Natural Product: NPC261435

Natural Product IDNPC261435
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RUSOQDVMBDLJIA-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 157649
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0002699] Benzodioxanes
        • [CHEMONTID:0002702] Benzo-1,4-dioxanes

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 RUSOQDVMBDLJIA-UHFFFAOYSA-N
Standard InCHI InChI=1S/C13H14O5/c1-7(2)11-13(14)18-12-9(16-4)5-8(15-3)6-10(12)17-11/h5-6H,1-4H3
SMILES CC(=C1C(=O)Oc2c(cc(cc2O1)OC)OC)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   250.08 Volume:   247.06
?
Van der Waals volume.
Dense:   1.012 LogP:   2.639
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.71
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.412
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   13.0
TPSA:   53.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.458 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.801 Fsp3:   0.308
MCE-18:   26.0
?
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:   0.028 Fluc inhibitor:   0.039
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.658
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.317
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.747 Promiscuous compounds:   0.133

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.563 MDCK Permeability:   -4.558
Pgp-inhibitor:   0.735 Pgp-substrate:   0.008
PAMPA:   0.064
?
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):   0.096
20% Bioavailability (F20%):   0.11 30% Bioavailability (F30%):   0.045
50% Bioavailability (F50%):   0.187

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.075 MRP1:   0.376
Plasma Protein Binding (PPB):   88.051% Volume Distribution (VD):   -0.064
Fu: 10.174%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.978
OATP1B3 inhibitor:   0.956 BCRP inhibitor:   0.01
BSEP inhibitor:   0.944

ADMET: Metabolism

CYP1A2-inhibitor:   0.98 CYP1A2-substrate:   0.892
CYP2C19-inhibitor:   0.965 CYP2C19-substrate:   0.747
CYP2C9-inhibitor:   0.551 CYP2C9-substrate:   0.165
CYP2D6-inhibitor:   0.038 CYP2D6-substrate:   0.873
CYP3A4-inhibitor:   0.064 CYP3A4-substrate:   0.002
CYP2B6-substrate:   0.241 CYP2C8-inhibitor:   0.111
HLM stability:   0.591
?
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):  7.915 Half-life (T1/2):  1.018

ADMET: Toxicity

hERG Blockers:  0.074 hERG Blockers (10um):  0.38
Human Hepatotoxicity (H-HT):  0.656 Drug-induced Liver Injury (DILI):  0.763
AMES Toxicity:  0.66 Rat Oral Acute Toxicity:  0.342
Maximum Recommended Daily Dose:  0.307 Skin Sensitization:  0.687
Carcinogencity:  0.886 Eye Corrosion:  0.635
Eye Irritation:  0.952 Respiratory Toxicity:  0.478
Drug-induced Neurotoxicity:  0.403 Ototoxicity:  0.26
Hematotoxicity:  0.752 Drug-induced Nephrotoxicity:  0.453
Genotoxicity:  0.485 RPMI-8226 Immunitoxicity:  0.115
A549 Cytotoxicity:  0.04 Hek293 Cytotoxicity:  0.213
BCF:   1.346
?
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:   3.703
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.588
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.241
?
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
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota Seeds Anhui province, China DOI[10.1016/j.foodres.2020.109416]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota Seeds Gansu province, China DOI[10.1016/j.foodres.2020.109416]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota Seeds Shanxi province, China DOI[10.1016/j.foodres.2020.109416]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota Seeds Shandong province, China DOI[10.1016/j.foodres.2020.109416]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota Seeds Henan province, China DOI[10.1016/j.foodres.2020.109416]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota n.a. root n.a. DOI[10.2174/092986712800229032]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota n.a. n.a. n.a. PMID[19402674]
NPO30226 Paeonia albiflora Species Paeoniaceae Eukaryota roots n.a. n.a. PMID[19691309]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota n.a. root n.a. PMID[19721258]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota n.a. root n.a. PMID[19772486]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota Roots n.a. n.a. PMID[20806783]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota n.a. root n.a. PMID[21782011]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota n.a. root n.a. PMID[22190295]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota n.a. seed n.a. PMID[23497864]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota n.a. root n.a. PMID[26838074]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota n.a. root n.a. PMID[27313650]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota n.a. root n.a. PMID[27429639]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota Roots n.a. n.a. PMID[29741372]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota Seeds HeZe, ShanDong, China early autumn (from August to the beginning of September PMID[32545196]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota Roots n.a. n.a. PMID[32951423]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota Seeds Xinjiang,China PMID[33063333]
NPO30851 Magnolia liliflora Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13730 Magnolia liliiflora Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30226 Paeonia albiflora Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24267 Paeonia veitchii Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21458 Radix paeoniae rubra Species Lymnaeidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7590 Agrostophyllum brevipes Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6103 Bjerkandera adusta Species Phanerochaetaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13558 Mundulea suberosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10631 Gerbera lanuginosa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24267 Paeonia veitchii Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30851 Magnolia liliflora Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30226 Paeonia albiflora Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4547 Hypericum aucheri Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23476 Paeonia lactiflora wild Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7590 Agrostophyllum brevipes Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4547 Hypericum aucheri Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21458 Radix paeoniae rubra Species Lymnaeidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24267 Paeonia veitchii Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13730 Magnolia liliiflora Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO30851 Magnolia liliflora Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24267 Paeonia veitchii Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO30226 Paeonia albiflora Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO4547 Hypericum aucheri Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6103 Bjerkandera adusta Species Phanerochaetaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13558 Mundulea suberosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1234 Plagiocheilus prostratus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10631 Gerbera lanuginosa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO414 Iostephane madrensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9798 Paeonia lactiflora Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7590 Agrostophyllum brevipes Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13730 Magnolia liliiflora Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24267 Paeonia veitchii Species Paeoniaceae 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

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 NPC261435 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
NPC

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC261435 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