Irritation:  0.97 Respiratory Toxicity:  0.863
Drug-induced Neurotoxicity:  0.116 Ototoxicity:  0.197
Hematotoxicity:  0.162 Drug-induced Nephrotoxicity:  0.332
Genotoxicity:  0.926 RPMI-8226 Immunitoxicity:  0.159
A549 Cytotoxicity:  0.438 Hek293 Cytotoxicity:  0.754
BCF:   1.337
?
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:   3.896
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.163
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.313
?
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
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. Brazilian n.a. PMID[17950610]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. Brazilian n.a. PMID[18440233]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. n.a. n.a. PMID[26938776]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. n.a. n.a. PMID[32525315]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. 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
NPT461 Cell line PANC-1 Homo sapiens CD100 > 100.0 uM PMID[19721074]
NPT81 Cell line A549 Homo sapiens IC50 > 100000.0 nM DrugMatrix in vitro pharmacology data
NPT165 Cell line HeLa Homo sapiens IC50 > 100000.0 nM PubChem BioAssay data set
NPT453 Cell line HT-1080 Homo sapiens IC50 > 100000.0 nM Open TG-GATES in vivo data: Biochemistry
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 71300.0 nM PMID[18440233]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 100000.0 nM PMID[18440233]

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 NPC113770 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
0.6923 Remote Similarity NPC303185
0.6923 Remote Similarity NPC184649
0.6923 Remote Similarity NPC133501
0.6792 Remote Similarity NPC260979
0.6667 Remote Similarity NPC316480
0.6364 Remote Similarity NPC482076
0.6271 Remote Similarity NPC482763
0.625 Remote Similarity NPC469584
0.6 Remote Similarity NPC271288
0.5968 Remote Similarity NPC138205
0.5893 Remote Similarity NPC311144
0.5833 Remote Similarity NPC469575
0.5714 Remote Similarity NPC277032
0.5538 Remote Similarity NPC471115
0.5517 Remote Similarity NPC91236
0.5517 Remote Similarity NPC99333
0.5397 Remote Similarity NPC482703
0.5385 Remote Similarity NPC29777
0.5312 Remote Similarity NPC120083
0.5172 Remote Similarity NPC230479
0.5172 Remote Similarity NPC50315
0.5152 Remote Similarity NPC78247
0.5088 Remote Similarity NPC202981
0.5088 Remote Similarity NPC488571
0.5085 Remote Similarity NPC482955
0.5085 Remote Similarity NPC48204

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC113770 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