Natural Product: NPC472024

Natural Product IDNPC472024
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 LRRJMKSXWYAANN-YYMOATHLSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3326611
PubChem CID n.a.
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 LRRJMKSXWYAANN-YYMOATHLSA-N
Standard InCHI InChI=1S/C16H24O9/c1-23-11-5-8(4-9(19)6-17)2-3-10(11)24-16-15(22)14(21)13(20)12(7-18)25-16/h2-3,5,9,12-22H,4,6-7H2,1H3/t9-,12-,13-,14+,15-,16-/m1/s1
SMILES COC1=C(C=CC(=C1)CC(CO)O)OC2C(C(C(C(O2)CO)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   360.14 Volume:   339.382
?
Van der Waals volume.
Dense:   1.061 LogP:   -1.205
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.524
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.32
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   12.0
TPSA:   149.07
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   6.0 Rings:   2.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.318 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.674 Fsp3:   0.625
MCE-18:   50.769
?
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:   0.031 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.019
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.136
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.248 Promiscuous compounds:   0.092

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.829 MDCK Permeability:   -4.886
Pgp-inhibitor:   0.0 Pgp-substrate:   0.923
PAMPA:   0.997
?
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):   0.983
20% Bioavailability (F20%):   0.535 30% Bioavailability (F30%):   0.955
50% Bioavailability (F50%):   0.973

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.048 MRP1:   0.464
Plasma Protein Binding (PPB):   45.206% Volume Distribution (VD):   -0.468
Fu: 59.829%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.04
OATP1B3 inhibitor:   0.93 BCRP inhibitor:   0.072
BSEP inhibitor:   0.013

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.973 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.129 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.073 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.001
HLM stability:   0.003
?
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):  2.471 Half-life (T1/2):  2.304

ADMET: Toxicity

hERG Blockers:  0.076 hERG Blockers (10um):  0.304
Human Hepatotoxicity (H-HT):  0.505 Drug-induced Liver Injury (DILI):  0.097
AMES Toxicity:  0.459 Rat Oral Acute Toxicity:  0.03
Maximum Recommended Daily Dose:  0.025 Skin Sensitization:  0.21
Carcinogencity:  0.124 Eye Corrosion:  0.0
Eye Irritation:  0.063 Respiratory Toxicity:  0.007
Drug-induced Neurotoxicity:  0.098 Ototoxicity:  0.99
Hematotoxicity:  0.114 Drug-induced Nephrotoxicity:  0.163
Genotoxicity:  0.005 RPMI-8226 Immunitoxicity:  0.05
A549 Cytotoxicity:  0.046 Hek293 Cytotoxicity:  0.197
BCF:   0.147
?
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:   2.095
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.921
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.793
?
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
NPO6648 Piper retrofractum Species Piperaceae Eukaryota Fruits n.a. n.a. PMID[23506561]
NPO6648 Piper retrofractum Species Piperaceae Eukaryota leaves n.a. n.a. PMID[25127165]
NPO6648 Piper retrofractum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6648 Piper retrofractum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6648 Piper retrofractum Species Piperaceae 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
NPT60 Individual protein Lysosomal alpha-glucosidase Homo sapiens Inhibition = 11.74 % PMID[24697496]

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 = 0.55 uM PubChem BioAssay data set
NPT35 Others n.a. n.a. Activity = 2.88 uM PMID[16933872]

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 NPC472024 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
0.8431 Intermediate Similarity NPC270849
0.7925 Intermediate Similarity NPC26653
0.7925 Intermediate Similarity NPC80600
0.7692 Intermediate Similarity NPC9912
0.717 Intermediate Similarity NPC166040
0.6552 Remote Similarity NPC248355
0.6462 Remote Similarity NPC158635
0.6462 Remote Similarity NPC229882
0.6441 Remote Similarity NPC55040
0.6364 Remote Similarity NPC69513
0.6333 Remote Similarity NPC302378
0.6327 Remote Similarity NPC228907
0.6296 Remote Similarity NPC60589
0.6296 Remote Similarity NPC469708
0.629 Remote Similarity NPC604095
0.6269 Remote Similarity NPC227902
0.6176 Remote Similarity NPC471063
0.614 Remote Similarity NPC215833
0.6129 Remote Similarity NPC276753
0.6129 Remote Similarity NPC205796
0.6111 Remote Similarity NPC25817
0.6032 Remote Similarity NPC37468
0.6032 Remote Similarity NPC246947
0.6 Remote Similarity NPC479029
0.5972 Remote Similarity NPC245615
0.5882 Remote Similarity NPC61594
0.5846 Remote Similarity NPC210192
0.5797 Remote Similarity NPC56735
0.5753 Remote Similarity NPC299706
0.5753 Remote Similarity NPC115466
0.5753 Remote Similarity NPC39657
0.5753 Remote Similarity NPC61604
0.5714 Remote Similarity NPC299144
0.5694 Remote Similarity NPC217635
0.569 Remote Similarity NPC48863
0.569 Remote Similarity NPC251981
0.569 Remote Similarity NPC13745
0.5667 Remote Similarity NPC479028
0.5667 Remote Similarity NPC479031
0.5667 Remote Similarity NPC19470
0.5636 Remote Similarity NPC153149
0.5606 Remote Similarity NPC189115
0.5606 Remote Similarity NPC475096
0.56 Remote Similarity NPC46092
0.56 Remote Similarity NPC470950
0.56 Remote Similarity NPC163635
0.5571 Remote Similarity NPC18979
0.5571 Remote Similarity NPC279298
0.5556 Remote Similarity NPC276195
0.5556 Remote Similarity NPC212729
0.5556 Remote Similarity NPC604498
0.5526 Remote Similarity NPC486548
0.5526 Remote Similarity NPC129417
0.5526 Remote Similarity NPC283995
0.5455 Remote Similarity NPC217854
0.5455 Remote Similarity NPC269242
0.5441 Remote Similarity NPC148273
0.5439 Remote Similarity NPC609376
0.5429 Remote Similarity NPC286235
0.5424 Remote Similarity NPC610709
0.5397 Remote Similarity NPC104167
0.5385 Remote Similarity NPC294166
0.5385 Remote Similarity NPC115022
0.5357 Remote Similarity NPC294470
0.5352 Remote Similarity NPC79957
0.5352 Remote Similarity NPC38041
0.5352 Remote Similarity NPC22150
0.5345 Remote Similarity NPC226712
0.5345 Remote Similarity NPC608788
0.5323 Remote Similarity NPC210015
0.5323 Remote Similarity NPC210478
0.5303 Remote Similarity NPC479030
0.527 Remote Similarity NPC93924
0.5263 Remote Similarity NPC152722
0.5254 Remote Similarity NPC80098
0.5254 Remote Similarity NPC145900
0.5246 Remote Similarity NPC218685
0.5246 Remote Similarity NPC49074
0.5195 Remote Similarity NPC185307
0.5161 Remote Similarity NPC162093
0.5147 Remote Similarity NPC475084
0.5139 Remote Similarity NPC476411
0.5128 Remote Similarity NPC486549
0.5128 Remote Similarity NPC470235
0.5088 Remote Similarity NPC192810
0.5085 Remote Similarity NPC200092
0.5085 Remote Similarity NPC12308
0.5082 Remote Similarity NPC310661
0.5077 Remote Similarity NPC247146
0.5063 Remote Similarity NPC486546

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC472024 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
0.5345 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