Natural Product: NPC279971

Natural Product IDNPC279971
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 FSVHIIPNYZDPPR-HWTDXWPBSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 86294835
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones
          • [CHEMONTID:0001543] Sesquiterpene lactones

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 FSVHIIPNYZDPPR-HWTDXWPBSA-N
Standard InCHI InChI=1S/C15H18O4/c1-6-4-11-13(8(3)15(18)19-11)14(17)12-7(2)10(16)5-9(6)12/h6,9,11,13-14,17H,3-5H2,1-2H3/t6-,9-,11+,13+,14-/m0/s1
SMILES C[C@H]1C[C@@H]2[C@@H](C(=C)C(=O)O2)[C@H](C2=C(C)C(=O)C[C@@H]12)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   262.12 Volume:   266.942
?
Van der Waals volume.
Dense:   0.982 LogP:   1.479
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.51
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.067
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   18.0
TPSA:   63.6
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.529 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.633 Fsp3:   0.6
MCE-18:   49.083
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.644 Fluc inhibitor:   0.002
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.266
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.001
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.541 Promiscuous compounds:   0.259

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.35 MDCK Permeability:   -4.976
Pgp-inhibitor:   0.11 Pgp-substrate:   0.014
PAMPA:   0.599
?
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):   0.045
20% Bioavailability (F20%):   0.702 30% Bioavailability (F30%):   0.311
50% Bioavailability (F50%):   0.579

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.031 MRP1:   0.856
Plasma Protein Binding (PPB):   63.888% Volume Distribution (VD):   0.131
Fu: 35.313%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.76
OATP1B3 inhibitor:   0.919 BCRP inhibitor:   0.002
BSEP inhibitor:   0.651

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.587
CYP2C19-inhibitor:   0.009 CYP2C19-substrate:   0.135
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.113
CYP3A4-inhibitor:   0.286 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.988
HLM stability:   0.708
?
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):  6.381 Half-life (T1/2):  2.078

ADMET: Toxicity

hERG Blockers:  0.018 hERG Blockers (10um):  0.204
Human Hepatotoxicity (H-HT):  0.756 Drug-induced Liver Injury (DILI):  0.963
AMES Toxicity:  0.95 Rat Oral Acute Toxicity:  0.673
Maximum Recommended Daily Dose:  0.45 Skin Sensitization:  0.999
Carcinogencity:  0.927 Eye Corrosion:  0.071
Eye Irritation:  0.846 Respiratory Toxicity:  0.478
Drug-induced Neurotoxicity:  0.835 Ototoxicity:  0.476
Hematotoxicity:  0.972 Drug-induced Nephrotoxicity:  0.965
Genotoxicity:  0.998 RPMI-8226 Immunitoxicity:  0.288
A549 Cytotoxicity:  0.777 Hek293 Cytotoxicity:  0.706
BCF:   0.56
?
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:   3.156
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.541
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.065
?
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
NPO25515 Garcinia speciosa Species Clusiaceae Eukaryota barks n.a. n.a. PMID[15620248]
NPO24708 Mikania micrantha Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[19267453]
NPO23707 Sinularia gyrosa Species Alcyoniidae Eukaryota n.a. n.a. n.a. PMID[20430633]
NPO23707 Sinularia gyrosa Species Alcyoniidae Eukaryota n.a. n.a. n.a. PMID[20499851]
NPO23998 Auxarthron reticulatum Species Onygenaceae Eukaryota n.a. n.a. n.a. PMID[24900275]
NPO6403 Phlegmariurus squarrosus Species Lycopodiaceae Eukaryota n.a. n.a. n.a. PMID[32941036]
NPO24708 Mikania micrantha Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[37635675]
NPO24662 Ulmus laevis Species Ulmaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22408 Aconitum polyschistum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20331 Aerva tomentosa Species Amaranthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23866 Anisocycla cymosa Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23134 Artemisia kaschgarica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23998 Auxarthron reticulatum Species Onygenaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24854 Beltrania rhombica Species Beltraniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24142 Cereus ocamponis Species Sagartiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25683 Columba livia Species Columbidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25241 Cordyla africana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23707 Sinularia gyrosa Species Alcyoniidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25313 Satureja douglasii Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25341 Sanango racemosum Species Gesneriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25115 Psychotria calocarpa Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6403 Phlegmariurus squarrosus Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25399 Patrinia intermedia Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24895 Parmelia springtonensis Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1827 Morinda elliptica Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24708 Mikania micrantha Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24242 Haminoea cymbalum Species Haminoeidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25515 Garcinia speciosa Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24950 Eupatorium aschenbornianum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25602 Crotalaria barbata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28627 Coptis trifolia Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28627 Coptis trifolia Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO25515 Garcinia speciosa Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22408 Aconitum polyschistum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22408 Aconitum polyschistum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25515 Garcinia speciosa Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24950 Eupatorium aschenbornianum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28627 Coptis trifolia Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24142 Cereus ocamponis Species Sagartiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23134 Artemisia kaschgarica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23707 Sinularia gyrosa Species Alcyoniidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1827 Morinda elliptica Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25341 Sanango racemosum Species Gesneriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25515 Garcinia speciosa Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24950 Eupatorium aschenbornianum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25241 Cordyla africana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23866 Anisocycla cymosa Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24242 Haminoea cymbalum Species Haminoeidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25683 Columba livia Species Columbidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6403 Phlegmariurus squarrosus Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25115 Psychotria calocarpa Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22408 Aconitum polyschistum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24662 Ulmus laevis Species Ulmaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20331 Aerva tomentosa Species Amaranthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23998 Auxarthron reticulatum Species Onygenaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24708 Mikania micrantha Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24854 Beltrania rhombica Species Beltraniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25602 Crotalaria barbata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25399 Patrinia intermedia Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28627 Coptis trifolia Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25313 Satureja douglasii Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24895 Parmelia springtonensis Species Parmeliaceae 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 NPC279971 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
0.549 Remote Similarity NPC69271
0.549 Remote Similarity NPC74673

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC279971 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