Natural Product: NPC148000

Natural Product IDNPC148000
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Desacetyl-Beta-Cyclopyrethrosin
IUPAC Name (3aS,4R,4aS,8R,8aR,9aS)-4,8-dihydroxy-8a-methyl-3,5-dimethylidene-3a,4,4a,6,7,8,9,9a-octahydrobenzo[f][1]benzofuran-2-one
Synonyms Desacetyl-Beta-Cyclopyrethrosin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL468246
PubChem CID 21629647
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:0001772] Eudesmanolides, secoeudesmanolides, 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 XUTVRCGEUDNRBV-XFKURJONSA-N
Standard InCHI InChI=1S/C15H20O4/c1-7-4-5-10(16)15(3)6-9-11(13(17)12(7)15)8(2)14(18)19-9/h9-13,16-17H,1-2,4-6H2,3H3/t9-,10+,11+,12+,13-,15-/m0/s1
SMILES C=C1CC[C@H]([C@]2(C)C[C@H]3[C@@H](C(=C)C(=O)O3)[C@@H]([C@@H]12)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   264.14 Volume:   269.578
?
Van der Waals volume.
Dense:   0.98 LogP:   1.115
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.239
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.156
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   18.0
TPSA:   66.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.392 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.793 Fsp3:   0.667
MCE-18:   54.4
?
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:   0.505 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.199
?
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:   0.515 Promiscuous compounds:   0.275

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.158 MDCK Permeability:   -4.924
Pgp-inhibitor:   0.054 Pgp-substrate:   0.686
PAMPA:   0.947
?
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):   0.624
20% Bioavailability (F20%):   0.957 30% Bioavailability (F30%):   0.985
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.503 MRP1:   0.355
Plasma Protein Binding (PPB):   64.539% Volume Distribution (VD):   -0.063
Fu: 37.094%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.995
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.529
BSEP inhibitor:   0.679

ADMET: Metabolism

CYP1A2-inhibitor:   0.003 CYP1A2-substrate:   0.002
CYP2C19-inhibitor:   0.003 CYP2C19-substrate:   0.011
CYP2C9-inhibitor:   0.009 CYP2C9-substrate:   0.02
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.056
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.295
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.438
HLM stability:   0.454
?
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):  6.141 Half-life (T1/2):  2.349

ADMET: Toxicity

hERG Blockers:  0.021 hERG Blockers (10um):  0.149
Human Hepatotoxicity (H-HT):  0.734 Drug-induced Liver Injury (DILI):  0.839
AMES Toxicity:  0.651 Rat Oral Acute Toxicity:  0.199
Maximum Recommended Daily Dose:  0.325 Skin Sensitization:  0.95
Carcinogencity:  0.754 Eye Corrosion:  0.078
Eye Irritation:  0.911 Respiratory Toxicity:  0.241
Drug-induced Neurotoxicity:  0.298 Ototoxicity:  0.737
Hematotoxicity:  0.458 Drug-induced Nephrotoxicity:  0.815
Genotoxicity:  0.428 RPMI-8226 Immunitoxicity:  0.079
A549 Cytotoxicity:  0.252 Hek293 Cytotoxicity:  0.182
BCF:   0.37
?
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:   3.039
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.509
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.717
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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
NPO26031 Acacia auriculiformis Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/0031-9422(80)80226-3]
NPO23205 Anthemis altissima Species n.a. n.a. n.a. n.a. n.a. PMID[12762812]
NPO26536 Garcinia humilis Species Clusiaceae Eukaryota n.a. n.a. n.a. PMID[15844964]
NPO8759 Anthemis melanolepis Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[20112996]
NPO26268 Salvia aethiopis Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[36987013]
NPO26268 Salvia aethiopis Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[38611827]
NPO11310 Baorangia pseudocalopus Species Boletaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23205 Anthemis altissima Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO8759 Anthemis melanolepis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26454 Acacia oswaldii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26136 Abuta racemosa Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26031 Acacia auriculiformis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26431 Aplophyllum sieversii n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO26658 Commiphora dalzielii Species Burseraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26536 Garcinia humilis Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25745 Grindelia arenicola Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26783 Jurinea eriobasis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8746 Melaleuca triumphalis Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26379 Metrosideros umbellata Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26268 Salvia aethiopis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26981 Thunbergia laurifolia Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23205 Anthemis altissima Species n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO26431 Aplophyllum sieversii n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO26536 Garcinia humilis Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26268 Salvia aethiopis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11310 Baorangia pseudocalopus Species Boletaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8746 Melaleuca triumphalis Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26031 Acacia auriculiformis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23205 Anthemis altissima Species n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO26379 Metrosideros umbellata Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26783 Jurinea eriobasis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26981 Thunbergia laurifolia Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26658 Commiphora dalzielii Species Burseraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26136 Abuta racemosa Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26454 Acacia oswaldii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25745 Grindelia arenicola 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT395 Cell line SF-268 Homo sapiens GI50 = 42700.0 nM PMID[20112996]
NPT83 Cell line MCF7 Homo sapiens GI50 = 52300.0 nM PMID[20112996]
NPT397 Cell line NCI-H460 Homo sapiens GI50 = 69000.0 nM PMID[20112996]
NPT83 Cell line MCF7 Homo sapiens TGI = 64200.0 nM PMID[20112996]
NPT451 Organism Helicobacter pylori Helicobacter pylori MIC = 50.0 ug.mL-1 PMID[12762812]
NPT729 Organism Micrococcus luteus Micrococcus luteus MIC = 6.25 ug.mL-1 PMID[20112996]
NPT1190 Organism Salmonella enterica Salmonella enterica MIC = 25.0 ug.mL-1 PMID[20112996]
NPT3888 Organism Micrococcus flavus Micrococcus flavus MIC = 50.0 ug.mL-1 PMID[12762812]
NPT141 Organism Agrobacterium tumefaciens Agrobacterium tumefaciens MIC = 25.0 ug.mL-1 PMID[20112996]
NPT3729 Organism Pseudomonas tolaasii Pseudomonas tolaasii MIC = 25.0 ug.mL-1 PMID[20112996]
NPT20 Organism Candida albicans Candida albicans MIC = 25.0 ug.mL-1 PMID[20112996]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 50.0 ug.mL-1 PMID[12762812]
NPT19 Organism Escherichia coli Escherichia coli MIC = 50.0 ug.mL-1 PMID[12762812]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 0.625 ug.mL-1 PMID[20112996]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MIC = 25.0 ug.mL-1 PMID[20112996]
NPT19 Organism Escherichia coli Escherichia coli MIC = 25.0 ug.mL-1 PMID[20112996]
NPT314 Organism Bacillus cereus Bacillus cereus MIC = 50.0 ug.mL-1 PMID[12762812]
NPT314 Organism Bacillus cereus Bacillus cereus MIC = 6.25 ug.mL-1 PMID[20112996]

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 NPC148000 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 NPC469596
1.0 High Similarity NPC225474
0.6809 Remote Similarity NPC216478
0.6809 Remote Similarity NPC480113
0.6458 Remote Similarity NPC305029
0.625 Remote Similarity NPC93245
0.5294 Remote Similarity NPC228766
0.5294 Remote Similarity NPC277771
0.5192 Remote Similarity NPC85698
0.5192 Remote Similarity NPC185638
0.5192 Remote Similarity NPC607770
0.5091 Remote Similarity NPC474395

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC148000 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