Natural Product: NPC280423

Natural Product IDNPC280423
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 XTIIKSGREOOAOR-XIKSMUEASA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11327449
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 XTIIKSGREOOAOR-XIKSMUEASA-N
Standard InCHI InChI=1S/C20H30O9/c1-3-4-9-27-16(22)8-6-12-5-7-13(14(10-12)26-2)28-20-19(25)18(24)17(23)15(11-21)29-20/h5,7,10,15,17-21,23-25H,3-4,6,8-9,11H2,1-2H3/t15-,17-,18+,19-,20-/m1/s1
SMILES CCCCOC(=O)CCc1ccc(c(c1)OC)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   414.19 Volume:   405.929
?
Van der Waals volume.
Dense:   1.02 LogP:   1.163
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.38
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.951
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   11.0 Rigid Bonds:   13.0
TPSA:   134.91
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.312 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.501 Fsp3:   0.65
MCE-18:   49.545
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.657 Fluc inhibitor:   0.01
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.029
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.085
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.11 Promiscuous compounds:   0.026

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.528 MDCK Permeability:   -4.9
Pgp-inhibitor:   0.018 Pgp-substrate:   0.223
PAMPA:   0.4
?
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):   0.555
20% Bioavailability (F20%):   0.282 30% Bioavailability (F30%):   0.957
50% Bioavailability (F50%):   0.962

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.018 MRP1:   0.128
Plasma Protein Binding (PPB):   84.239% Volume Distribution (VD):   -0.327
Fu: 14.444%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.072
BSEP inhibitor:   0.774

ADMET: Metabolism

CYP1A2-inhibitor:   0.005 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.005 CYP2C19-substrate:   0.039
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.009
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   0.025
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.04
?
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):  3.25 Half-life (T1/2):  1.947

ADMET: Toxicity

hERG Blockers:  0.058 hERG Blockers (10um):  0.175
Human Hepatotoxicity (H-HT):  0.403 Drug-induced Liver Injury (DILI):  0.698
AMES Toxicity:  0.621 Rat Oral Acute Toxicity:  0.012
Maximum Recommended Daily Dose:  0.015 Skin Sensitization:  0.982
Carcinogencity:  0.324 Eye Corrosion:  0.0
Eye Irritation:  0.271 Respiratory Toxicity:  0.008
Drug-induced Neurotoxicity:  0.008 Ototoxicity:  0.906
Hematotoxicity:  0.233 Drug-induced Nephrotoxicity:  0.841
Genotoxicity:  0.019 RPMI-8226 Immunitoxicity:  0.079
A549 Cytotoxicity:  0.013 Hek293 Cytotoxicity:  0.036
BCF:   0.606
?
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:   3.303
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.686
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.091
?
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
NPO11597 Stellaria dichotoma Species Caryophyllaceae Eukaryota n.a. n.a. n.a. PMID[15387643]
NPO11597.1 Stellaria dichotoma var. lanceolata Under-species Caryophyllaceae Eukaryota n.a. root n.a. PMID[15467234]
NPO11597 Stellaria dichotoma Species Caryophyllaceae Eukaryota n.a. n.a. n.a. PMID[16309326]
NPO11597.1 Stellaria dichotoma var. lanceolata Under-species Caryophyllaceae Eukaryota n.a. root n.a. PMID[21090796]
NPO11597.1 Stellaria dichotoma var. lanceolata Under-species Caryophyllaceae Eukaryota roots n.a. n.a. PMID[21090796]
NPO11597 Stellaria dichotoma Species Caryophyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11597.1 Stellaria dichotoma var. lanceolata Under-species Caryophyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11597.1 Stellaria dichotoma var. lanceolata Under-species Caryophyllaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11597.1 Stellaria dichotoma var. lanceolata Under-species Caryophyllaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11597 Stellaria dichotoma Species Caryophyllaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11597 Stellaria dichotoma Species Caryophyllaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11597 Stellaria dichotoma Species Caryophyllaceae 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 NPC280423 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
0.7419 Intermediate Similarity NPC26653
0.7143 Intermediate Similarity NPC80600
0.6462 Remote Similarity NPC472024
0.6462 Remote Similarity NPC270849
0.6 Remote Similarity NPC158635
0.6 Remote Similarity NPC229882
0.5909 Remote Similarity NPC9912
0.5844 Remote Similarity NPC227902
0.5758 Remote Similarity NPC166040
0.5634 Remote Similarity NPC302378
0.557 Remote Similarity NPC471063
0.5479 Remote Similarity NPC276753
0.5479 Remote Similarity NPC205796
0.5441 Remote Similarity NPC215833
0.5422 Remote Similarity NPC299706
0.5422 Remote Similarity NPC245615
0.5422 Remote Similarity NPC115466
0.5422 Remote Similarity NPC61604
0.5405 Remote Similarity NPC246947
0.5366 Remote Similarity NPC217635
0.5352 Remote Similarity NPC248355
0.5294 Remote Similarity NPC163635
0.5278 Remote Similarity NPC55040
0.5238 Remote Similarity NPC39657
0.5233 Remote Similarity NPC486548
0.5205 Remote Similarity NPC34456
0.52 Remote Similarity NPC37468
0.5147 Remote Similarity NPC69513
0.5125 Remote Similarity NPC61594
0.5116 Remote Similarity NPC46092
0.5116 Remote Similarity NPC470950
0.5109 Remote Similarity NPC485746
0.5065 Remote Similarity NPC187194
0.5062 Remote Similarity NPC56735
0.5057 Remote Similarity NPC129417
0.5057 Remote Similarity NPC283995

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC280423 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