Natural Product: NPC291709

Natural Product IDNPC291709
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 [(1S,6S,7R,7As)-6-Acetyloxy-1-(3-Methylbutanoyloxy)Spiro[6,7A-Dihydro-1H-Cyclopenta[C]Pyran-7,2'-Oxirane]-4-Yl]Methyl 3-Methylbutanoate
IUPAC Name [(1S,6S,7R,7aS)-6-acetyloxy-1-(3-methylbutanoyloxy)spiro[6,7a-dihydro-1H-cyclopenta[c]pyran-7,2'-oxirane]-4-yl]methyl 3-methylbutanoate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL249657
PubChem CID 92275
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001549] Monoterpenoids
          • [CHEMONTID:0001565] Iridoids 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 XLACUABANMZLCJ-KVJIRVJXSA-N
Standard InCHI InChI=1S/C22H30O8/c1-12(2)6-18(24)26-9-15-10-27-21(30-19(25)7-13(3)4)20-16(15)8-17(29-14(5)23)22(20)11-28-22/h8,10,12-13,17,20-21H,6-7,9,11H2,1-5H3/t17-,20+,21-,22+/m0/s1
SMILES CC(CC(=O)OCC1=CO[C@H]([C@H]2C1=C[C@@H]([C@@]12CO1)OC(=O)C)OC(=O)CC(C)C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   422.19 Volume:   420.538
?
Van der Waals volume.
Dense:   1.004 LogP:   3.376
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.349
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.735
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The logarithm of aqueous solubility value.
Rotatable Bonds:   11.0 Rigid Bonds:   16.0
TPSA:   100.66
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Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.334 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.032 Fsp3:   0.682
MCE-18:   71.946
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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:   0.155 Fluc inhibitor:   0.0
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.599
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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:   0.292 Promiscuous compounds:   0.66

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.699 MDCK Permeability:   -4.638
Pgp-inhibitor:   0.002 Pgp-substrate:   0.165
PAMPA:   0.67
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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):   0.074
20% Bioavailability (F20%):   0.202 30% Bioavailability (F30%):   0.647
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.921 MRP1:   0.154
Plasma Protein Binding (PPB):   36.481% Volume Distribution (VD):   -0.165
Fu: 56.331%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.001
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   0.122 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   0.971 CYP2C19-substrate:   0.622
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.596
CYP3A4-inhibitor:   0.996 CYP3A4-substrate:   0.974
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   1.0
HLM stability:   0.963
?
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):  6.765 Half-life (T1/2):  0.764

ADMET: Toxicity

hERG Blockers:  0.116 hERG Blockers (10um):  0.429
Human Hepatotoxicity (H-HT):  0.62 Drug-induced Liver Injury (DILI):  0.847
AMES Toxicity:  0.852 Rat Oral Acute Toxicity:  0.606
Maximum Recommended Daily Dose:  0.793 Skin Sensitization:  0.972
Carcinogencity:  0.644 Eye Corrosion:  0.001
Eye Irritation:  0.238 Respiratory Toxicity:  0.439
Drug-induced Neurotoxicity:  0.473 Ototoxicity:  0.85
Hematotoxicity:  0.668 Drug-induced Nephrotoxicity:  0.929
Genotoxicity:  0.817 RPMI-8226 Immunitoxicity:  0.422
A549 Cytotoxicity:  0.09 Hek293 Cytotoxicity:  0.081
BCF:   0.91
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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:   3.636
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.615
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.056
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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
NPO33249 valeriana sorbifolia Species Caprifoliaceae Eukaryota n.a. n.a. n.a. PMID[18052324]
NPO29016 Valeriana jatamansi Species Caprifoliaceae Eukaryota n.a. n.a. n.a. PMID[19245261]
NPO29016 Valeriana jatamansi Species Caprifoliaceae Eukaryota n.a. n.a. n.a. PMID[20151678]
NPO29016 Valeriana jatamansi Species Caprifoliaceae Eukaryota n.a. n.a. n.a. PMID[20853876]
NPO29016 Valeriana jatamansi Species Caprifoliaceae Eukaryota n.a. n.a. n.a. PMID[35481430]
NPO29016 Valeriana jatamansi Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28211 Valeriana jatamansii Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28211 Valeriana jatamansii Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28211 Valeriana jatamansii Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28211 Valeriana jatamansii Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29016 Valeriana jatamansi Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29016 Valeriana jatamansi Species Caprifoliaceae 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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 3100.0 nM PMID[18052324]

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 NPC291709 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
0.8824 High Similarity NPC241407
0.7895 Intermediate Similarity NPC90819
0.7857 Intermediate Similarity NPC124181
0.7544 Intermediate Similarity NPC153559
0.6721 Remote Similarity NPC473307
0.5469 Remote Similarity NPC244878
0.541 Remote Similarity NPC478846
0.5246 Remote Similarity NPC66504
0.5152 Remote Similarity NPC151093

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC291709 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