Natural Product: NPC226182

Natural Product IDNPC226182
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 HZEJNIAQUFJSBF-CMDGGOBGSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11110066
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003467] Linear 1,3-diarylpropanoids
        • [CHEMONTID:0001630] Chalcones and dihydrochalcones
          • [CHEMONTID:0003472] 2'-Hydroxychalcones

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 HZEJNIAQUFJSBF-CMDGGOBGSA-N
Standard InCHI InChI=1S/C20H18O4/c1-20(2)11-10-14-18(23)15(12-17(22)19(14)24-20)16(21)9-8-13-6-4-3-5-7-13/h3-12,22-23H,1-2H3/b9-8+
SMILES CC1(C)C=Cc2c(c(cc(c2O1)O)C(=O)/C=C/c1ccccc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   322.12 Volume:   340.24
?
Van der Waals volume.
Dense:   0.947 LogP:   4.231
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.755
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.802
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   19.0
TPSA:   66.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.505 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.725 Fsp3:   0.15
MCE-18:   39.652
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.996 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.817
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.924
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.68 Promiscuous compounds:   0.279

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.942 MDCK Permeability:   -4.733
Pgp-inhibitor:   0.991 Pgp-substrate:   0.001
PAMPA:   0.258
?
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):   0.007
20% Bioavailability (F20%):   0.627 30% Bioavailability (F30%):   0.942
50% Bioavailability (F50%):   0.925

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.05 MRP1:   0.019
Plasma Protein Binding (PPB):   98.745% Volume Distribution (VD):   -0.109
Fu: 0.937%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.986
OATP1B3 inhibitor:   0.989 BCRP inhibitor:   0.241
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.969
CYP2C9-inhibitor:   0.753 CYP2C9-substrate:   0.008
CYP2D6-inhibitor:   0.119 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.105
?
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):  10.982 Half-life (T1/2):  0.934

ADMET: Toxicity

hERG Blockers:  0.224 hERG Blockers (10um):  0.546
Human Hepatotoxicity (H-HT):  0.618 Drug-induced Liver Injury (DILI):  0.462
AMES Toxicity:  0.427 Rat Oral Acute Toxicity:  0.21
Maximum Recommended Daily Dose:  0.625 Skin Sensitization:  0.929
Carcinogencity:  0.211 Eye Corrosion:  0.019
Eye Irritation:  0.974 Respiratory Toxicity:  0.774
Drug-induced Neurotoxicity:  0.503 Ototoxicity:  0.206
Hematotoxicity:  0.146 Drug-induced Nephrotoxicity:  0.388
Genotoxicity:  0.238 RPMI-8226 Immunitoxicity:  0.108
A549 Cytotoxicity:  0.238 Hek293 Cytotoxicity:  0.549
BCF:   1.576
?
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:   4.705
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.143
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.717
?
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
NPO5885 Bathymodiolus thermophilus Species Mytilidae Eukaryota n.a. gill n.a. PMID[21222464]
NPO25533 Stellaster equestris Species Goniasteridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24229 Schoenus nigricans Species Cyperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25730 Prorhinotermes simplex Species Termitoidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25708 Erioderma phaeorhizum Species Pannariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25149 Centaurea arguta Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5885 Bathymodiolus thermophilus Species Mytilidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24691 Astragalus orbiculatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25758 Aspergillus amstelodami Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25422 Artemisia dracunculoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21669 Acacia sieberana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25628 Abrus pulchellus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24128 Cassinia longifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25052 Diphysa robinioides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25628 Abrus pulchellus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24691 Astragalus orbiculatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5885 Bathymodiolus thermophilus Species Mytilidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25730 Prorhinotermes simplex Species Termitoidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25052 Diphysa robinioides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24229 Schoenus nigricans Species Cyperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25708 Erioderma phaeorhizum Species Pannariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25422 Artemisia dracunculoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21669 Acacia sieberana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24128 Cassinia longifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25758 Aspergillus amstelodami Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25628 Abrus pulchellus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25149 Centaurea arguta Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25533 Stellaster equestris Species Goniasteridae 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

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 NPC226182 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
0.7091 Intermediate Similarity NPC305355
0.6061 Remote Similarity NPC488700
0.6 Remote Similarity NPC11561
0.6 Remote Similarity NPC209397
0.5833 Remote Similarity NPC475680
0.5833 Remote Similarity NPC156590
0.5797 Remote Similarity NPC488705
0.5735 Remote Similarity NPC488707
0.5588 Remote Similarity NPC488701
0.5441 Remote Similarity NPC488702
0.5429 Remote Similarity NPC237994
0.5352 Remote Similarity NPC488704
0.5303 Remote Similarity NPC234255
0.5238 Remote Similarity NPC284080
0.5211 Remote Similarity NPC488703
0.5156 Remote Similarity NPC118840
0.5143 Remote Similarity NPC278175
0.5143 Remote Similarity NPC257236
0.5143 Remote Similarity NPC488706
0.5091 Remote Similarity NPC609512
0.5088 Remote Similarity NPC64359
0.5072 Remote Similarity NPC6118

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC226182 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
0.5143 Remote Similarity NPD7410 Clinical (unspecified phase)

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