Natural Product: NPC132304

Natural Product IDNPC132304
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Ginkolide B
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL514432
PubChem CID 6324617
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones
          • [CHEMONTID:0001538] Diterpene lactones
            • [CHEMONTID:0001768] Ginkgolides and bilobalides

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 SQOJOAFXDQDRGF-MMQTXUMRSA-N
Standard InCHI InChI=1S/C20H24O10/c1-6-12(23)28-11-9(21)18-8-5-7(16(2,3)4)17(18)10(22)13(24)29-15(17)30-20(18,14(25)27-8)19(6,11)26/h6-11,15,21-22,26H,5H2,1-4H3/t6-,7+,8-,9+,10+,11+,15+,17+,18+,19-,20-/m1/s1
SMILES O=C1O[C@@H]2[C@@]([C@@H]1C)(O)[C@@]13[C@]4([C@H]2O)[C@H](OC3=O)C[C@H]([C@@]24[C@H](O1)OC(=O)[C@@H]2O)C(C)(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   424.14 Volume:   383.13
?
Van der Waals volume.
Dense:   1.107 LogP:   1.157
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.604
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.195
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   27.0
TPSA:   148.82
?
Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   3.0 Rings:   6.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.314 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.186 Fsp3:   0.85
MCE-18:   156.892
?
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:   0.386 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.006
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.262 Promiscuous compounds:   0.388

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.441 MDCK Permeability:   -4.962
Pgp-inhibitor:   0.007 Pgp-substrate:   0.553
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):   0.056
20% Bioavailability (F20%):   0.006 30% Bioavailability (F30%):   0.14
50% Bioavailability (F50%):   0.853

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.331
Plasma Protein Binding (PPB):   29.021% Volume Distribution (VD):   -0.15
Fu: 66.21%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.009
BSEP inhibitor:   0.061

ADMET: Metabolism

CYP1A2-inhibitor:   0.021 CYP1A2-substrate:   0.102
CYP2C19-inhibitor:   0.9 CYP2C19-substrate:   0.231
CYP2C9-inhibitor:   0.005 CYP2C9-substrate:   0.147
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.825
CYP3A4-inhibitor:   0.992 CYP3A4-substrate:   0.99
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.861
HLM stability:   0.796
?
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):  1.707 Half-life (T1/2):  4.399

