Natural Product: NPC476337

Natural Product IDNPC476337
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Cinerin B
IUPAC Name (1S,5S,6R,7R,8S)-8-hydroxy-5-methoxy-7-(7-methoxy-1,3-benzodioxol-5-yl)-6-methyl-3-prop-2-enylbicyclo[3.2.1]oct-3-en-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL570981
PubChem CID 45487095
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000296] Benzodioxoles

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 DMQHLPFSYZSVNQ-RFZQOIHJSA-N
Standard InCHI InChI=1S/C21H24O6/c1-5-6-12-9-21(25-4)11(2)16(17(18(12)22)20(21)23)13-7-14(24-3)19-15(8-13)26-10-27-19/h5,7-9,11,16-17,20,23H,1,6,10H2,2-4H3/t11-,16+,17-,20+,21-/m1/s1
SMILES C=CCC1=C[C@@]2(OC)[C@@H]([C@H]([C@H](C1=O)[C@@H]2O)c1cc(OC)c2c(c1)OCO2)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   372.16 Volume:   374.469
?
Van der Waals volume.
Dense:   0.994 LogP:   2.769
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.863
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.058
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   21.0
TPSA:   74.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.801 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.188 Fsp3:   0.476
MCE-18:   84.677
?
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:   0.156 Fluc inhibitor:   0.241
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.062
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.006
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.093 Promiscuous compounds:   0.336

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.766 MDCK Permeability:   -4.675
Pgp-inhibitor:   0.808 Pgp-substrate:   0.004
PAMPA:   0.108
?
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):   0.067
20% Bioavailability (F20%):   0.245 30% Bioavailability (F30%):   0.513
50% Bioavailability (F50%):   0.96

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.101 MRP1:   0.359
Plasma Protein Binding (PPB):   84.82% Volume Distribution (VD):   0.235
Fu: 17.289%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.471
BSEP inhibitor:   0.963

ADMET: Metabolism

CYP1A2-inhibitor:   0.192 CYP1A2-substrate:   0.974
CYP2C19-inhibitor:   0.846 CYP2C19-substrate:   0.88
CYP2C9-inhibitor:   0.121 CYP2C9-substrate:   0.949
CYP2D6-inhibitor:   0.088 CYP2D6-substrate:   0.997
CYP3A4-inhibitor:   0.622 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.008 CYP2C8-inhibitor:   0.995
HLM stability:   0.572
?
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):  5.39 Half-life (T1/2):  1.893

ADMET: Toxicity

hERG Blockers:  0.125 hERG Blockers (10um):  0.453
Human Hepatotoxicity (H-HT):  0.574 Drug-induced Liver Injury (DILI):  0.947
AMES Toxicity:  0.713 Rat Oral Acute Toxicity:  0.645
Maximum Recommended Daily Dose:  0.644 Skin Sensitization:  0.957
Carcinogencity:  0.728 Eye Corrosion:  0.0
Eye Irritation:  0.526 Respiratory Toxicity:  0.902
Drug-induced Neurotoxicity:  0.585 Ototoxicity:  0.705
Hematotoxicity:  0.748 Drug-induced Nephrotoxicity:  0.732
Genotoxicity:  0.985 RPMI-8226 Immunitoxicity:  0.3
A549 Cytotoxicity:  0.501 Hek293 Cytotoxicity:  0.584
BCF:   1.392
?
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:   3.755
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.298
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.632
?
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
NPO19526 Pleurothyrium cinereum Species Lauraceae Eukaryota leaves n.a. n.a. PMID[19548690]
NPO26326 Ocotea macrophylla Species Lauraceae Eukaryota leaves n.a. n.a. PMID[19880317]
NPO27964 Nectandra amazonum Species Lauraceae Eukaryota leaves n.a. n.a. PMID[19880317]
NPO19526 Pleurothyrium cinereum Species Lauraceae Eukaryota leaves n.a. n.a. PMID[19880317]
NPO26326 Ocotea macrophylla Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26326 Ocotea macrophylla Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27964 Nectandra amazonum Species Lauraceae 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
NPT324 Individual protein Cyclooxygenase-1 Ovis aries IC50 = 32500.0 nM DOI[10.6019/CHEMBL1201861]
NPT325 Individual protein Cyclooxygenase-2 Ovis aries IC50 = 215000.0 nM PMID[23985009]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1117 Organism Salmonella enterica subsp. enterica Salmonella enterica subsp. enterica GI < 30.0 % PMID[12113807]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 1500.0 nM PMID[19548690]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis GI = 19.5 % DrugMatrix in vitro pharmacology data
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis GI = 20.9 % DrugMatrix in vitro pharmacology data
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis GI = 13.9 % DrugMatrix in vitro pharmacology data
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 73.3 % PMID[19548690]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 1510.0 nM PMID[19880317]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 42800.0 nM PMID[19880317]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 999000.0 nM PMID[19880317]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus GI < 30.0 % PMID[10425119]
NPT175 Organism Enterococcus faecalis Enterococcus faecalis GI < 30.0 % PMID[16643040]
NPT19 Organism Escherichia coli Escherichia coli GI < 30.0 % PMID[12570385]
NPT2 Others Unspecified n.a. IC50 = 146000.0 nM PMID[17223562]
NPT2 Others Unspecified n.a. Ratio IC50 = 0.151 n.a. PMID[8496706]

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 NPC476337 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
0.8545 High Similarity NPC476335
0.8 Intermediate Similarity NPC476364
0.7333 Intermediate Similarity NPC476359
0.7333 Intermediate Similarity NPC476338
0.6515 Remote Similarity NPC476277
0.619 Remote Similarity NPC476362
0.597 Remote Similarity NPC476363
0.5846 Remote Similarity NPC28724
0.5714 Remote Similarity NPC476244
0.5373 Remote Similarity NPC476340
0.5067 Remote Similarity NPC484827

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC476337 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