Natural Product: NPC219428

Natural Product IDNPC219428
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 GYFFKZTYYAFCTR-QHEBTOHLSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3092676
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000129] Alcohols and polyols
          • [CHEMONTID:0001292] Cyclic alcohols and derivatives
            • [CHEMONTID:0002509] Cyclitols and derivatives
              • [CHEMONTID:0002512] Quinic acids and derivatives

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 GYFFKZTYYAFCTR-QHEBTOHLSA-N
Standard InCHI InChI=1S/C16H18O9/c17-9-3-1-8(5-10(9)18)2-4-13(21)25-14-11(19)6-16(24,15(22)23)7-12(14)20/h1-5,11-12,14,17-20,24H,6-7H2,(H,22,23)/b4-2+/t11-,12-,14-,16-/m1/s1
SMILES c1cc(c(cc1/C=C/C(=O)O[C@@H]1[C@@H](C[C@@](C[C@H]1O)(C(=O)O)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   354.1 Volume:   331.473
?
Van der Waals volume.
Dense:   1.068 LogP:   0.651
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.185
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.505
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   15.0
TPSA:   164.75
?
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:   0.234 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.585 Fsp3:   0.375
MCE-18:   60.273
?
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:   1 PAINS Alert:   1
Colloidal aggregators:   0.536 Fluc inhibitor:   0.956
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.129
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.338
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.458 Promiscuous compounds:   0.438

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.374 MDCK Permeability:   -5.074
Pgp-inhibitor:   0.0 Pgp-substrate:   0.22
PAMPA:   1.0
?
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):   0.081
20% Bioavailability (F20%):   0.994 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.335
Plasma Protein Binding (PPB):   44.212% Volume Distribution (VD):   -0.244
Fu: 55.649%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.013
BSEP inhibitor:   0.002

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.117
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.128
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.007
HLM stability:   0.01
?
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):  2.96 Half-life (T1/2):  2.887

ADMET: Toxicity

hERG Blockers:  0.01 hERG Blockers (10um):  0.059
Human Hepatotoxicity (H-HT):  0.502 Drug-induced Liver Injury (DILI):  0.255
AMES Toxicity:  0.226 Rat Oral Acute Toxicity:  0.074
Maximum Recommended Daily Dose:  0.722 Skin Sensitization:  0.987
Carcinogencity:  0.215 Eye Corrosion:  0.113
Eye Irritation:  0.905 Respiratory Toxicity:  0.128
Drug-induced Neurotoxicity:  0.006 Ototoxicity:  0.862
Hematotoxicity:  0.062 Drug-induced Nephrotoxicity:  0.59
Genotoxicity:  0.751 RPMI-8226 Immunitoxicity:  0.02
A549 Cytotoxicity:  0.182 Hek293 Cytotoxicity:  0.047
BCF:   0.391
?
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:   2.958
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.474
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.859
?
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
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flowers n.a. n.a. DOI[10.1002/elan.200403102]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flowers n.a. n.a. DOI[10.1016/j.foodchem.2012.02.124]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flowers n.a. n.a. PMID[11077184]
NPO29221 Sarcandra glabra Species Chloranthaceae Eukaryota Whole plant n.a. n.a. PMID[16643038]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flowers n.a. n.a. PMID[17328234]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flower buds n.a. n.a. PMID[18321056]
NPO29221 Sarcandra glabra Species Chloranthaceae Eukaryota n.a. n.a. n.a. PMID[20038159]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. flower n.a. PMID[21804227]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. flower bud n.a. PMID[21942812]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota flower buds Henan province, China 2005-MAY PMID[21942812]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. leaf n.a. PMID[23265495]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flower buds n.a. n.a. PMID[24279769]
NPO29221 Sarcandra glabra Species Chloranthaceae Eukaryota aerial part n.a. n.a. PMID[25442304]
NPO29221 Sarcandra glabra Species Chloranthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29221 Sarcandra glabra Species Chloranthaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29221 Sarcandra glabra Species Chloranthaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29221 Sarcandra glabra Species Chloranthaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29221 Sarcandra glabra Species Chloranthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1515 Lonicera japonica Species Caprifoliaceae 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
NPT380 Cell line U-251 Homo sapiens Activity = 52.79 % PMID[25442304]
NPT76 Cell line C6 Rattus norvegicus Activity = 132.64 % PMID[18817444]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition < 30.0 % PMID[24279769]

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 NPC219428 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
0.7458 Intermediate Similarity NPC206095
0.7458 Intermediate Similarity NPC35702
0.7458 Intermediate Similarity NPC224389
0.7193 Intermediate Similarity NPC13818
0.7119 Intermediate Similarity NPC319628
0.7115 Intermediate Similarity NPC474275
0.7 Intermediate Similarity NPC37250
0.7 Intermediate Similarity NPC142703
0.7 Intermediate Similarity NPC152942
0.7 Intermediate Similarity NPC9991
0.7 Intermediate Similarity NPC302857
0.7 Intermediate Similarity NPC600892
0.6984 Remote Similarity NPC477335
0.6721 Remote Similarity NPC471027
0.6667 Remote Similarity NPC297517
0.6567 Remote Similarity NPC42464
0.6452 Remote Similarity NPC477333
0.6316 Remote Similarity NPC488563
0.6271 Remote Similarity NPC26241
0.6182 Remote Similarity NPC224208
0.6182 Remote Similarity NPC41661
0.6111 Remote Similarity NPC233669
0.6 Remote Similarity NPC281277
0.5968 Remote Similarity NPC474875
0.5946 Remote Similarity NPC145425
0.5893 Remote Similarity NPC309434
0.5818 Remote Similarity NPC217052
0.5818 Remote Similarity NPC329344
0.5818 Remote Similarity NPC237506
0.5818 Remote Similarity NPC32626
0.5763 Remote Similarity NPC251407
0.5763 Remote Similarity NPC168653
0.5672 Remote Similarity NPC284948
0.5672 Remote Similarity NPC303090
0.5672 Remote Similarity NPC301382
0.5672 Remote Similarity NPC37331
0.5614 Remote Similarity NPC147192
0.5522 Remote Similarity NPC278068
0.5397 Remote Similarity NPC475695
0.5385 Remote Similarity NPC179505
0.5357 Remote Similarity NPC488321
0.5357 Remote Similarity NPC488319
0.5357 Remote Similarity NPC488320
0.5352 Remote Similarity NPC220664
0.5333 Remote Similarity NPC132921
0.5323 Remote Similarity NPC258469
0.5323 Remote Similarity NPC43158
0.5323 Remote Similarity NPC610147
0.5294 Remote Similarity NPC477334
0.5278 Remote Similarity NPC156875
0.5246 Remote Similarity NPC470849
0.5246 Remote Similarity NPC474895
0.5224 Remote Similarity NPC67349
0.5224 Remote Similarity NPC279676
0.5192 Remote Similarity NPC226250
0.5167 Remote Similarity NPC114242
0.5139 Remote Similarity NPC322660
0.5079 Remote Similarity NPC18074
0.5079 Remote Similarity NPC470848
0.5079 Remote Similarity NPC182217
0.5079 Remote Similarity NPC5419
0.5079 Remote Similarity NPC25581
0.5079 Remote Similarity NPC61
0.5075 Remote Similarity NPC277315
0.5075 Remote Similarity NPC472016
0.5075 Remote Similarity NPC192831

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC219428 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
0.5672 Remote Similarity NPD6190 Approved

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