Natural Product: NPC115335

Natural Product IDNPC115335
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Erybreadin B
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL561967
PubChem CID 45268827
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002617] Furanoisoflavonoids
          • [CHEMONTID:0001608] Pterocarpans

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 XDRMVDDOBVPELW-CYFREDJKSA-N
Standard InCHI InChI=1S/C25H26O4/c1-14(2)5-6-16-20(26)9-7-18-22(16)27-13-19-15-8-10-21-17(23(15)28-24(18)19)11-12-25(3,4)29-21/h5,7-12,19,24,26H,6,13H2,1-4H3/t19-,24-/m0/s1
SMILES CC(=CCc1c(ccc2c1OC[C@H]1c3ccc4c(C=CC(C)(C)O4)c3O[C@@H]21)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   390.18 Volume:   412.243
?
Van der Waals volume.
Dense:   0.946 LogP:   5.247
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.999
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.901
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   26.0
TPSA:   47.92
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.669 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.046 Fsp3:   0.36
MCE-18:   93.824
?
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:   0.996 Fluc inhibitor:   0.75
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.92
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.551
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.296 Promiscuous compounds:   0.131

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.953 MDCK Permeability:   -4.657
Pgp-inhibitor:   0.407 Pgp-substrate:   0.263
PAMPA:   0.011
?
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):   0.0
20% Bioavailability (F20%):   0.99 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.088 MRP1:   0.914
Plasma Protein Binding (PPB):   95.25% Volume Distribution (VD):   0.444
Fu: 5.204%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.994
BSEP inhibitor:   0.947

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.997 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.215 CYP2C9-substrate:   0.011
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.284
CYP3A4-inhibitor:   0.648 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  5.148 Half-life (T1/2):  1.337

ADMET: Toxicity

hERG Blockers:  0.195 hERG Blockers (10um):  0.667
Human Hepatotoxicity (H-HT):  0.822 Drug-induced Liver Injury (DILI):  0.785
AMES Toxicity:  0.712 Rat Oral Acute Toxicity:  0.853
Maximum Recommended Daily Dose:  0.803 Skin Sensitization:  0.97
Carcinogencity:  0.462 Eye Corrosion:  0.0
Eye Irritation:  0.396 Respiratory Toxicity:  0.976
Drug-induced Neurotoxicity:  0.853 Ototoxicity:  0.85
Hematotoxicity:  0.442 Drug-induced Nephrotoxicity:  0.833
Genotoxicity:  0.653 RPMI-8226 Immunitoxicity:  0.09
A549 Cytotoxicity:  0.364 Hek293 Cytotoxicity:  0.685
BCF:   2.152
?
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:   5.158
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   7.143
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.561
?
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
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota stem bark n.a. n.a. PMID[17489632]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. stem n.a. PMID[18484536]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota stem bark Mukono, Uganda 2005-JUN PMID[19008110]
NPO13293 Lespedeza floribunda Species Fabaceae Eukaryota roots n.a. n.a. PMID[19132934]
NPO13293 Lespedeza floribunda Species Fabaceae Eukaryota n.a. root n.a. PMID[19132934]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[19299148]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[19836230]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[20337486]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21116437]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13293 Lespedeza floribunda Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO13293 Lespedeza floribunda Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8526 Erythrina abyssinica 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 = 4200.0 nM PMID[7595595]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT83 Cell line MCF7 Homo sapiens IC50 = 11800.0 nM PMID[17190440]
NPT83 Cell line MCF7 Homo sapiens IC50 = 6200.0 nM PMID[11325227]
NPT83 Cell line MCF7 Homo sapiens IC50 = 5600.0 nM PubChem BioAssay data set
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 = 7700.0 nM PMID[24613456]
NPT2 Others Unspecified n.a. IC50 = 2930.0 nM DrugMatrix in vitro pharmacology data

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 NPC115335 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
0.7297 Intermediate Similarity NPC198154
0.7077 Intermediate Similarity NPC129106
0.7067 Intermediate Similarity NPC604681
0.697 Remote Similarity NPC606249
0.6933 Remote Similarity NPC469557
0.6842 Remote Similarity NPC606185
0.6806 Remote Similarity NPC225696
0.6351 Remote Similarity NPC17343
0.6164 Remote Similarity NPC12875
0.6164 Remote Similarity NPC118114
0.6133 Remote Similarity NPC121925
0.6081 Remote Similarity NPC268917
0.6027 Remote Similarity NPC164574
0.5921 Remote Similarity NPC280092
0.5921 Remote Similarity NPC52947
0.5733 Remote Similarity NPC206224
0.5732 Remote Similarity NPC16269
0.5696 Remote Similarity NPC609291
0.56 Remote Similarity NPC196765
0.5556 Remote Similarity NPC244888
0.5488 Remote Similarity NPC97834
0.5432 Remote Similarity NPC482702
0.5357 Remote Similarity NPC80918
0.5357 Remote Similarity NPC21696
0.5357 Remote Similarity NPC160196
0.5325 Remote Similarity NPC129784
0.5316 Remote Similarity NPC610906
0.5256 Remote Similarity NPC228369
0.5256 Remote Similarity NPC300875
0.5181 Remote Similarity NPC13005
0.5116 Remote Similarity NPC188578
0.5062 Remote Similarity NPC39752
0.506 Remote Similarity NPC21776

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC115335 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