Natural Product: NPC18433

Natural Product IDNPC18433
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 AMOGMTLMADGEOQ-UDHFVGDGSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1299408
PubChem CID 15944764
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 AMOGMTLMADGEOQ-UDHFVGDGSA-N
Standard InCHI InChI=1S/C20H24O11/c1-5-12(24)28-11-8(22)18-10-6(21)7(16(2,3)4)17(18)9(23)13(25)30-15(17)31-20(18,14(26)29-10)19(5,11)27/h5-11,15,21-23,27H,1-4H3/t5-,6-,7+,8+,9+,10-,11-,15-,17?,18?,19-,20?/m1/s1
SMILES O=C1O[C@H]2[C@@]([C@@H]1C)(O)C13C4([C@H]2O)[C@H](OC3=O)[C@@H]([C@H](C24[C@@H](O1)OC(=O)[C@@H]2O)C(C)(C)C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   440.13 Volume:   391.921
?
Van der Waals volume.
Dense:   1.123 LogP:   0.949
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.421
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.07
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   27.0
TPSA:   169.05
?
Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   4.0 Rings:   6.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.234 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.213 Fsp3:   0.85
MCE-18:   160.541
?
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:   0.52 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.013
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.001
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.282 Promiscuous compounds:   0.503

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.339 MDCK Permeability:   -4.912
Pgp-inhibitor:   0.003 Pgp-substrate:   0.98
PAMPA:   0.999
?
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):   0.002
20% Bioavailability (F20%):   0.002 30% Bioavailability (F30%):   0.016
50% Bioavailability (F50%):   0.211

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.799
Plasma Protein Binding (PPB):   32.546% Volume Distribution (VD):   -0.111
Fu: 64.089%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.99
OATP1B3 inhibitor:   0.99 BCRP inhibitor:   0.001
BSEP inhibitor:   0.006

ADMET: Metabolism

CYP1A2-inhibitor:   0.004 CYP1A2-substrate:   0.649
CYP2C19-inhibitor:   0.774 CYP2C19-substrate:   0.474
CYP2C9-inhibitor:   0.005 CYP2C9-substrate:   0.093
CYP2D6-inhibitor:   0.102 CYP2D6-substrate:   0.504
CYP3A4-inhibitor:   0.569 CYP3A4-substrate:   0.416
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.179
HLM stability:   0.459
?
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):  1.826 Half-life (T1/2):  3.702

ADMET: Toxicity

hERG Blockers:  0.006 hERG Blockers (10um):  0.106
Human Hepatotoxicity (H-HT):  0.609 Drug-induced Liver Injury (DILI):  0.431
AMES Toxicity:  0.913 Rat Oral Acute Toxicity:  0.625
Maximum Recommended Daily Dose:  0.75 Skin Sensitization:  0.999
Carcinogencity:  0.693 Eye Corrosion:  0.003
Eye Irritation:  0.448 Respiratory Toxicity:  0.56
Drug-induced Neurotoxicity:  0.357 Ototoxicity:  0.67
Hematotoxicity:  0.861 Drug-induced Nephrotoxicity:  0.907
Genotoxicity:  0.949 RPMI-8226 Immunitoxicity:  0.278
A549 Cytotoxicity:  0.341 Hek293 Cytotoxicity:  0.195
BCF:   0.922
?
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:   3.495
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.177
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.574
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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
NPO26293 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. leaf n.a. DOI[10.1016/S0031-9422(01)00320-X]
NPO26293 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. leaf n.a. PMID[11738417]
NPO26293 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. fruit n.a. PMID[21462031]
NPO26293 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26293 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26293 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26293 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
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]

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
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 730.8 nM PubChem BioAssay data set
NPT48 Individual protein Lysine-specific demethylase 4D-like Homo sapiens Potency = 39810.7 nM PubChem BioAssay data set
NPT49 Individual protein DNA-(apurinic or apyrimidinic site) lyase Homo sapiens Potency n.a. 8912.5 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Potency n.a. 5011.9 nM PubChem BioAssay data set

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 NPC18433 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 NPC88890
0.6935 Remote Similarity NPC123070
0.6935 Remote Similarity NPC132304
0.6935 Remote Similarity NPC169089
0.5758 Remote Similarity NPC292803
0.5441 Remote Similarity NPC114365
0.5441 Remote Similarity NPC154962
0.5441 Remote Similarity NPC18044
0.5441 Remote Similarity NPC177518

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC18433 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
0.6935 Remote Similarity NPD4056 Clinical (unspecified phase)
0.6935 Remote 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