Natural Product: NPC133888

Natural Product IDNPC133888
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2-Oacetyl-4-Epipulchellin
IUPAC Name [(3aS,5R,5aS,6S,8S,8aS,9aR)-8-hydroxy-5,8a-dimethyl-1-methylidene-2-oxo-4,5,5a,6,7,8,9,9a-octahydro-3aH-azuleno[6,5-b]furan-6-yl] acetate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1165403
PubChem CID 23242520
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones
          • [CHEMONTID:0001543] Sesquiterpene lactones
            • [CHEMONTID:0002046] Ambrosanolides and secoambrosanolides

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 JRTIKBMBXBPGNG-DOJYKCHUSA-N
Standard InCHI InChI=1S/C17H24O5/c1-8-5-12-11(9(2)16(20)22-12)7-17(4)14(19)6-13(15(8)17)21-10(3)18/h8,11-15,19H,2,5-7H2,1,3-4H3/t8-,11-,12+,13+,14+,15-,17-/m1/s1
SMILES CC(=O)O[C@H]1C[C@@H]([C@@]2([C@@H]1[C@H](C)C[C@H]1[C@H](C2)C(=C)C(=O)O1)C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   308.16 Volume:   312.961
?
Van der Waals volume.
Dense:   0.985 LogP:   0.841
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.034
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.877
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   72.83
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Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.591 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.709 Fsp3:   0.765
MCE-18:   56.0
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.539 Fluc inhibitor:   0.001
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.026
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.517 Promiscuous compounds:   0.631

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.131 MDCK Permeability:   -4.905
Pgp-inhibitor:   0.526 Pgp-substrate:   0.46
PAMPA:   0.908
?
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):   0.482
20% Bioavailability (F20%):   0.979 30% Bioavailability (F30%):   0.993
50% Bioavailability (F50%):   0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.09 MRP1:   0.71
Plasma Protein Binding (PPB):   67.395% Volume Distribution (VD):   -0.144
Fu: 33.551%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.094
BSEP inhibitor:   0.845

ADMET: Metabolism

CYP1A2-inhibitor:   0.01 CYP1A2-substrate:   0.002
CYP2C19-inhibitor:   0.425 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.002
CYP3A4-inhibitor:   0.323 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.002 CYP2C8-inhibitor:   0.69
HLM stability:   0.181
?
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):  4.407 Half-life (T1/2):  1.836

ADMET: Toxicity

hERG Blockers:  0.021 hERG Blockers (10um):  0.119
Human Hepatotoxicity (H-HT):  0.652 Drug-induced Liver Injury (DILI):  0.891
AMES Toxicity:  0.766 Rat Oral Acute Toxicity:  0.362
Maximum Recommended Daily Dose:  0.415 Skin Sensitization:  0.978
Carcinogencity:  0.736 Eye Corrosion:  0.244
Eye Irritation:  0.935 Respiratory Toxicity:  0.35
Drug-induced Neurotoxicity:  0.196 Ototoxicity:  0.582
Hematotoxicity:  0.643 Drug-induced Nephrotoxicity:  0.763
Genotoxicity:  0.449 RPMI-8226 Immunitoxicity:  0.083
A549 Cytotoxicity:  0.552 Hek293 Cytotoxicity:  0.224
BCF:   0.484
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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:   3.188
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.792
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.063
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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
NPO33493 inula lineariifolia Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[20515062]

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 = 250.0 nM PMID[24576210]

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 NPC133888 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 NPC171360
1.0 High Similarity NPC293001
1.0 High Similarity NPC239643
0.6531 Remote Similarity NPC35809
0.6471 Remote Similarity NPC27939
0.6471 Remote Similarity NPC57304
0.64 Remote Similarity NPC483168
0.64 Remote Similarity NPC56593
0.64 Remote Similarity NPC35959
0.5909 Remote Similarity NPC471382
0.5882 Remote Similarity NPC24728
0.5472 Remote Similarity NPC200237
0.5455 Remote Similarity NPC471150
0.5091 Remote Similarity NPC29821
0.5091 Remote Similarity NPC43777
0.5091 Remote Similarity NPC606153
0.5091 Remote Similarity NPC608282
0.5091 Remote Similarity NPC611056

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC133888 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