Natural Product: NPC211084

Natural Product IDNPC211084
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 QLJIAZMTIULFGW-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 19744872
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003467] Linear 1,3-diarylpropanoids
        • [CHEMONTID:0001630] Chalcones and dihydrochalcones
          • [CHEMONTID:0003473] 2'-Hydroxy-dihydrochalcones

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 QLJIAZMTIULFGW-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H22O5/c1-12(2)3-9-15-17(23)11-18(24)19(20(15)25)16(22)10-6-13-4-7-14(21)8-5-13/h3-5,7-8,11,21,23-25H,6,9-10H2,1-2H3
SMILES CC(=CCc1c(cc(c(C(=O)CCc2ccc(cc2)O)c1O)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   342.15 Volume:   360.223
?
Van der Waals volume.
Dense:   0.95 LogP:   3.708
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.324
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.767
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   14.0
TPSA:   97.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.472 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.572 Fsp3:   0.25
MCE-18:   15.0
?
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:   0.772 Fluc inhibitor:   0.64
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.67
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.242
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.631 Promiscuous compounds:   0.073

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.922 MDCK Permeability:   -4.824
Pgp-inhibitor:   0.915 Pgp-substrate:   0.01
PAMPA:   0.253
?
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%):   0.114 30% Bioavailability (F30%):   0.9
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.832
Plasma Protein Binding (PPB):   92.974% Volume Distribution (VD):   0.484
Fu: 7.054%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.558
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.035 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.905 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.928 CYP2C9-substrate:   0.916
CYP2D6-inhibitor:   0.998 CYP2D6-substrate:   0.912
CYP3A4-inhibitor:   0.253 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):  7.055 Half-life (T1/2):  1.023

ADMET: Toxicity

hERG Blockers:  0.06 hERG Blockers (10um):  0.638
Human Hepatotoxicity (H-HT):  0.486 Drug-induced Liver Injury (DILI):  0.036
AMES Toxicity:  0.408 Rat Oral Acute Toxicity:  0.571
Maximum Recommended Daily Dose:  0.5 Skin Sensitization:  0.918
Carcinogencity:  0.208 Eye Corrosion:  0.004
Eye Irritation:  0.931 Respiratory Toxicity:  0.968
Drug-induced Neurotoxicity:  0.426 Ototoxicity:  0.28
Hematotoxicity:  0.121 Drug-induced Nephrotoxicity:  0.404
Genotoxicity:  0.917 RPMI-8226 Immunitoxicity:  0.046
A549 Cytotoxicity:  0.509 Hek293 Cytotoxicity:  0.733
BCF:   1.844
?
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:   4.574
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.899
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.292
?
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
NPO29535 Samadera indica Species Simaroubaceae Eukaryota n.a. n.a. n.a. DOI[10.1039/C39770000295]
NPO29535 Samadera indica Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[11429258]
NPO29535 Samadera indica Species Simaroubaceae Eukaryota n.a. stem n.a. PMID[8945767]
NPO6134 Vitis betulifolia Species Vitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2570 Cirsium wallichii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29535 Samadera indica Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4295 Agarum cribrosum Species n.a. Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO292 Aglaia elliptica Species Meliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1906 Catananche caerulea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO718 Corydalis calliantha Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2426 Corynascus setosus Species Chaetomiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4819 Dryocosmus kuriphilus Species Cynipidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1279 Fritillaria cirrhosa Species Liliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5424 Phebalium whitei Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5984 Rosa agrestis Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO574 Rumex nepalensis Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7912 Salvia urolepis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4566 Solanderia secunda Species Hydractiniidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3758 Stiretrus anchorago Species Pentatomidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5266 Strychnos ligustrina Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17074 Trichosurus vulpecula Species Phalangeridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7469 Veronica kellereri Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1279 Fritillaria cirrhosa Species Liliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO574 Rumex nepalensis Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO292 Aglaia elliptica Species Meliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1279 Fritillaria cirrhosa Species Liliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO574 Rumex nepalensis Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO574 Rumex nepalensis Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1279 Fritillaria cirrhosa Species Liliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO5424 Phebalium whitei Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5984 Rosa agrestis Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4295 Agarum cribrosum Species n.a. Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2426 Corynascus setosus Species Chaetomiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7469 Veronica kellereri Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO292 Aglaia elliptica Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29535 Samadera indica Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17074 Trichosurus vulpecula Species Phalangeridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6134 Vitis betulifolia Species Vitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1906 Catananche caerulea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1279 Fritillaria cirrhosa Species Liliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3758 Stiretrus anchorago Species Pentatomidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5266 Strychnos ligustrina Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7912 Salvia urolepis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO718 Corydalis calliantha Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4566 Solanderia secunda Species Hydractiniidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2570 Cirsium wallichii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4819 Dryocosmus kuriphilus Species Cynipidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO574 Rumex nepalensis Species Polygonaceae 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 NPC211084 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
0.8077 Intermediate Similarity NPC483966
0.6909 Remote Similarity NPC13575
0.6591 Remote Similarity NPC215392
0.6522 Remote Similarity NPC242895
0.6415 Remote Similarity NPC98254
0.566 Remote Similarity NPC63698
0.56 Remote Similarity NPC233056
0.5574 Remote Similarity NPC23126
0.551 Remote Similarity NPC133909
0.5472 Remote Similarity NPC91105
0.541 Remote Similarity NPC267846
0.5385 Remote Similarity NPC82225
0.5294 Remote Similarity NPC179494
0.5263 Remote Similarity NPC601405
0.5238 Remote Similarity NPC116513
0.52 Remote Similarity NPC607946
0.5156 Remote Similarity NPC483963
0.5088 Remote Similarity NPC282957
0.5088 Remote Similarity NPC65761

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC211084 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