Natural Product: NPC68286

Natural Product IDNPC68286
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 WWEKCPWUOZWBRI-USXYKIIOSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5748571
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001111] Flavonoid glycosides
          • [CHEMONTID:0001583] Flavonoid O-glycosides
            • [CHEMONTID:0003540] Flavonoid-8-O-glycosides

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 WWEKCPWUOZWBRI-USXYKIIOSA-N
Standard InCHI InChI=1S/C21H20O12/c22-6-11-13(26)15(28)17(30)21(31-11)33-19-10(25)5-9(24)12-14(27)16(29)18(32-20(12)19)7-1-3-8(23)4-2-7/h1-5,11,13,15,17,21-26,28-30H,6H2/t11-,13-,15+,17-,21+/m0/s1
SMILES c1cc(ccc1c1c(c(=O)c2c(cc(c(c2o1)O[C@@H]1[C@H]([C@@H]([C@H]([C@H](CO)O1)O)O)O)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   464.1 Volume:   421.937
?
Van der Waals volume.
Dense:   1.1 LogP:   0.19
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.011
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.717
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   24.0
TPSA:   210.51
?
Topological Polar Surface Area.
 H-Bond Acceptor:   12.0
H-Bond Donor:   8.0 Rings:   4.0
Heavy Atoms:   12.0

MedChem Properties

QED Drug-Likeness Score:   0.245 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.051 Fsp3:   0.286
MCE-18:   91.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.66 Fluc inhibitor:   0.291
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.815
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.54
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.28 Promiscuous compounds:   0.905

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.478 MDCK Permeability:   -4.845
Pgp-inhibitor:   0.001 Pgp-substrate:   0.126
PAMPA:   0.996
?
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):   0.556
20% Bioavailability (F20%):   0.197 30% Bioavailability (F30%):   0.98
50% Bioavailability (F50%):   0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.272
Plasma Protein Binding (PPB):   87.173% Volume Distribution (VD):   -0.098
Fu: 11.368%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.991
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.857
BSEP inhibitor:   0.043

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.017
CYP2C9-inhibitor:   0.029 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.029
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.052
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.997
HLM stability:   0.841
?
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):  2.356 Half-life (T1/2):  3.322

