Natural Product: NPC105456

Natural Product IDNPC105456
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3R,5S-Sonnerlactone
IUPAC Name (3R,5S)-5,10,12-trihydroxy-3-methyl-3,4,5,6,7,8-hexahydro-2-benzoxecin-1-one
Synonyms 3R,5S-Sonnerlactone
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1084896
PubChem CID 46890202
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0000176] Benzoic acids and derivatives
          • [CHEMONTID:0001248] Hydroxybenzoic acid 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 MQAGIKOTEWULFX-SCZZXKLOSA-N
Standard InCHI InChI=1S/C14H18O5/c1-8-5-10(15)4-2-3-9-6-11(16)7-12(17)13(9)14(18)19-8/h6-8,10,15-17H,2-5H2,1H3/t8-,10+/m1/s1
SMILES C[C@@H]1C[C@H](CCCc2cc(cc(c2C(=O)O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   266.12 Volume:   266.993
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Van der Waals volume.
Dense:   0.997 LogP:   1.557
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.888
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.779
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The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   16.0
TPSA:   86.99
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Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.622 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.732 Fsp3:   0.5
MCE-18:   46.429
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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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.226 Fluc inhibitor:   0.066
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.234
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.18
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.228 Promiscuous compounds:   0.459

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.892 MDCK Permeability:   -4.824
Pgp-inhibitor:   0.22 Pgp-substrate:   0.594
PAMPA:   0.338
?
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):   0.002
20% Bioavailability (F20%):   0.371 30% Bioavailability (F30%):   0.792
50% Bioavailability (F50%):   0.937

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.028 MRP1:   0.891
Plasma Protein Binding (PPB):   89.449% Volume Distribution (VD):   -0.255
Fu: 7.733%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.989
OATP1B3 inhibitor:   0.985 BCRP inhibitor:   0.669
BSEP inhibitor:   0.814

ADMET: Metabolism

CYP1A2-inhibitor:   0.598 CYP1A2-substrate:   0.012
CYP2C19-inhibitor:   0.066 CYP2C19-substrate:   0.007
CYP2C9-inhibitor:   0.005 CYP2C9-substrate:   0.33
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.997
CYP3A4-inhibitor:   0.05 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.575
?
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):  7.828 Half-life (T1/2):  1.569

ADMET: Toxicity

hERG Blockers:  0.019 hERG Blockers (10um):  0.23
Human Hepatotoxicity (H-HT):  0.488 Drug-induced Liver Injury (DILI):  0.53
AMES Toxicity:  0.909 Rat Oral Acute Toxicity:  0.24
Maximum Recommended Daily Dose:  0.867 Skin Sensitization:  1.0
Carcinogencity:  0.87 Eye Corrosion:  0.326
Eye Irritation:  0.99 Respiratory Toxicity:  0.414
Drug-induced Neurotoxicity:  0.408 Ototoxicity:  0.173
Hematotoxicity:  0.067 Drug-induced Nephrotoxicity:  0.852
Genotoxicity:  0.79 RPMI-8226 Immunitoxicity:  0.089
A549 Cytotoxicity:  0.813 Hek293 Cytotoxicity:  0.469
BCF:   0.559
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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:   3.174
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.396
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.718
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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
NPO33319 zh6-b1 n.a. n.a. n.a. n.a. South China Sea n.a. PMID[20452765]

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. GI = 41.6 % PMID[20452765]

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 NPC105456 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 NPC139634
0.7091 Intermediate Similarity NPC212693
0.7091 Intermediate Similarity NPC94248
0.6604 Remote Similarity NPC70380
0.6429 Remote Similarity NPC608268
0.6207 Remote Similarity NPC487444
0.6034 Remote Similarity NPC191835
0.56 Remote Similarity NPC219892
0.56 Remote Similarity NPC235115
0.5556 Remote Similarity NPC221352
0.5231 Remote Similarity NPC257558
0.5179 Remote Similarity NPC609111
0.5161 Remote Similarity NPC764
0.5082 Remote Similarity NPC53649
0.5079 Remote Similarity NPC609495

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC105456 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