Natural Product: NPC478392

Natural Product IDNPC478392
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 KJUPGEKTXQYTSU-LKEKRHCZSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 97354635
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

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 KJUPGEKTXQYTSU-LKEKRHCZSA-N
Standard InCHI InChI=1S/C20H28O3/c1-13-6-9-16-19(2,3)10-5-11-20(16,4)15(13)8-7-14-12-17(21)23-18(14)22/h7-8,12,15-16,18,22H,1,5-6,9-11H2,2-4H3/b8-7+/t15-,16-,18+,20+/m0/s1
SMILES C=C1CC[C@H]2C(C)(C)CCC[C@]2(C)[C@H]1/C=C/C1=CC(=O)O[C@H]1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.2 Volume:   344.632
?
Van der Waals volume.
Dense:   0.918 LogP:   4.214
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.848
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.286
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   19.0
TPSA:   46.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.615 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.603 Fsp3:   0.65
MCE-18:   54.727
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.661 Fluc inhibitor:   0.266
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.013
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.004
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.57 Promiscuous compounds:   0.346

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.872 MDCK Permeability:   -4.76
Pgp-inhibitor:   0.157 Pgp-substrate:   0.003
PAMPA:   0.125
?
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):   0.0
20% Bioavailability (F20%):   0.004 30% Bioavailability (F30%):   0.16
50% Bioavailability (F50%):   0.961

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.005 MRP1:   0.093
Plasma Protein Binding (PPB):   98.441% Volume Distribution (VD):   0.371
Fu: 1.677%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.423
BSEP inhibitor:   0.99

ADMET: Metabolism

CYP1A2-inhibitor:   0.082 CYP1A2-substrate:   0.049
CYP2C19-inhibitor:   0.973 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.436 CYP2C9-substrate:   0.224
CYP2D6-inhibitor:   0.996 CYP2D6-substrate:   0.002
CYP3A4-inhibitor:   0.125 CYP3A4-substrate:   0.114
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.022
HLM stability:   0.992
?
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):  4.781 Half-life (T1/2):  0.937

ADMET: Toxicity

hERG Blockers:  0.084 hERG Blockers (10um):  0.423
Human Hepatotoxicity (H-HT):  0.522 Drug-induced Liver Injury (DILI):  0.352
AMES Toxicity:  0.529 Rat Oral Acute Toxicity:  0.531
Maximum Recommended Daily Dose:  0.869 Skin Sensitization:  0.841
Carcinogencity:  0.73 Eye Corrosion:  0.037
Eye Irritation:  0.85 Respiratory Toxicity:  0.756
Drug-induced Neurotoxicity:  0.548 Ototoxicity:  0.509
Hematotoxicity:  0.311 Drug-induced Nephrotoxicity:  0.761
Genotoxicity:  0.415 RPMI-8226 Immunitoxicity:  0.13
A549 Cytotoxicity:  0.116 Hek293 Cytotoxicity:  0.333
BCF:   2.21
?
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:   4.977
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.946
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.523
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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
NPO41076 Amomum villosum Species Zingiberaceae Eukaryota Rhizomes n.a. n.a. PMID[31710213]
NPO41076 Amomum villosum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT113 Cell line RAW264.7 Mus musculus IC50 = 2400.0 nM PMID[31710213]
NPT2 Others Unspecified n.a. Inhibition = 95.7 % PMID[31710213]
NPT2 Others Unspecified n.a. IC50 = 10000.0 nM PMID[31710213]
NPT2 Others Unspecified n.a. Ki = 9500.0 nM PMID[31710213]

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 NPC478392 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
0.9362 High Similarity NPC489285
0.6792 Remote Similarity NPC470255
0.6296 Remote Similarity NPC16321
0.625 Remote Similarity NPC472809
0.625 Remote Similarity NPC472810
0.5932 Remote Similarity NPC489288
0.5926 Remote Similarity NPC4509
0.5918 Remote Similarity NPC60772
0.5818 Remote Similarity NPC242069
0.5738 Remote Similarity NPC477720
0.5714 Remote Similarity NPC471654
0.5439 Remote Similarity NPC251528
0.5345 Remote Similarity NPC217394
0.5333 Remote Similarity NPC103290
0.5273 Remote Similarity NPC185587
0.5238 Remote Similarity NPC610810
0.5179 Remote Similarity NPC35655
0.5167 Remote Similarity NPC311070
0.5167 Remote Similarity NPC475709

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC478392 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