ADMET: Toxicity

hERG Blockers:  0.006 hERG Blockers (10um):  0.151
Human Hepatotoxicity (H-HT):  0.507 Drug-induced Liver Injury (DILI):  0.818
AMES Toxicity:  0.679 Rat Oral Acute Toxicity:  0.109
Maximum Recommended Daily Dose:  0.075 Skin Sensitization:  0.982
Carcinogencity:  0.135 Eye Corrosion:  0.0
Eye Irritation:  0.87 Respiratory Toxicity:  0.111
Drug-induced Neurotoxicity:  0.006 Ototoxicity:  0.607
Hematotoxicity:  0.075 Drug-induced Nephrotoxicity:  0.331
Genotoxicity:  0.698 RPMI-8226 Immunitoxicity:  0.147
A549 Cytotoxicity:  0.604 Hek293 Cytotoxicity:  0.334
BCF:   0.728
?
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:   3.226
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.377
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.88
?
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
NPO21528 Equisetum arvense Species Equisetaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24089 Alcea rosea Species Malvaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10084 Equisetum hyemale Species Equisetaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21528 Equisetum arvense Species Equisetaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10084 Equisetum hyemale Species Equisetaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21528 Equisetum arvense Species Equisetaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24089 Alcea rosea Species Malvaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21528 Equisetum arvense Species Equisetaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24089 Alcea rosea Species Malvaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO10084 Equisetum hyemale Species Equisetaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO10084 Equisetum hyemale Species Equisetaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24089 Alcea rosea Species Malvaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21528 Equisetum arvense Species Equisetaceae 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 NPC68286 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
0.8841 High Similarity NPC282987
0.7568 Intermediate Similarity NPC8573
0.7105 Intermediate Similarity NPC323593
0.7105 Intermediate Similarity NPC203500
0.6795 Remote Similarity NPC84265
0.675 Remote Similarity NPC197285
0.65 Remote Similarity NPC21100
0.6329 Remote Similarity NPC77672
0.6329 Remote Similarity NPC133671
0.6329 Remote Similarity NPC135391
0.6329 Remote Similarity NPC78263
0.6329 Remote Similarity NPC250069
0.625 Remote Similarity NPC277205
0.625 Remote Similarity NPC37919
0.625 Remote Similarity NPC259152
0.6207 Remote Similarity NPC183672
0.6098 Remote Similarity NPC198324
0.6053 Remote Similarity NPC94777
0.6024 Remote Similarity NPC168584
0.6024 Remote Similarity NPC49344
0.6024 Remote Similarity NPC307938
0.6 Remote Similarity NPC471416
0.6 Remote Similarity NPC601586
0.5976 Remote Similarity NPC245014
0.5926 Remote Similarity NPC476405
0.5926 Remote Similarity NPC108831
0.5926 Remote Similarity NPC182634
0.5904 Remote Similarity NPC117260
0.5862 Remote Similarity NPC472607
0.5854 Remote Similarity NPC145038
0.5854 Remote Similarity NPC56077
0.5854 Remote Similarity NPC281131
0.5854 Remote Similarity NPC253662
0.5854 Remote Similarity NPC179950
0.5854 Remote Similarity NPC88789
0.5854 Remote Similarity NPC491374
0.5854 Remote Similarity NPC609879
0.5833 Remote Similarity NPC285197
0.5783 Remote Similarity NPC488080
0.5783 Remote Similarity NPC169977
0.5765 Remote Similarity NPC486578
0.5765 Remote Similarity NPC601710
0.5732 Remote Similarity NPC39360
0.5732 Remote Similarity NPC254306
0.5732 Remote Similarity NPC29763
0.5732 Remote Similarity NPC210003
0.5663 Remote Similarity NPC297987
0.5632 Remote Similarity NPC203050
0.5632 Remote Similarity NPC225434
0.5604 Remote Similarity NPC169733
0.5556 Remote Similarity NPC288084
0.5542 Remote Similarity NPC83283
0.5542 Remote Similarity NPC143851
0.5517 Remote Similarity NPC136761
0.5476 Remote Similarity NPC93337
0.5476 Remote Similarity NPC64305
0.5476 Remote Similarity NPC146792
0.5465 Remote Similarity NPC191306
0.5465 Remote Similarity NPC60735
0.5465 Remote Similarity NPC26230
0.5412 Remote Similarity NPC24043
0.5412 Remote Similarity NPC105025
0.5402 Remote Similarity NPC120099
0.5402 Remote Similarity NPC609478
0.5357 Remote Similarity NPC19388
0.5357 Remote Similarity NPC240431
0.5357 Remote Similarity NPC55786
0.5349 Remote Similarity NPC472459
0.5341 Remote Similarity NPC88023
0.5341 Remote Similarity NPC116458
0.5341 Remote Similarity NPC246943
0.5341 Remote Similarity NPC309025
0.5275 Remote Similarity NPC139320
0.5269 Remote Similarity NPC131745
0.5258 Remote Similarity NPC287889
0.525 Remote Similarity NPC78697
0.5238 Remote Similarity NPC111929
0.5238 Remote Similarity NPC320283
0.5238 Remote Similarity NPC41121
0.5233 Remote Similarity NPC472385
0.5233 Remote Similarity NPC610763
0.5227 Remote Similarity NPC148710
0.5222 Remote Similarity NPC477848
0.5205 Remote Similarity NPC201451
0.52 Remote Similarity NPC610401
0.5176 Remote Similarity NPC238376
0.5172 Remote Similarity NPC42773
0.5172 Remote Similarity NPC45522
0.5172 Remote Similarity NPC325555
0.5172 Remote Similarity NPC226304
0.5161 Remote Similarity NPC156869
0.5119 Remote Similarity NPC67037
0.5119 Remote Similarity NPC255615
0.5116 Remote Similarity NPC136042
0.5116 Remote Similarity NPC189142
0.5116 Remote Similarity NPC77660
0.5114 Remote Similarity NPC210094
0.5111 Remote Similarity NPC170052
0.5111 Remote Similarity NPC135846
0.5057 Remote Similarity NPC84362
0.5056 Remote Similarity NPC101026
0.5056 Remote Similarity NPC488077
0.5056 Remote Similarity NPC601144

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC68286 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