Natural Product: NPC271288

Natural Product IDNPC271288
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Erythraddison Iii
IUPAC Name (3S)-5,7-dihydroxy-3-[4-methoxy-3-(3-methylbut-2-enyl)phenyl]-2,3-dihydrochromen-4-one
Synonyms erythraddison III
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2159047
PubChem CID 71454955
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0001612] Isoflavans
          • [CHEMONTID:0001827] Isoflavanones
            • [CHEMONTID:0003525] 3'-prenylated isoflavanones

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 MGSNGDMLFQANLV-MRXNPFEDSA-N
Standard InCHI InChI=1S/C21H22O5/c1-12(2)4-5-14-8-13(6-7-18(14)25-3)16-11-26-19-10-15(22)9-17(23)20(19)21(16)24/h4,6-10,16,22-23H,5,11H2,1-3H3/t16-/m1/s1
SMILES CC(=CCc1cc(ccc1OC)[C@H]1COc2cc(cc(c2C1=O)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   354.15 Volume:   368.962
?
Van der Waals volume.
Dense:   0.96 LogP:   4.523
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.568
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.239
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   75.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.813 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.185 Fsp3:   0.286
MCE-18:   59.815
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.694 Fluc inhibitor:   0.889
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.316
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.414
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.294 Promiscuous compounds:   0.152

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.962 MDCK Permeability:   -4.81
Pgp-inhibitor:   0.059 Pgp-substrate:   0.489
PAMPA:   0.44
?
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%):   0.911 30% Bioavailability (F30%):   0.945
50% Bioavailability (F50%):   0.981

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.009 MRP1:   0.828
Plasma Protein Binding (PPB):   96.066% Volume Distribution (VD):   0.354
Fu: 3.078%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.662
OATP1B3 inhibitor:   0.493 BCRP inhibitor:   0.992
BSEP inhibitor:   0.14

ADMET: Metabolism

CYP1A2-inhibitor:   0.935 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.98 CYP2C19-substrate:   0.974
CYP2C9-inhibitor:   0.356 CYP2C9-substrate:   0.875
CYP2D6-inhibitor:   0.921 CYP2D6-substrate:   0.973
CYP3A4-inhibitor:   0.055 CYP3A4-substrate:   1.0
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):  7.353 Half-life (T1/2):  0.951

ADMET: Toxicity

hERG Blockers:  0.122 hERG Blockers (10um):  0.58
Human Hepatotoxicity (H-HT):  0.715 Drug-induced Liver Injury (DILI):  0.596
AMES Toxicity:  0.787 Rat Oral Acute Toxicity:  0.793
Maximum Recommended Daily Dose:  0.678 Skin Sensitization:  0.767
Carcinogencity:  0.765 Eye Corrosion:  0.0
Eye Irritation:  0.645 Respiratory Toxicity:  0.85
Drug-induced Neurotoxicity:  0.403 Ototoxicity:  0.415
Hematotoxicity:  0.338 Drug-induced Nephrotoxicity:  0.603
Genotoxicity:  0.971 RPMI-8226 Immunitoxicity:  0.133
A549 Cytotoxicity:  0.508 Hek293 Cytotoxicity:  0.706
BCF:   2.067
?
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:   4.837
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.549
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.856
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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
NPO27387 Erythrina addisoniae Species Fabaceae Eukaryota Stems; Barks n.a. n.a. PMID[12828487]
NPO27387 Erythrina addisoniae Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[17517504]
NPO27387 Erythrina addisoniae Species Fabaceae Eukaryota Barks n.a. n.a. PMID[18302333]
NPO27387 Erythrina addisoniae Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[20934335]
NPO27387 Erythrina addisoniae Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[23022281]
NPO27387 Erythrina addisoniae Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27387 Erythrina addisoniae 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
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens IC50 = 4600.0 nM PMID[19344175]

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 IC50 = 6920.0 nM PMID[23891163]
NPT83 Cell line MCF7 Homo sapiens IC50 = 6840.0 nM PMID[15787459]
NPT2 Others Unspecified n.a. IC50 = 9220 nM PMID[19105653]

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 NPC271288 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
0.6724 Remote Similarity NPC260979
0.6607 Remote Similarity NPC316480
0.6094 Remote Similarity NPC482758
0.6061 Remote Similarity NPC189768
0.6061 Remote Similarity NPC120083
0.6 Remote Similarity NPC113770
0.5556 Remote Similarity NPC482076
0.5507 Remote Similarity NPC138205
0.5469 Remote Similarity NPC469584
0.5373 Remote Similarity NPC190817
0.5373 Remote Similarity NPC308200
0.5352 Remote Similarity NPC471115
0.5294 Remote Similarity NPC482763
0.5211 Remote Similarity NPC29777
0.5147 Remote Similarity NPC469575
0.5072 Remote Similarity NPC609848
0.507 Remote Similarity NPC482762
0.5068 Remote Similarity NPC471114

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC271288 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