Natural Product: NPC35751

Natural Product IDNPC35751
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Acetyljaspiferal E
IUPAC Name (3Z,3aS,5aR,6R,7R,9aR,9bS)-7-acetyloxy-3a,6,9a-trimethyl-2-oxo-3-[(E)-5-oxopent-3-en-2-ylidene]-1,4,5,5a,7,8,9,9b-octahydrocyclopenta[a]naphthalene-6-carboxylic acid
Synonyms Acetyljaspiferal E
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL391289
PubChem CID 44434369
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001549] Monoterpenoids

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 WHGWJEWDUBCQJM-MGYIBXFFSA-N
Standard InCHI InChI=1S/C24H32O6/c1-14(7-6-12-25)20-16(27)13-18-22(3)11-9-19(30-15(2)26)24(5,21(28)29)17(22)8-10-23(18,20)4/h6-7,12,17-19H,8-11,13H2,1-5H3,(H,28,29)/b7-6+,20-14+/t17-,18+,19-,22+,23+,24-/m1/s1
SMILES C/C(=C1/C(=O)C[C@H]2[C@@]3(C)CC[C@H]([C@@](C)([C@@H]3CC[C@]12C)C(=O)O)OC(=O)C)/C=C/C=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   416.22 Volume:   434.913
?
Van der Waals volume.
Dense:   0.957 LogP:   2.079
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.14
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.461
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   21.0
TPSA:   97.74
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.424 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.659 Fsp3:   0.667
MCE-18:   66.3
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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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.437 Fluc inhibitor:   0.096
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.061
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.012
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.535 Promiscuous compounds:   0.124

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.415 MDCK Permeability:   -5.04
Pgp-inhibitor:   0.573 Pgp-substrate:   0.023
PAMPA:   0.915
?
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):   0.03
20% Bioavailability (F20%):   0.286 30% Bioavailability (F30%):   0.301
50% Bioavailability (F50%):   0.764

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.968
Plasma Protein Binding (PPB):   90.511% Volume Distribution (VD):   -0.478
Fu: 8.703%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.986
OATP1B3 inhibitor:   0.947 BCRP inhibitor:   0.01
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.026
CYP2C19-inhibitor:   0.233 CYP2C19-substrate:   0.054
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.005
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.217
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   0.775
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.995
HLM stability:   0.144
?
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):  1.83 Half-life (T1/2):  1.099

ADMET: Toxicity

hERG Blockers:  0.007 hERG Blockers (10um):  0.017
Human Hepatotoxicity (H-HT):  0.565 Drug-induced Liver Injury (DILI):  0.759
AMES Toxicity:  0.534 Rat Oral Acute Toxicity:  0.37
Maximum Recommended Daily Dose:  0.199 Skin Sensitization:  0.985
Carcinogencity:  0.851 Eye Corrosion:  0.74
Eye Irritation:  0.795 Respiratory Toxicity:  0.574
Drug-induced Neurotoxicity:  0.024 Ototoxicity:  0.293
Hematotoxicity:  0.766 Drug-induced Nephrotoxicity:  0.957
Genotoxicity:  0.92 RPMI-8226 Immunitoxicity:  0.036
A549 Cytotoxicity:  0.024 Hek293 Cytotoxicity:  0.029
BCF:   0.713
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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:   3.827
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.622
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.957
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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
NPO28502 Rhabdastrella globostellata Species Ancorinidae Eukaryota n.a. n.a. n.a. PMID[11858759]
NPO28502 Rhabdastrella globostellata Species Ancorinidae Eukaryota n.a. n.a. n.a. PMID[16499318]
NPO28502 Rhabdastrella globostellata Species Ancorinidae Eukaryota n.a. n.a. n.a. PMID[16562838]
NPO28502 Rhabdastrella globostellata Species Ancorinidae Eukaryota n.a. n.a. n.a. PMID[17524651]
NPO28502 Rhabdastrella globostellata Species Ancorinidae Eukaryota n.a. n.a. n.a. PMID[20627740]
NPO28502 Rhabdastrella globostellata Species Ancorinidae Eukaryota n.a. n.a. n.a. PMID[20718449]
NPO28502 Rhabdastrella globostellata Species Ancorinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28502 Rhabdastrella globostellata Species Ancorinidae 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
NPT737 Cell line HUVEC Homo sapiens IC50 = 2200.0 nM PMID[12502332]
NPT111 Cell line K562 Homo sapiens IC50 = 32000.0 nM DOI[10.1021/np50028a014]
NPT737 Cell line HUVEC Homo sapiens Ratio IC50 = 13.0 n.a. PMID[20643902]
NPT111 Cell line K562 Homo sapiens Ratio IC50 = 15.0 n.a. PMID[20643902]
NPT737 Cell line HUVEC Homo sapiens Ratio IC50 = 14.0 n.a. PMID[25468043]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 28000.0 nM PMID[17524651]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 34000.0 nM PMID[17524651]

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 NPC35751 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
0.6806 Remote Similarity NPC475418
0.6301 Remote Similarity NPC72151
0.5325 Remote Similarity NPC318363
0.5256 Remote Similarity NPC329345
0.507 Remote Similarity NPC471901
0.5068 Remote Similarity NPC23621
0.5068 Remote Similarity NPC106425
0.5068 Remote Similarity NPC184006
0.5068 Remote Similarity NPC122324

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC35751 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