Natural Product: NPC553393

Natural Product IDNPC553393
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Luteolin 4'-sulfate
IUPAC Name [4-(5,7-dihydroxy-4-oxo-chromen-2-yl)-2-hydroxy-phenyl] hydrogen sulfate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 MCJCSFGCQMESFL-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H10O9S/c16-8-4-10(18)15-11(19)6-13(23-14(15)5-8)7-1-2-12(9(17)3-7)24-25(20,21)22/h1-6,16-18H,(H,20,21,22)
SMILES O=C1C=C(C2=CC=C(OS(=O)(=O)O)C(O)=C2)OC2=CC(O)=CC(O)=C12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   366.0 Volume:   318.856
?
Van der Waals volume.
Dense:   1.148 LogP:   1.394
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.541
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.559
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   20.0
TPSA:   154.5
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.507 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.656 Fsp3:   0.0
MCE-18:   21.0
?
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:   0.564 Fluc inhibitor:   0.484
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.918
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.605
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.754 Promiscuous compounds:   0.347

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.754 MDCK Permeability:   -4.867
Pgp-inhibitor:   0.007 Pgp-substrate:   0.4
PAMPA:   0.75
?
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):   0.116
20% Bioavailability (F20%):   0.822 30% Bioavailability (F30%):   0.99
50% Bioavailability (F50%):   0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.929
Plasma Protein Binding (PPB):   98.481% Volume Distribution (VD):   -0.773
Fu: 1.424%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.428
OATP1B3 inhibitor:   0.957 BCRP inhibitor:   0.964
BSEP inhibitor:   0.293

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.001
HLM stability:   0.019
?
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):  2.27 Half-life (T1/2):  1.526

ADMET: Toxicity

hERG Blockers:  0.017 hERG Blockers (10um):  0.116
Human Hepatotoxicity (H-HT):  0.402 Drug-induced Liver Injury (DILI):  0.976
AMES Toxicity:  0.294 Rat Oral Acute Toxicity:  0.21
Maximum Recommended Daily Dose:  0.963 Skin Sensitization:  0.861
Carcinogencity:  0.434 Eye Corrosion:  0.875
Eye Irritation:  0.995 Respiratory Toxicity:  0.83
Drug-induced Neurotoxicity:  0.001 Ototoxicity:  0.071
Hematotoxicity:  0.044 Drug-induced Nephrotoxicity:  0.026
Genotoxicity:  0.996 RPMI-8226 Immunitoxicity:  0.025
A549 Cytotoxicity:  0.029 Hek293 Cytotoxicity:  0.393
BCF:   0.694
?
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:   3.143
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.362
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.065
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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
NPO163 Daucus carota Species Apiaceae Eukaryota n.a. n.a. DOI[10.1016/0045-6535(91)90110-Y]
NPO163 Daucus carota Species Apiaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.abb.2017.09.009]
NPO163 Daucus carota Species Apiaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.jfca.2004.07.004]
NPO163 Daucus carota Species Apiaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.jfca.2005.08.001]
NPO163 Daucus carota Species Apiaceae Eukaryota n.a. retail stores, supermarkets and market stalls in Forssa and in the Helsinki area 2003–2005 DOI[10.1016/j.jfca.2006.05.007]
NPO163 Daucus carota Species Apiaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0885-5765(05)80069-4]
NPO163 Daucus carota Species Apiaceae Eukaryota n.a. n.a. 1996-Sep PMID[10352947]
NPO163 Daucus carota Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[15877880]
NPO163 Daucus carota Species Apiaceae Eukaryota n.a. Northeastern Regional Plant Introduction Station at Geneva 1966, 1967, and 1968 crop seasons PMID[18460139]
NPO163 Daucus carota Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[18460139]
NPO163 Daucus carota Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[21800857]
NPO163 Daucus carota Species Apiaceae Eukaryota n.a. root n.a. PMID[21800857]
NPO163 Daucus carota Species Apiaceae Eukaryota n.a. exocarp n.a. PMID[21800857]
NPO163 Daucus carota Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[2831703]
NPO163 Daucus carota Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[6821187]
NPO163 Daucus carota Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO163 Daucus carota Species Apiaceae Eukaryota Roots n.a. Database[FooDB]
NPO163 Daucus carota Species Apiaceae Eukaryota Tissue Culture n.a. n.a. Database[FooDB]
NPO163 Daucus carota Species Apiaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO163 Daucus carota Species Apiaceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO163 Daucus carota Species Apiaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO163 Daucus carota Species Apiaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO163 Daucus carota Species Apiaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO163 Daucus carota Species Apiaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO163 Daucus carota Species Apiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO163 Daucus carota Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO163 Daucus carota Species Apiaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO163 Daucus carota Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO163 Daucus carota Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO163 Daucus carota Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO163 Daucus carota Species Apiaceae 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 NPC553393 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
0.6885 Remote Similarity NPC52005
0.6271 Remote Similarity NPC279121
0.6129 Remote Similarity NPC231772
0.6129 Remote Similarity NPC601901
0.5932 Remote Similarity NPC50898
0.5932 Remote Similarity NPC78540
0.5846 Remote Similarity NPC12200
0.5846 Remote Similarity NPC606638
0.5833 Remote Similarity NPC175013
0.5821 Remote Similarity NPC605587
0.575 Remote Similarity NPC600989
0.5625 Remote Similarity NPC62536
0.5625 Remote Similarity NPC120464
0.5625 Remote Similarity NPC483773
0.5588 Remote Similarity NPC605634
0.5571 Remote Similarity NPC112954
0.5522 Remote Similarity NPC183950
0.5417 Remote Similarity NPC34089
0.5417 Remote Similarity NPC196179
0.525 Remote Similarity NPC191306
0.5238 Remote Similarity NPC274121
0.5205 Remote Similarity NPC183
0.52 Remote Similarity NPC134796
0.52 Remote Similarity NPC604322
0.5156 Remote Similarity NPC213216
0.5077 Remote Similarity NPC610974
0.5075 Remote Similarity NPC256283

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC553393 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
0.6271 Remote Similarity NPD1511 Phase 2

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