ADMET: Toxicity

hERG Blockers:  0.012 hERG Blockers (10um):  0.249
Human Hepatotoxicity (H-HT):  0.451 Drug-induced Liver Injury (DILI):  0.248
AMES Toxicity:  0.759 Rat Oral Acute Toxicity:  0.814
Maximum Recommended Daily Dose:  0.882 Skin Sensitization:  0.996
Carcinogencity:  0.421 Eye Corrosion:  0.057
Eye Irritation:  0.74 Respiratory Toxicity:  0.885
Drug-induced Neurotoxicity:  0.2 Ototoxicity:  0.549
Hematotoxicity:  0.681 Drug-induced Nephrotoxicity:  0.898
Genotoxicity:  0.98 RPMI-8226 Immunitoxicity:  0.344
A549 Cytotoxicity:  0.024 Hek293 Cytotoxicity:  0.092
BCF:   1.368
?
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:   4.064
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.925
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.283
?
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]
NPO26293 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. leaf n.a. DOI[10.1016/S0031-9422(01)00320-X]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flowers n.a. n.a. PMID[11077184]
NPO26293 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. leaf n.a. PMID[11738417]
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]
NPO26293 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. fruit n.a. PMID[21462031]
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]
NPO15473 Ocotea heterochroma Species Lauraceae Eukaryota leaves n.a. n.a. PMID[30188730]
NPO26293 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15473 Ocotea heterochroma Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26293 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26293 Ginkgo biloba Species Ginkgoaceae 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]
NPO26293 Ginkgo biloba Species Ginkgoaceae 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]
NPO26293 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO26293 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15473 Ocotea heterochroma Species Lauraceae 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
NPT1372 Individual protein Platelet activating factor receptor Cavia porcellus IC50 = 740.0 nM PMID[8478911]
NPT1372 Individual protein Platelet activating factor receptor Cavia porcellus EC50 = 180.0 nM PMID[8478911]
NPT1372 Individual protein Platelet activating factor receptor Cavia porcellus Ki = 880.0 nM PMID[12570381]
NPT1372 Individual protein Platelet activating factor receptor Cavia porcellus IC50 = 418.0 nM DOI[10.1016/0960-894X(95)00173-Q]
NPT274 Individual protein Platelet activating factor receptor Homo sapiens IC50 = 128.0 nM PMID[9871752]
NPT274 Individual protein Platelet activating factor receptor Homo sapiens Binding affinity = 0.6 uM PMID[9871752]
NPT274 Individual protein Platelet activating factor receptor Homo sapiens Binding affinity = 6.22 uM PMID[9871752]
NPT198 Individual protein Vitamin D receptor Homo sapiens Potency n.a. 89125.1 nM PubChem BioAssay data set
NPT11 Individual protein Guanine nucleotide-binding protein G(s), subunit alpha Homo sapiens Potency n.a. 11220.2 nM PubChem BioAssay data set
NPT1600 Individual protein Beta-glucuronidase Homo sapiens IC50 = 6630.0 nM PMID[31835168]
NPT426 Individual protein Glycine receptor subunit alpha-1 Homo sapiens IC50 = 2900.0 nM PMID[17352465]
NPT426 Individual protein Glycine receptor subunit alpha-1 Homo sapiens IC50 = 3162.28 nM PMID[17352465]
NPT426 Individual protein Glycine receptor subunit alpha-1 Homo sapiens IC50 = 2100.0 nM PMID[17352465]
NPT426 Individual protein Glycine receptor subunit alpha-1 Homo sapiens IC50 = 1995.26 nM PMID[17352465]
NPT426 Individual protein Glycine receptor subunit alpha-1 Homo sapiens IC50 = 1700.0 nM PMID[17352465]
NPT67 Individual protein Cholinesterase Equus caballus Inhibition = 9.99 % PMID[23062825]
NPT4324 Individual protein Glycine receptor subunit alpha-2 Homo sapiens IC50 = 3981.07 nM PMID[17352465]
NPT4324 Individual protein Glycine receptor subunit alpha-2 Homo sapiens IC50 = 3700.0 nM PMID[17352465]
NPT66 Individual protein Acetylcholinesterase Electrophorus electricus Inhibition = -7.35 % PMID[23062825]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1637 Organism Cydia pomonella Cydia pomonella FDI = 12.5 % PMID[21905729]
NPT1637 Organism Cydia pomonella Cydia pomonella FDI = 26.1 % PMID[21905729]
NPT1637 Organism Cydia pomonella Cydia pomonella FDI = 76.0 % PMID[21905729]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 72.0 ug.mL-1 PMID[11809061]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 78.4 % PMID[18396904]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 78.8 % PMID[18303851]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 930.0 nM PMID[19548690]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 118.0 % PMID[19548690]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 925.0 nM PMID[19880317]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 75600.0 nM PMID[19880317]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 999000.0 nM PMID[19880317]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 2350.0 nM PMID[20411974]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 83.5 % PMID[21524101]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 84.3 % PMID[21942812]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 78.0 % PMID[24279769]
NPT2 Others Unspecified n.a. IC50 = 19000.0 nM PMID[9644071]
NPT2 Others Unspecified n.a. IC50 = 80000.0 nM PMID[8786365]
NPT2 Others Unspecified n.a. Potency = 410.9 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 2238.7 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. IC50 = 930.0 nM PMID[19548690]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT605 Organism Homo sapiens Homo sapiens Fg = 1.03 n.a. PMID[20070106]
NPT605 Organism Homo sapiens Homo sapiens F_fraction = 0.88 n.a. PMID[20070106]
NPT605 Organism Homo sapiens Homo sapiens Fa = 0.9 n.a. PMID[20070106]





 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 NPC132304 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
1.0 High Similarity NPC123070
1.0 High Similarity NPC169089
0.7377 Intermediate Similarity NPC114365
0.7377 Intermediate Similarity NPC154962
0.7377 Intermediate Similarity NPC18044
0.7377 Intermediate Similarity NPC177518
0.6935 Remote Similarity NPC88890
0.6935 Remote Similarity NPC18433

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC132304 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
1.0 High Similarity NPD4056 Clinical (unspecified phase)
1.0 High Similarity NPD4057 Clinical (unspecified phase)

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