Natural Product: NPC289204

Natural Product IDNPC289204
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 NEZJDVYDSZTRFS-RMPHRYRLSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 65080
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates
          • [CHEMONTID:0002105] Glycosyl compounds
            • [CHEMONTID:0004165] Phenolic 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 NEZJDVYDSZTRFS-RMPHRYRLSA-N
Standard InCHI InChI=1S/C12H16O6/c13-6-8-9(14)10(15)11(16)12(18-8)17-7-4-2-1-3-5-7/h1-5,8-16H,6H2/t8-,9-,10+,11-,12-/m1/s1
SMILES c1ccc(cc1)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   256.09 Volume:   243.827
?
Van der Waals volume.
Dense:   1.05 LogP:   -0.26
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.031
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.157
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   12.0
TPSA:   99.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.546 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.183 Fsp3:   0.5
MCE-18:   42.667
?
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:   0.394 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.082
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.007
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.401 Promiscuous compounds:   0.016

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.066 MDCK Permeability:   -4.912
Pgp-inhibitor:   0.003 Pgp-substrate:   0.326
PAMPA:   0.945
?
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):   0.91
20% Bioavailability (F20%):   0.353 30% Bioavailability (F30%):   0.965
50% Bioavailability (F50%):   0.817

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.853 MRP1:   0.088
Plasma Protein Binding (PPB):   60.117% Volume Distribution (VD):   -0.408
Fu: 44.198%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.97
OATP1B3 inhibitor:   0.98 BCRP inhibitor:   0.117
BSEP inhibitor:   0.016

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.002 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.172 CYP3A4-substrate:   0.53
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.426
HLM stability:   0.158
?
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):  2.116 Half-life (T1/2):  2.238

ADMET: Toxicity

hERG Blockers:  0.031 hERG Blockers (10um):  0.293
Human Hepatotoxicity (H-HT):  0.477 Drug-induced Liver Injury (DILI):  0.555
AMES Toxicity:  0.74 Rat Oral Acute Toxicity:  0.053
Maximum Recommended Daily Dose:  0.016 Skin Sensitization:  0.961
Carcinogencity:  0.139 Eye Corrosion:  0.004
Eye Irritation:  0.793 Respiratory Toxicity:  0.027
Drug-induced Neurotoxicity:  0.065 Ototoxicity:  0.698
Hematotoxicity:  0.172 Drug-induced Nephrotoxicity:  0.763
Genotoxicity:  0.032 RPMI-8226 Immunitoxicity:  0.095
A549 Cytotoxicity:  0.13 Hek293 Cytotoxicity:  0.065
BCF:   0.405
?
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:   2.579
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.955
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.034
?
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
NPO25825 Saussurea lappa Species Asteraceae Eukaryota Roots n.a. n.a. PMID[14510592]
NPO25825 Saussurea lappa Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[3572418]
NPO25825 Saussurea lappa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25825 Saussurea lappa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO25825 Saussurea lappa 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 NPC289204 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
0.8108 Intermediate Similarity NPC228907
0.7317 Intermediate Similarity NPC212729
0.7317 Intermediate Similarity NPC142319
0.7317 Intermediate Similarity NPC604498
0.7143 Intermediate Similarity NPC269242
0.6977 Remote Similarity NPC294470
0.6818 Remote Similarity NPC9248
0.6667 Remote Similarity NPC60589
0.6667 Remote Similarity NPC469708
0.6667 Remote Similarity NPC604439
0.6667 Remote Similarity NPC609376
0.6591 Remote Similarity NPC153149
0.6522 Remote Similarity NPC200092
0.6522 Remote Similarity NPC226712
0.6522 Remote Similarity NPC608788
0.6512 Remote Similarity NPC276195
0.6444 Remote Similarity NPC25817
0.6383 Remote Similarity NPC80098
0.6364 Remote Similarity NPC217854
0.6222 Remote Similarity NPC192810
0.6087 Remote Similarity NPC152722
0.6042 Remote Similarity NPC221090
0.6 Remote Similarity NPC484157
0.5918 Remote Similarity NPC214454
0.5882 Remote Similarity NPC251102
0.5882 Remote Similarity NPC210298
0.5882 Remote Similarity NPC604356
0.5882 Remote Similarity NPC606892
0.5833 Remote Similarity NPC12308
0.5769 Remote Similarity NPC26080
0.5769 Remote Similarity NPC165686
0.5769 Remote Similarity NPC164599
0.5714 Remote Similarity NPC145900
0.5686 Remote Similarity NPC218685
0.5636 Remote Similarity NPC146540
0.5625 Remote Similarity NPC299144
0.56 Remote Similarity NPC166168
0.56 Remote Similarity NPC166040
0.5577 Remote Similarity NPC479028
0.5577 Remote Similarity NPC83975
0.5577 Remote Similarity NPC23084
0.5577 Remote Similarity NPC479031
0.5556 Remote Similarity NPC222455
0.549 Remote Similarity NPC40377
0.549 Remote Similarity NPC310661
0.549 Remote Similarity NPC9912
0.5455 Remote Similarity NPC218003
0.5455 Remote Similarity NPC34456
0.5439 Remote Similarity NPC479374
0.54 Remote Similarity NPC69513
0.537 Remote Similarity NPC57751
0.5357 Remote Similarity NPC99515
0.5357 Remote Similarity NPC269421
0.5357 Remote Similarity NPC605646
0.5294 Remote Similarity NPC48863
0.5294 Remote Similarity NPC95292
0.5294 Remote Similarity NPC251981
0.5294 Remote Similarity NPC13745
0.5294 Remote Similarity NPC604209
0.5283 Remote Similarity NPC472024
0.5283 Remote Similarity NPC485268
0.5283 Remote Similarity NPC270849
0.5283 Remote Similarity NPC205054
0.5283 Remote Similarity NPC19470
0.5273 Remote Similarity NPC599943
0.5192 Remote Similarity NPC215833
0.5185 Remote Similarity NPC26653
0.5185 Remote Similarity NPC214910
0.5185 Remote Similarity NPC80600
0.5185 Remote Similarity NPC481303
0.5185 Remote Similarity NPC210478
0.5179 Remote Similarity NPC103409
0.5179 Remote Similarity NPC247146
0.5094 Remote Similarity NPC49074
0.5094 Remote Similarity NPC265442
0.5091 Remote Similarity NPC248355
0.5091 Remote Similarity NPC105827
0.5091 Remote Similarity NPC473044
0.5091 Remote Similarity NPC479029
0.5091 Remote Similarity NPC288349
0.5088 Remote Similarity NPC190714
0.5088 Remote Similarity NPC600105
0.5085 Remote Similarity NPC175976
0.5085 Remote Similarity NPC600107

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC289204 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
0.6522 Remote Similarity NPD1091 Pre-clinical

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