Natural Product: NPC156057

Natural Product IDNPC156057
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Hamiltone A
IUPAC Name (2S)-6-hydroxy-5,7-dimethoxy-2-(4-methoxyphenyl)-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL512763
PubChem CID 44566483
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002592] 7-O-methylated flavonoids

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 JEEVVZXYEKPPCC-ZDUSSCGKSA-N
Standard InCHI InChI=1S/C18H18O6/c1-21-11-6-4-10(5-7-11)13-8-12(19)16-14(24-13)9-15(22-2)17(20)18(16)23-3/h4-7,9,13,20H,8H2,1-3H3/t13-/m0/s1
SMILES COc1ccc(cc1)[C@@H]1CC(=O)c2c(cc(c(c2OC)O)OC)O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   330.11 Volume:   328.501
?
Van der Waals volume.
Dense:   1.005 LogP:   2.747
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.919
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.029
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   74.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.928 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.777 Fsp3:   0.278
MCE-18:   57.13
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.275 Fluc inhibitor:   0.822
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.219
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.304
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.295 Promiscuous compounds:   0.1

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.962 MDCK Permeability:   -4.756
Pgp-inhibitor:   0.974 Pgp-substrate:   0.009
PAMPA:   0.01
?
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):   0.015
20% Bioavailability (F20%):   0.003 30% Bioavailability (F30%):   0.015
50% Bioavailability (F50%):   0.323

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.833
Plasma Protein Binding (PPB):   93.151% Volume Distribution (VD):   -0.545
Fu: 5.773%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.891
OATP1B3 inhibitor:   0.972 BCRP inhibitor:   0.902
BSEP inhibitor:   0.969

ADMET: Metabolism

CYP1A2-inhibitor:   0.917 CYP1A2-substrate:   0.826
CYP2C19-inhibitor:   0.889 CYP2C19-substrate:   0.862
CYP2C9-inhibitor:   0.931 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.535 CYP2D6-substrate:   0.294
CYP3A4-inhibitor:   0.693 CYP3A4-substrate:   0.636
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.921
HLM stability:   0.817
?
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):  7.431 Half-life (T1/2):  1.352

ADMET: Toxicity

hERG Blockers:  0.242 hERG Blockers (10um):  0.483
Human Hepatotoxicity (H-HT):  0.772 Drug-induced Liver Injury (DILI):  0.899
AMES Toxicity:  0.674 Rat Oral Acute Toxicity:  0.581
Maximum Recommended Daily Dose:  0.634 Skin Sensitization:  0.624
Carcinogencity:  0.632 Eye Corrosion:  0.09
Eye Irritation:  0.958 Respiratory Toxicity:  0.901
Drug-induced Neurotoxicity:  0.901 Ototoxicity:  0.377
Hematotoxicity:  0.506 Drug-induced Nephrotoxicity:  0.786
Genotoxicity:  0.664 RPMI-8226 Immunitoxicity:  0.174
A549 Cytotoxicity:  0.491 Hek293 Cytotoxicity:  0.381
BCF:   1.235
?
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:   3.697
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.415
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.474
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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
NPO24252 Uvaria hamiltonii Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[14552774]
NPO40124 Erythrina schliebenii Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[28112509]
NPO24252 Uvaria hamiltonii Species Annonaceae Eukaryota leaf and stem n.a. n.a. PMID[9584399]
NPO40124 Erythrina schliebenii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24252 Uvaria hamiltonii Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24252 Uvaria hamiltonii Species Annonaceae 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
NPT82 Cell line MDA-MB-231 Homo sapiens EC50 = 200600.0 nM PMID[28112509]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 20.0 ug.mL-1 PMID[9584399]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis MIC = 96900.0 nM PMID[28112509]
NPT2 Others Unspecified n.a. Activity = 88.0 % PMID[24583356]
NPT2 Others Unspecified n.a. Activity = 1.1 n.a. PMID[23927793]

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 NPC156057 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
0.6809 Remote Similarity NPC99854
0.66 Remote Similarity NPC188243
0.66 Remote Similarity NPC110228
0.64 Remote Similarity NPC135616
0.6154 Remote Similarity NPC6407
0.6154 Remote Similarity NPC545184
0.5714 Remote Similarity NPC599987
0.5636 Remote Similarity NPC274784
0.5636 Remote Similarity NPC20709
0.5556 Remote Similarity NPC611253
0.5472 Remote Similarity NPC265871
0.5472 Remote Similarity NPC205093
0.5455 Remote Similarity NPC20354
0.5455 Remote Similarity NPC162869
0.5439 Remote Similarity NPC469758
0.537 Remote Similarity NPC225153
0.537 Remote Similarity NPC479876
0.5263 Remote Similarity NPC210084
0.5179 Remote Similarity NPC150648
0.5172 Remote Similarity NPC18727
0.5172 Remote Similarity NPC474208
0.5172 Remote Similarity NPC601395
0.5098 Remote Similarity NPC228184
0.5088 Remote Similarity NPC296917
0.5088 Remote Similarity NPC329203
0.5088 Remote Similarity NPC222342
0.5088 Remote Similarity NPC170907

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC156057 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