Natural Product: NPC65603

Natural Product IDNPC65603
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2-Desoxy-6-Epi-Parthemollin
IUPAC Name (3aS,6S,8aR)-6-methyl-3-methylidene-7-(3-oxobutyl)-4,5,6,8a-tetrahydro-3aH-cyclohepta[b]furan-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2206434
PubChem CID 14605949
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones

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 NLZBDTSRJVCTCF-QCZZGDTMSA-N
Standard InCHI InChI=1S/C15H20O3/c1-9-4-7-13-11(3)15(17)18-14(13)8-12(9)6-5-10(2)16/h8-9,13-14H,3-7H2,1-2H3/t9-,13-,14+/m0/s1
SMILES CC(=O)CCC1=C[C@H]2OC(=O)C(=C)[C@@H]2CC[C@@H]1C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   248.14 Volume:   266.708
?
Van der Waals volume.
Dense:   0.93 LogP:   2.432
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.344
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.035
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   14.0
TPSA:   43.37
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.438 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.103 Fsp3:   0.6
MCE-18:   31.417
?
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:   0.165 Fluc inhibitor:   0.018
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.068
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.016
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.903 Promiscuous compounds:   0.221

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.688 MDCK Permeability:   -4.539
Pgp-inhibitor:   0.943 Pgp-substrate:   0.099
PAMPA:   0.302
?
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):   0.005
20% Bioavailability (F20%):   0.335 30% Bioavailability (F30%):   0.783
50% Bioavailability (F50%):   0.935

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.008 MRP1:   0.698
Plasma Protein Binding (PPB):   92.9% Volume Distribution (VD):   0.125
Fu: 7.327%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.438
BSEP inhibitor:   0.994

ADMET: Metabolism

CYP1A2-inhibitor:   0.337 CYP1A2-substrate:   0.132
CYP2C19-inhibitor:   0.316 CYP2C19-substrate:   0.899
CYP2C9-inhibitor:   0.306 CYP2C9-substrate:   0.036
CYP2D6-inhibitor:   0.003 CYP2D6-substrate:   0.648
CYP3A4-inhibitor:   0.024 CYP3A4-substrate:   0.734
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.981
HLM stability:   0.932
?
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):  6.757 Half-life (T1/2):  1.048

ADMET: Toxicity

hERG Blockers:  0.026 hERG Blockers (10um):  0.23
Human Hepatotoxicity (H-HT):  0.803 Drug-induced Liver Injury (DILI):  0.846
AMES Toxicity:  0.805 Rat Oral Acute Toxicity:  0.322
Maximum Recommended Daily Dose:  0.73 Skin Sensitization:  0.996
Carcinogencity:  0.954 Eye Corrosion:  0.391
Eye Irritation:  0.962 Respiratory Toxicity:  0.678
Drug-induced Neurotoxicity:  0.608 Ototoxicity:  0.436
Hematotoxicity:  0.893 Drug-induced Nephrotoxicity:  0.88
Genotoxicity:  0.356 RPMI-8226 Immunitoxicity:  0.124
A549 Cytotoxicity:  0.287 Hek293 Cytotoxicity:  0.218
BCF:   0.68
?
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:   3.433
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.949
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.284
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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
NPO17612 Xanthium sibiricum Species Asteraceae Eukaryota Fruits n.a. n.a. PMID[26110443]
NPO17612 Xanthium sibiricum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17612 Xanthium sibiricum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17612 Xanthium sibiricum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17612 Xanthium sibiricum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO17612 Xanthium sibiricum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO17612 Xanthium sibiricum 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
NPT116 Cell line HL-60 Homo sapiens IC50 > 50000.0 nM PMID[25695368]
NPT189 Cell line Vero Chlorocebus aethiops TC50 = 19.2 uM PMID[22393119]
NPT616 Cell line MDCK Canis lupus familiaris TC50 = 19.3 uM PMID[26052978]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 70.9 % PMID[22985027]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 81.5 % PMID[22985027]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 72.0 % PMID[22985027]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 83.2 % PMID[22985027]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 50000.0 nM PMID[22985027]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 8500.0 nM PMID[26110443]
NPT3119 Organism Human coxsackievirus B3 Human coxsackievirus B3 IC50 = 6400.0 nM PMID[15387649]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 8600.0 nM PMID[26110443]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus Inhibition < 20.0 % PMID[18295489]





 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 NPC65603 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
0.6304 Remote Similarity NPC301477
0.6304 Remote Similarity NPC25684
0.6304 Remote Similarity NPC281949
0.617 Remote Similarity NPC483163
0.6042 Remote Similarity NPC483165
0.6042 Remote Similarity NPC483164
0.587 Remote Similarity NPC193351
0.587 Remote Similarity NPC226669
0.587 Remote Similarity NPC138408
0.58 Remote Similarity NPC483166
0.5652 Remote Similarity NPC235906
0.5435 Remote Similarity NPC58956
0.5435 Remote Similarity NPC163003
0.5435 Remote Similarity NPC295633
0.5435 Remote Similarity NPC269206
0.5185 Remote Similarity NPC173609
0.5102 Remote Similarity NPC140287

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC65603 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