Natural Product: NPC470670

Natural Product IDNPC470670
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Empetrikarinol B
IUPAC Name 2-methyl-1-[(2R,3S)-3,5,7-trihydroxy-2-methyl-2-(4-methylpent-3-enyl)-3,4-dihydrochromen-8-yl]butan-1-one
Synonyms Empetrikarinol B
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2152494
PubChem CID 71458439
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0000350] Butyrophenones

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 OOUQAKUAWXZBEN-PTPQSVRFSA-N
Standard InCHI InChI=1S/C21H30O5/c1-6-13(4)19(25)18-16(23)11-15(22)14-10-17(24)21(5,26-20(14)18)9-7-8-12(2)3/h8,11,13,17,22-24H,6-7,9-10H2,1-5H3/t13?,17-,21+/m0/s1
SMILES CCC(C)C(=O)c1c(cc(c2C[C@@H]([C@@](C)(CCC=C(C)C)Oc12)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   362.21 Volume:   385.428
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Van der Waals volume.
Dense:   0.94 LogP:   4.161
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.484
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.512
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   13.0
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:   0.523 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.195 Fsp3:   0.571
MCE-18:   57.273
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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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.425 Fluc inhibitor:   0.01
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.573
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.414
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.277 Promiscuous compounds:   0.144

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.739 MDCK Permeability:   -4.658
Pgp-inhibitor:   0.52 Pgp-substrate:   0.12
PAMPA:   0.306
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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):   0.001
20% Bioavailability (F20%):   0.054 30% Bioavailability (F30%):   0.49
50% Bioavailability (F50%):   0.98

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.167 MRP1:   0.996
Plasma Protein Binding (PPB):   96.896% Volume Distribution (VD):   0.179
Fu: 2.886%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.935
OATP1B3 inhibitor:   0.948 BCRP inhibitor:   0.456
BSEP inhibitor:   0.995

ADMET: Metabolism

CYP1A2-inhibitor:   0.028 CYP1A2-substrate:   0.003
CYP2C19-inhibitor:   0.939 CYP2C19-substrate:   0.012
CYP2C9-inhibitor:   0.005 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.01 CYP2D6-substrate:   0.312
CYP3A4-inhibitor:   0.474 CYP3A4-substrate:   0.374
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.104
HLM stability:   0.159
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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):  4.735 Half-life (T1/2):  1.6

ADMET: Toxicity

hERG Blockers:  0.154 hERG Blockers (10um):  0.642
Human Hepatotoxicity (H-HT):  0.555 Drug-induced Liver Injury (DILI):  0.071
AMES Toxicity:  0.249 Rat Oral Acute Toxicity:  0.356
Maximum Recommended Daily Dose:  0.43 Skin Sensitization:  0.856
Carcinogencity:  0.385 Eye Corrosion:  0.014
Eye Irritation:  0.749 Respiratory Toxicity:  0.912
Drug-induced Neurotoxicity:  0.193 Ototoxicity:  0.509
Hematotoxicity:  0.224 Drug-induced Nephrotoxicity:  0.448
Genotoxicity:  0.016 RPMI-8226 Immunitoxicity:  0.158
A549 Cytotoxicity:  0.227 Hek293 Cytotoxicity:  0.378
BCF:   1.865
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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:   4.4
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.996
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.416
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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
NPO33078 hypericum empetrifolium Species Hypericaceae Eukaryota n.a. n.a. n.a. PMID[23030826]
NPO30921 Hypericum roeperianum Species Hypericaceae Eukaryota n.a. n.a. n.a. PMID[24930002]
NPO30921 Hypericum roeperianum Species Hypericaceae Eukaryota n.a. n.a. n.a. PMID[26358281]
NPO40851 Garcinia dauphinensis Species Clusiaceae Eukaryota Roots n.a. n.a. PMID[30354100]
NPO30921 Hypericum roeperianum Species Hypericaceae Eukaryota n.a. root n.a. PMID[8862040]
NPO40851 Garcinia dauphinensis Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30921 Hypericum roeperianum Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO33078 hypericum empetrifolium Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT306 Cell line PC-3 Homo sapiens GI < 20.0 % PMID[1791472]
NPT139 Cell line HT-29 Homo sapiens GI = 20.0 % PMID[1791472]
NPT179 Cell line A2780 Homo sapiens IC50 = 10000.0 nM PMID[30354100]
NPT25 Cell line MT4 Homo sapiens CC50 = 45000.0 nM PMID[23013292]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 18400.0 nM PMID[23030826]
NPT19 Organism Escherichia coli Escherichia coli MIC > 1.0 ug.mL-1 PMID[19904995]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 EC50 > 45000.0 nM PMID[22672802]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC > 1.0 ug.mL-1 PMID[26046820]
NPT175 Organism Enterococcus faecalis Enterococcus faecalis MIC > 1.0 ug.mL-1 Open TG-GATES in vivo data: Biochemistry
NPT530 Organism Caenorhabditis elegans Caenorhabditis elegans Activity = 0.7 % PMID[18077363]

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 NPC470670 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
0.9038 High Similarity NPC47388
0.9038 High Similarity NPC473133
0.6897 Remote Similarity NPC470672
0.65 Remote Similarity NPC18886
0.625 Remote Similarity NPC244577
0.6167 Remote Similarity NPC474487
0.597 Remote Similarity NPC477272
0.5968 Remote Similarity NPC470669
0.5714 Remote Similarity NPC610821
0.5312 Remote Similarity NPC470668
0.5303 Remote Similarity NPC470675
0.5077 Remote Similarity NPC470674
0.5065 Remote Similarity NPC78377

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC470670 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