Natural Product: NPC114268

Natural Product IDNPC114268
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 OSJKAGRXDVEZQO-SSDOTTSWSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 91617751
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000086] Pyrans
        • [CHEMONTID:0000481] Pyranones and derivatives
          • [CHEMONTID:0001211] Dihydropyranones

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 OSJKAGRXDVEZQO-SSDOTTSWSA-N
Standard InCHI InChI=1S/C15H16O5/c1-7-11-9(6-10(16)19-7)8-4-5-15(2,3)20-14(8)13(18)12(11)17/h6-7,17H,4-5H2,1-3H3/t7-/m1/s1
SMILES C[C@@H]1C2=C(C(=O)C3=C(CCC(C)(C)O3)C2=CC(=O)O1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   276.1 Volume:   273.096
?
Van der Waals volume.
Dense:   1.011 LogP:   1.279
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.535
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.021
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The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   18.0
TPSA:   72.83
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.686 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.074 Fsp3:   0.467
MCE-18:   47.273
?
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:   0.078 Fluc inhibitor:   0.328
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.835
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.388
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.599 Promiscuous compounds:   0.099

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.887 MDCK Permeability:   -4.704
Pgp-inhibitor:   0.942 Pgp-substrate:   0.019
PAMPA:   0.46
?
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):   0.222
20% Bioavailability (F20%):   0.895 30% Bioavailability (F30%):   0.994
50% Bioavailability (F50%):   0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.013 MRP1:   0.952
Plasma Protein Binding (PPB):   97.375% Volume Distribution (VD):   -0.262
Fu: 2.566%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.984 BCRP inhibitor:   0.044
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.781 CYP1A2-substrate:   0.988
CYP2C19-inhibitor:   0.989 CYP2C19-substrate:   0.976
CYP2C9-inhibitor:   0.165 CYP2C9-substrate:   0.223
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.825
CYP3A4-inhibitor:   0.997 CYP3A4-substrate:   0.998
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.994
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):  2.236 Half-life (T1/2):  1.754

ADMET: Toxicity

hERG Blockers:  0.023 hERG Blockers (10um):  0.159
Human Hepatotoxicity (H-HT):  0.721 Drug-induced Liver Injury (DILI):  0.874
AMES Toxicity:  0.61 Rat Oral Acute Toxicity:  0.316
Maximum Recommended Daily Dose:  0.547 Skin Sensitization:  0.951
Carcinogencity:  0.756 Eye Corrosion:  0.047
Eye Irritation:  0.908 Respiratory Toxicity:  0.48
Drug-induced Neurotoxicity:  0.493 Ototoxicity:  0.429
Hematotoxicity:  0.641 Drug-induced Nephrotoxicity:  0.906
Genotoxicity:  0.786 RPMI-8226 Immunitoxicity:  0.152
A549 Cytotoxicity:  0.064 Hek293 Cytotoxicity:  0.096
BCF:   1.541
?
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:   4.112
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.958
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.323
?
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
NPO17090 Epipedobates tricolor Species Dendrobatidae Eukaryota n.a. n.a. n.a. PMID[14575435]
NPO14446 Selaginella doederleinii Species Selaginellaceae Eukaryota n.a. whole plant n.a. PMID[18758121]
NPO15373 Actaea dahurica Species Ranunculaceae Eukaryota Roots n.a. n.a. PMID[28558206]
NPO15373 Actaea dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. PMID[32031796]
NPO18703 Castela texana Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[8984156]
NPO18703 Castela texana Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17090 Epipedobates tricolor Species Dendrobatidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14446 Selaginella doederleinii Species Selaginellaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7731 Lactuca serriola Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5234 Myrica nagi Species Myricaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15373 Actaea dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14446 Selaginella doederleinii Species Selaginellaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7731 Lactuca serriola Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5234 Myrica nagi Species Myricaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7731 Lactuca serriola Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14446 Selaginella doederleinii Species Selaginellaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15373 Actaea dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5234 Myrica nagi Species Myricaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5234 Myrica nagi Species Myricaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15373 Actaea dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO17090 Epipedobates tricolor Species Dendrobatidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18703 Castela texana Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14446 Selaginella doederleinii Species Selaginellaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5234 Myrica nagi Species Myricaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15373 Actaea dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17020 Miscanthus floridulus Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19857 Schizothrix muelleri Species Schizotrichaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO7731 Lactuca serriola Species Asteraceae 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 NPC114268 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
1.0 High Similarity NPC484295

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC114268 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