Natural Product: NPC582000

Natural Product IDNPC582000
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Gossypetin 8,4'-dimethyl ether
IUPAC Name 3,5,7-trihydroxy-2-(3-hydroxy-4-methoxy-phenyl)-8-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 NJASMKIFEGXLSL-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O8/c1-23-11-4-3-7(5-8(11)18)15-14(22)13(21)12-9(19)6-10(20)16(24-2)17(12)25-15/h3-6,18-20,22H,1-2H3
SMILES COC1=CC=C(C2=C(O)C(=O)C3=C(O)C=C(O)C(OC)=C3O2)C=C1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   346.07 Volume:   326.149
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Van der Waals volume.
Dense:   1.061 LogP:   1.727
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.842
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.798
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   129.59
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Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.568 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.641 Fsp3:   0.118
MCE-18:   20.0
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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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.749 Fluc inhibitor:   0.342
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.899
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.493
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.428 Promiscuous compounds:   0.87

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.427 MDCK Permeability:   -4.85
Pgp-inhibitor:   0.3 Pgp-substrate:   0.151
PAMPA:   0.434
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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):   0.118
20% Bioavailability (F20%):   0.171 30% Bioavailability (F30%):   0.869
50% Bioavailability (F50%):   0.989

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.883
Plasma Protein Binding (PPB):   97.722% Volume Distribution (VD):   -0.679
Fu: 2.299%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.925
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.984
BSEP inhibitor:   0.55

ADMET: Metabolism

CYP1A2-inhibitor:   0.474 CYP1A2-substrate:   0.71
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.791
CYP2C9-inhibitor:   0.962 CYP2C9-substrate:   0.072
CYP2D6-inhibitor:   0.967 CYP2D6-substrate:   0.444
CYP3A4-inhibitor:   0.008 CYP3A4-substrate:   0.008
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.973
HLM stability:   0.991
?
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):  2.657 Half-life (T1/2):  1.996

ADMET: Toxicity

hERG Blockers:  0.049 hERG Blockers (10um):  0.441
Human Hepatotoxicity (H-HT):  0.384 Drug-induced Liver Injury (DILI):  0.721
AMES Toxicity:  0.536 Rat Oral Acute Toxicity:  0.45
Maximum Recommended Daily Dose:  0.467 Skin Sensitization:  0.611
Carcinogencity:  0.58 Eye Corrosion:  0.237
Eye Irritation:  0.987 Respiratory Toxicity:  0.827
Drug-induced Neurotoxicity:  0.066 Ototoxicity:  0.149
Hematotoxicity:  0.181 Drug-induced Nephrotoxicity:  0.121
Genotoxicity:  0.506 RPMI-8226 Immunitoxicity:  0.112
A549 Cytotoxicity:  0.332 Hek293 Cytotoxicity:  0.381
BCF:   0.873
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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:   3.544
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.382
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.78
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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
NPO7651 Citrus spp. Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[22472691]
NPO7651 Citrus spp. Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO64579 Primula vulgaris Species Primulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7651 Citrus spp. Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]

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 NPC582000 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
0.8235 Intermediate Similarity NPC201451
0.7455 Intermediate Similarity NPC610401
0.7273 Intermediate Similarity NPC54394
0.6842 Remote Similarity NPC189179
0.6667 Remote Similarity NPC200740
0.6271 Remote Similarity NPC93376
0.5938 Remote Similarity NPC130955
0.5932 Remote Similarity NPC86485
0.5862 Remote Similarity NPC600177
0.5833 Remote Similarity NPC82325
0.5833 Remote Similarity NPC55205
0.5763 Remote Similarity NPC50403
0.5763 Remote Similarity NPC241838
0.5738 Remote Similarity NPC75215
0.5738 Remote Similarity NPC52005
0.5645 Remote Similarity NPC482982
0.5574 Remote Similarity NPC204854
0.5574 Remote Similarity NPC146165
0.5574 Remote Similarity NPC159103
0.55 Remote Similarity NPC301123
0.55 Remote Similarity NPC176665
0.55 Remote Similarity NPC188203
0.5484 Remote Similarity NPC609179
0.5424 Remote Similarity NPC131624
0.5424 Remote Similarity NPC245546
0.5397 Remote Similarity NPC125062
0.5385 Remote Similarity NPC259411
0.5333 Remote Similarity NPC301323
0.5333 Remote Similarity NPC44079
0.5323 Remote Similarity NPC270620
0.5323 Remote Similarity NPC253634
0.5246 Remote Similarity NPC28274
0.5238 Remote Similarity NPC224137
0.5238 Remote Similarity NPC474520
0.5238 Remote Similarity NPC223579
0.5238 Remote Similarity NPC603112
0.5231 Remote Similarity NPC607815
0.5161 Remote Similarity NPC222830
0.5161 Remote Similarity NPC9609
0.5161 Remote Similarity NPC32420
0.5161 Remote Similarity NPC256283
0.5156 Remote Similarity NPC133953
0.5152 Remote Similarity NPC480464
0.5135 Remote Similarity NPC282987
0.5132 Remote Similarity NPC49344
0.5082 Remote Similarity NPC219330
0.5082 Remote Similarity NPC98661
0.5079 Remote Similarity NPC166753
0.5075 Remote Similarity NPC273538

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC582000 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
0.5075 Remote Similarity NPD4378 Phase 3

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