Natural Product: NPC589581

Natural Product IDNPC589581
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Kakkatin
IUPAC Name 6-hydroxy-3-(4-hydroxyphenyl)-7-methoxy-chromen-4-one
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 UXQHNHMMYMGPAH-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H12O5/c1-20-15-7-14-11(6-13(15)18)16(19)12(8-21-14)9-2-4-10(17)5-3-9/h2-8,17-18H,1H3
SMILES COC1=CC2=C(C=C1O)C(=O)C(C1=CC=C(O)C=C1)=CO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   284.07 Volume:   282.482
?
Van der Waals volume.
Dense:   1.006 LogP:   1.872
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.071
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.707
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   79.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.756 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.168 Fsp3:   0.062
MCE-18:   17.0
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.447 Fluc inhibitor:   0.992
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.976
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.671
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.574 Promiscuous compounds:   0.744

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.885 MDCK Permeability:   -4.785
Pgp-inhibitor:   0.003 Pgp-substrate:   0.024
PAMPA:   0.981
?
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):   0.087
20% Bioavailability (F20%):   0.472 30% Bioavailability (F30%):   0.307
50% Bioavailability (F50%):   0.9

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.736
Plasma Protein Binding (PPB):   87.207% Volume Distribution (VD):   -0.308
Fu: 14.13%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.946
OATP1B3 inhibitor:   0.978 BCRP inhibitor:   0.392
BSEP inhibitor:   0.782

ADMET: Metabolism

CYP1A2-inhibitor:   0.995 CYP1A2-substrate:   0.993
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.897
CYP2C9-inhibitor:   0.732 CYP2C9-substrate:   0.986
CYP2D6-inhibitor:   0.995 CYP2D6-substrate:   0.408
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.99
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.001
?
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):  7.432 Half-life (T1/2):  1.328

ADMET: Toxicity

hERG Blockers:  0.163 hERG Blockers (10um):  0.599
Human Hepatotoxicity (H-HT):  0.479 Drug-induced Liver Injury (DILI):  0.548
AMES Toxicity:  0.512 Rat Oral Acute Toxicity:  0.547
Maximum Recommended Daily Dose:  0.707 Skin Sensitization:  0.499
Carcinogencity:  0.721 Eye Corrosion:  0.167
Eye Irritation:  0.984 Respiratory Toxicity:  0.726
Drug-induced Neurotoxicity:  0.462 Ototoxicity:  0.226
Hematotoxicity:  0.156 Drug-induced Nephrotoxicity:  0.2
Genotoxicity:  0.741 RPMI-8226 Immunitoxicity:  0.075
A549 Cytotoxicity:  0.239 Hek293 Cytotoxicity:  0.574
BCF:   1.035
?
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:   3.427
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.234
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.784
?
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
NPO62920 Streptomyces GW39/1530 Genus Streptomycetaceae Bacteria 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

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 NPC589581 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
0.8039 Intermediate Similarity NPC603503
0.7547 Intermediate Similarity NPC100971
0.75 Intermediate Similarity NPC605229
0.7222 Intermediate Similarity NPC181124
0.6429 Remote Similarity NPC269451
0.6415 Remote Similarity NPC218490
0.6316 Remote Similarity NPC216769
0.6316 Remote Similarity NPC162680
0.6316 Remote Similarity NPC303644
0.614 Remote Similarity NPC7013
0.6034 Remote Similarity NPC121522
0.6 Remote Similarity NPC139364
0.5926 Remote Similarity NPC234560
0.5862 Remote Similarity NPC10467
0.5862 Remote Similarity NPC131266
0.5763 Remote Similarity NPC209560
0.5763 Remote Similarity NPC490700
0.5738 Remote Similarity NPC80710
0.5714 Remote Similarity NPC62518
0.5667 Remote Similarity NPC181209
0.55 Remote Similarity NPC203747
0.5493 Remote Similarity NPC259070
0.5455 Remote Similarity NPC219917
0.5439 Remote Similarity NPC182428
0.5439 Remote Similarity NPC120924
0.5417 Remote Similarity NPC105511
0.541 Remote Similarity NPC483565
0.5397 Remote Similarity NPC285973
0.5397 Remote Similarity NPC254702
0.5397 Remote Similarity NPC109187
0.5397 Remote Similarity NPC114192
0.5397 Remote Similarity NPC134726
0.5373 Remote Similarity NPC611071
0.5333 Remote Similarity NPC256555
0.5323 Remote Similarity NPC12377
0.5263 Remote Similarity NPC125449
0.5263 Remote Similarity NPC39426
0.5246 Remote Similarity NPC245382
0.5246 Remote Similarity NPC69430
0.5246 Remote Similarity NPC609386
0.5238 Remote Similarity NPC487216
0.5238 Remote Similarity NPC100263
0.5167 Remote Similarity NPC295384
0.5161 Remote Similarity NPC487217
0.5156 Remote Similarity NPC200060
0.5152 Remote Similarity NPC260640
0.5147 Remote Similarity NPC168085
0.5139 Remote Similarity NPC605730
0.5085 Remote Similarity NPC195919
0.5082 Remote Similarity NPC116632
0.5082 Remote Similarity NPC35763
0.5082 Remote Similarity NPC333691
0.5079 Remote Similarity NPC139293
0.5079 Remote Similarity NPC264289
0.5075 Remote Similarity NPC97716
0.5068 Remote Similarity NPC211014

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC589581 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
0.5263 Remote Similarity NPD1510 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