Natural Product: NPC215988

Natural Product IDNPC215988
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 AETACSMBICRTEP-SYYWLGBQSA-N
IUPAC Name n.a.
Synonyms (+)-N-Acetylparthenolidine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL519906
PubChem CID n.a.
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:0001771] Germacranolides 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 AETACSMBICRTEP-SYYWLGBQSA-N
Standard InCHI InChI=1S/C17H25NO4/c1-10-5-4-8-17(3)15(22-17)14-12(7-6-10)13(16(20)21-14)9-18-11(2)19/h5,12-15H,4,6-9H2,1-3H3,(H,18,19)/b10-5+/t12-,13-,14-,15-,17+/m0/s1
SMILES C/C/1=CCC[C@]2(C)[C@H]([C@@H]3[C@@H](CC1)[C@H](CN=C(C)O)C(=O)O3)O2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   307.18 Volume:   315.167
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Van der Waals volume.
Dense:   0.975 LogP:   2.149
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.909
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.565
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   71.42
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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:   0.28 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.171 Fsp3:   0.765
MCE-18:   49.4
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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:   0 PAINS Alert:   0
Colloidal aggregators:   0.38 Fluc inhibitor:   0.008
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.008
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.048
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.021 Promiscuous compounds:   0.548

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.336 MDCK Permeability:   -4.885
Pgp-inhibitor:   0.961 Pgp-substrate:   0.077
PAMPA:   0.05
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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):   0.019
20% Bioavailability (F20%):   0.132 30% Bioavailability (F30%):   0.414
50% Bioavailability (F50%):   0.759

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.794
Plasma Protein Binding (PPB):   66.906% Volume Distribution (VD):   -0.185
Fu: 29.704%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.034
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.113 CYP1A2-substrate:   0.002
CYP2C19-inhibitor:   0.98 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.988 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.695 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.81 CYP3A4-substrate:   0.002
CYP2B6-substrate:   0.003 CYP2C8-inhibitor:   0.087
HLM stability:   0.048
?
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):  7.212 Half-life (T1/2):  1.483

ADMET: Toxicity

hERG Blockers:  0.014 hERG Blockers (10um):  0.051
Human Hepatotoxicity (H-HT):  0.84 Drug-induced Liver Injury (DILI):  0.833
AMES Toxicity:  0.63 Rat Oral Acute Toxicity:  0.404
Maximum Recommended Daily Dose:  0.128 Skin Sensitization:  0.998
Carcinogencity:  0.809 Eye Corrosion:  0.048
Eye Irritation:  0.943 Respiratory Toxicity:  0.457
Drug-induced Neurotoxicity:  0.275 Ototoxicity:  0.358
Hematotoxicity:  0.513 Drug-induced Nephrotoxicity:  0.797
Genotoxicity:  0.439 RPMI-8226 Immunitoxicity:  0.017
A549 Cytotoxicity:  0.017 Hek293 Cytotoxicity:  0.095
BCF:   0.953
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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:   3.699
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.328
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.636
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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
NPO5710 Michelia rajaniana Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[3236012]
NPO5710 Michelia rajaniana Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5710 Michelia rajaniana Species Magnoliaceae 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
NPT81 Cell line A549 Homo sapiens ED50 > 100.0 ug ml-1 DrugMatrix in vivo data: Hematology
NPT83 Cell line MCF7 Homo sapiens ED50 > 100.0 ug ml-1 DrugMatrix in vivo data: Hematology
NPT139 Cell line HT-29 Homo sapiens ED50 > 100.0 ug ml-1 PMID[20619938]

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 NPC215988 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
0.6833 Remote Similarity NPC70235
0.6792 Remote Similarity NPC207188
0.6102 Remote Similarity NPC484396
0.5167 Remote Similarity NPC38468
0.5167 Remote Similarity NPC192678
0.5167 Remote Similarity NPC319795
0.5167 Remote Similarity NPC50362
0.5167 Remote Similarity NPC488056
0.5167 Remote Similarity NPC605079

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC215988 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
0.5167 Remote Similarity NPD1733 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