Natural Product: NPC268668

Natural Product IDNPC268668
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 XCVOCJFOQNDTNC-ZNDRGHTASA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5488575
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:0002207] O-glycosyl compounds

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 XCVOCJFOQNDTNC-ZNDRGHTASA-N
Standard InCHI InChI=1S/C15H16O9/c1-5-11(18)13(20)14(21)15(23-5)24-9-4-22-8-3-6(16)2-7(17)10(8)12(9)19/h2-5,11,13-18,20-21H,1H3/t5-,11-,13+,14+,15-/m0/s1
SMILES C[C@H]1[C@@H]([C@H]([C@H]([C@@H](O1)Oc1coc2cc(cc(c2c1=O)O)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   340.08 Volume:   308.257
?
Van der Waals volume.
Dense:   1.103 LogP:   1.095
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.616
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.341
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   149.82
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   5.0 Rings:   3.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.483 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.993 Fsp3:   0.4
MCE-18:   69.524
?
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:   0.529 Fluc inhibitor:   0.047
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.586
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.507
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.211 Promiscuous compounds:   0.604

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.134 MDCK Permeability:   -5.218
Pgp-inhibitor:   0.0 Pgp-substrate:   0.622
PAMPA:   0.975
?
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):   0.353
20% Bioavailability (F20%):   0.334 30% Bioavailability (F30%):   0.975
50% Bioavailability (F50%):   0.987

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.031 MRP1:   0.152
Plasma Protein Binding (PPB):   82.605% Volume Distribution (VD):   -0.096
Fu: 18.263%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.951
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.754
BSEP inhibitor:   0.006

ADMET: Metabolism

CYP1A2-inhibitor:   0.231 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.079 CYP2C9-substrate:   0.029
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.525
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.069
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.94
HLM stability:   0.716
?
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):  2.72 Half-life (T1/2):  3.708

ADMET: Toxicity

hERG Blockers:  0.03 hERG Blockers (10um):  0.286
Human Hepatotoxicity (H-HT):  0.483 Drug-induced Liver Injury (DILI):  0.887
AMES Toxicity:  0.812 Rat Oral Acute Toxicity:  0.278
Maximum Recommended Daily Dose:  0.316 Skin Sensitization:  0.911
Carcinogencity:  0.256 Eye Corrosion:  0.004
Eye Irritation:  0.971 Respiratory Toxicity:  0.327
Drug-induced Neurotoxicity:  0.023 Ototoxicity:  0.53
Hematotoxicity:  0.149 Drug-induced Nephrotoxicity:  0.294
Genotoxicity:  0.911 RPMI-8226 Immunitoxicity:  0.166
A549 Cytotoxicity:  0.445 Hek293 Cytotoxicity:  0.449
BCF:   0.385
?
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:   3.051
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.377
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.57
?
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
NPO15116 Astilbe thunbergii Species Saxifragaceae Eukaryota Rhizomes n.a. n.a. PMID[9722485]
NPO15116 Astilbe thunbergii Species Saxifragaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15116 Astilbe thunbergii Species Saxifragaceae 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
NPT35 Others n.a. n.a. Activity = 98.5 % PMID[9722485]
NPT35 Others n.a. n.a. Activity = 100.0 % PMID[9722485]
NPT2 Others Unspecified n.a. Activity = 79.4 % PMID[9722485]
NPT2 Others Unspecified n.a. Activity = 332.8 % PMID[9722485]

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 NPC268668 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
0.8226 Intermediate Similarity NPC78697
0.7188 Intermediate Similarity NPC262699
0.7188 Intermediate Similarity NPC131217
0.6528 Remote Similarity NPC111929
0.6528 Remote Similarity NPC320283
0.6528 Remote Similarity NPC41121
0.6301 Remote Similarity NPC135599
0.6301 Remote Similarity NPC73855
0.6301 Remote Similarity NPC113968
0.6301 Remote Similarity NPC328940
0.6301 Remote Similarity NPC277174
0.6301 Remote Similarity NPC606877
0.6216 Remote Similarity NPC127546
0.6216 Remote Similarity NPC57625
0.6216 Remote Similarity NPC173637
0.6216 Remote Similarity NPC317489
0.6216 Remote Similarity NPC223424
0.6216 Remote Similarity NPC600591
0.6133 Remote Similarity NPC265530
0.5897 Remote Similarity NPC219904
0.575 Remote Similarity NPC223747
0.5412 Remote Similarity NPC173582
0.5412 Remote Similarity NPC265885
0.5412 Remote Similarity NPC181465
0.5412 Remote Similarity NPC215710
0.5412 Remote Similarity NPC473438
0.5412 Remote Similarity NPC253788
0.5385 Remote Similarity NPC77672
0.5385 Remote Similarity NPC133671
0.5385 Remote Similarity NPC135391
0.5385 Remote Similarity NPC78263
0.5385 Remote Similarity NPC250069
0.5375 Remote Similarity NPC138540
0.5316 Remote Similarity NPC156457
0.5233 Remote Similarity NPC39834
0.519 Remote Similarity NPC19388
0.519 Remote Similarity NPC240431
0.519 Remote Similarity NPC249281
0.519 Remote Similarity NPC55786
0.519 Remote Similarity NPC348541
0.5172 Remote Similarity NPC203259
0.5172 Remote Similarity NPC33054
0.5172 Remote Similarity NPC176740
0.5172 Remote Similarity NPC471725
0.5172 Remote Similarity NPC134532
0.5172 Remote Similarity NPC602582
0.5125 Remote Similarity NPC145038
0.5125 Remote Similarity NPC56077
0.5125 Remote Similarity NPC281131
0.5125 Remote Similarity NPC64305
0.5125 Remote Similarity NPC253662
0.5125 Remote Similarity NPC179950
0.5125 Remote Similarity NPC88789
0.5125 Remote Similarity NPC491374
0.5122 Remote Similarity NPC481043
0.5119 Remote Similarity NPC476215
0.5062 Remote Similarity NPC46420

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC268668 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
0.5172 Remote Similarity NPD6797 Phase 2

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