Natural Product: NPC54996

Natural Product IDNPC54996
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Atractylenolide I
IUPAC Name (4aS,8aS)-3,8a-dimethyl-5-methylidene-4a,6,7,8-tetrahydro-4H-benzo[f][1]benzofuran-2-one
Synonyms Atractylenolide I
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL449520
PubChem CID 5321018
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0001634] Naphthofurans

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 ZTVSGQPHMUYCRS-SWLSCSKDSA-N
Standard InCHI InChI=1S/C15H18O2/c1-9-5-4-6-15(3)8-13-11(7-12(9)15)10(2)14(16)17-13/h8,12H,1,4-7H2,2-3H3/t12-,15+/m0/s1
SMILES C=C1CCC[C@]2(C)C=C3C(=C(C)C(=O)O3)C[C@@H]12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   230.13 Volume:   249.361
?
Van der Waals volume.
Dense:   0.923 LogP:   3.109
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.061
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.036
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   17.0
TPSA:   26.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.47 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.446 Fsp3:   0.533
MCE-18:   45.391
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.197 Fluc inhibitor:   0.064
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.284
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.117
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.93 Promiscuous compounds:   0.145

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.491 MDCK Permeability:   -4.535
Pgp-inhibitor:   0.044 Pgp-substrate:   0.0
PAMPA:   0.08
?
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%):   0.019 30% Bioavailability (F30%):   0.026
50% Bioavailability (F50%):   0.082

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.97 MRP1:   0.862
Plasma Protein Binding (PPB):   97.36% Volume Distribution (VD):   0.072
Fu: 2.647%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.954
OATP1B3 inhibitor:   0.957 BCRP inhibitor:   0.016
BSEP inhibitor:   0.847

ADMET: Metabolism

CYP1A2-inhibitor:   0.214 CYP1A2-substrate:   0.706
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.957 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.376 CYP2D6-substrate:   0.17
CYP3A4-inhibitor:   0.997 CYP3A4-substrate:   0.127
CYP2B6-substrate:   0.015 CYP2C8-inhibitor:   0.833
HLM stability:   0.998
?
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):  8.757 Half-life (T1/2):  1.256

ADMET: Toxicity

hERG Blockers:  0.03 hERG Blockers (10um):  0.3
Human Hepatotoxicity (H-HT):  0.653 Drug-induced Liver Injury (DILI):  0.717
AMES Toxicity:  0.412 Rat Oral Acute Toxicity:  0.376
Maximum Recommended Daily Dose:  0.627 Skin Sensitization:  0.995
Carcinogencity:  0.762 Eye Corrosion:  0.951
Eye Irritation:  0.994 Respiratory Toxicity:  0.565
Drug-induced Neurotoxicity:  0.53 Ototoxicity:  0.184
Hematotoxicity:  0.357 Drug-induced Nephrotoxicity:  0.597
Genotoxicity:  0.499 RPMI-8226 Immunitoxicity:  0.067
A549 Cytotoxicity:  0.052 Hek293 Cytotoxicity:  0.194
BCF:   1.862
?
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:   4.166
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.72
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.262
?
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
NPO26787 Chloranthus anhuiensis Species Chloranthaceae Eukaryota n.a. n.a. n.a. DOI[10.1021/np100063q]
NPO20902 Atractylodes macrocephala Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[17432574]
NPO16087 Atractylodes lancea Species Asteraceae Eukaryota n.a. rhizome n.a. PMID[18787781]
NPO16087 Atractylodes lancea Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[21302967]
NPO16087 Atractylodes lancea Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[27228227]
NPO26787 Chloranthus anhuiensis Species Chloranthaceae Eukaryota n.a. n.a. n.a. PMID[29775304]
NPO40789 Atractylodes rhizomes Species Asteraceae Eukaryota Rhizomes n.a. n.a. PMID[6418860]
NPO16087 Atractylodes lancea Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[9544564]
NPO26787 Chloranthus anhuiensis Species Chloranthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30858 Atractylodes japonica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12584 Atractylodes chinensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20902 Atractylodes macrocephala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16087 Atractylodes lancea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12584 Atractylodes chinensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16087 Atractylodes lancea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30858 Atractylodes japonica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20902 Atractylodes macrocephala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12584 Atractylodes chinensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20902 Atractylodes macrocephala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16087 Atractylodes lancea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16087 Atractylodes lancea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12584 Atractylodes chinensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20902 Atractylodes macrocephala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO30858 Atractylodes japonica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20902 Atractylodes macrocephala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO16087 Atractylodes lancea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO12584 Atractylodes chinensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO12584 Atractylodes chinensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20902 Atractylodes macrocephala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26787 Chloranthus anhuiensis Species Chloranthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16087 Atractylodes lancea Species Asteraceae 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
NPT30 Individual protein Cyclooxygenase-1 Homo sapiens IC50 > 200000.0 nM PMID[9544564]
NPT570 Individual protein Arachidonate 5-lipoxygenase Homo sapiens IC50 > 200000.0 nM PMID[9544564]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1135 Cell line Hepatocyte Rattus norvegicus Activity = 68.0 % PMID[6418860]
NPT1135 Cell line Hepatocyte Rattus norvegicus Activity = 107.0 % PMID[6418860]
NPT111 Cell line K562 Homo sapiens Activity > 50.0 % PMID[26988300]
NPT466 Cell line U-937 Homo sapiens FC = 2.0 n.a. PMID[26988300]
NPT15 Cell line Jurkat Homo sapiens FC = 2.0 n.a. PMID[26988300]
NPT111 Cell line K562 Homo sapiens Activity = 13.4 % PMID[26988300]
NPT111 Cell line K562 Homo sapiens Activity = 18.1 % PMID[26988300]
NPT466 Cell line U-937 Homo sapiens Activity = 50.0 % PMID[26988300]
NPT111 Cell line K562 Homo sapiens FC = 2.0 n.a. PMID[26988300]
NPT610 Others Molecular identity unknown n.a. Activity = 7.5 % PMID[26988300]
NPT610 Others Molecular identity unknown n.a. Activity = 20.3 % PMID[26988300]
NPT610 Others Molecular identity unknown n.a. Activity = 32.3 % PMID[26988300]
NPT610 Others Molecular identity unknown n.a. Activity > 50.0 % PMID[26988300]
NPT610 Others Molecular identity unknown n.a. Activity = 53.3 % PMID[26988300]
NPT610 Others Molecular identity unknown n.a. Activity = 84.3 % PMID[26988300]
NPT610 Others Molecular identity unknown n.a. Activity = 25.6 % PMID[26988300]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 4.23 ug.mL-1 PMID[26988300]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 14.91 ug.mL-1 PMID[26988300]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 24.11 ug.mL-1 PMID[26988300]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 24.44 ug.mL-1 PMID[26988300]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 37.63 ug.mL-1 PMID[26988300]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 44.67 ug.mL-1 PMID[26988300]

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 NPC54996 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
0.5625 Remote Similarity NPC215464

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC54996 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