Natural Product: NPC61274

Natural Product IDNPC61274
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 GHLJEZSMMHWXTR-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 14349486
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002591] 6-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 GHLJEZSMMHWXTR-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O4/c1-19-14-9-8-13-16(17(14)20-2)12(18)10-15(21-13)11-6-4-3-5-7-11/h3-10H,1-2H3
SMILES COc1ccc2c(c(=O)cc(c3ccccc3)o2)c1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   282.09 Volume:   290.988
?
Van der Waals volume.
Dense:   0.969 LogP:   3.047
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.935
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.945
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   48.67
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.738 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.985 Fsp3:   0.118
MCE-18:   16.0
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.161 Fluc inhibitor:   0.897
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.802
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.738
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.552 Promiscuous compounds:   0.634

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.648 MDCK Permeability:   -4.638
Pgp-inhibitor:   0.983 Pgp-substrate:   0.032
PAMPA:   0.07
?
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):   0.005
20% Bioavailability (F20%):   0.075 30% Bioavailability (F30%):   0.304
50% Bioavailability (F50%):   0.878

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.351 MRP1:   0.897
Plasma Protein Binding (PPB):   98.595% Volume Distribution (VD):   -0.127
Fu: 0.847%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.932
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.973
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.846 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.07 CYP2C19-substrate:   0.308
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.109
CYP2D6-inhibitor:   0.998 CYP2D6-substrate:   0.957
CYP3A4-inhibitor:   0.242 CYP3A4-substrate:   0.975
CYP2B6-substrate:   0.003 CYP2C8-inhibitor:   0.98
HLM stability:   0.707
?
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):  5.645 Half-life (T1/2):  1.462

ADMET: Toxicity

hERG Blockers:  0.149 hERG Blockers (10um):  0.492
Human Hepatotoxicity (H-HT):  0.494 Drug-induced Liver Injury (DILI):  0.896
AMES Toxicity:  0.552 Rat Oral Acute Toxicity:  0.458
Maximum Recommended Daily Dose:  0.571 Skin Sensitization:  0.466
Carcinogencity:  0.836 Eye Corrosion:  0.383
Eye Irritation:  0.974 Respiratory Toxicity:  0.683
Drug-induced Neurotoxicity:  0.324 Ototoxicity:  0.103
Hematotoxicity:  0.291 Drug-induced Nephrotoxicity:  0.156
Genotoxicity:  0.713 RPMI-8226 Immunitoxicity:  0.059
A549 Cytotoxicity:  0.113 Hek293 Cytotoxicity:  0.379
BCF:   1.729
?
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:   4.085
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.963
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.589
?
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
NPO23628 Imperata cylindrica Species Poaceae Eukaryota n.a. n.a. n.a. DOI[10.3390/plants9101397]
NPO24038 Casimiroa edulis Species Rutaceae Eukaryota n.a. seed n.a. PMID[10075120]
NPO7344 Spiraea prunifolia Species Rosaceae Eukaryota n.a. n.a. n.a. PMID[11473429]
NPO23628 Imperata cylindrica Species Poaceae Eukaryota n.a. n.a. n.a. PMID[16499335]
NPO24038 Casimiroa edulis Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[17228877]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. rhizome n.a. PMID[18484537]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. root n.a. PMID[18484537]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota rhizomes n.a. n.a. PMID[19615910]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[29323912]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. root n.a. PMID[731398]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. rhizome n.a. PMID[731398]
NPO23628 Imperata cylindrica Species Poaceae Eukaryota n.a. rhizome n.a. PMID[7714541]
NPO23628 Imperata cylindrica Species Poaceae Eukaryota n.a. n.a. n.a. PMID[7760071]
NPO23628 Imperata cylindrica Species Poaceae Eukaryota n.a. rhizome n.a. PMID[7798964]
NPO19895 Plectranthus hereroensis Species Lamiaceae Eukaryota Roots n.a. n.a. PMID[7931371]
NPO23628 Imperata cylindrica Species Poaceae Eukaryota n.a. n.a. n.a. PMID[7964801]
NPO23356 Ascodesmis sphaerospora Species Ascodesmidaceae Eukaryota n.a. n.a. n.a. PMID[9868168]
NPO23628 Imperata cylindrica Species Poaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23588 Ursinia anthemoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23490 Dalbergia monetaria Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23398 Caralluma russeliana Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24038 Casimiroa edulis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7344 Spiraea prunifolia Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24038 Casimiroa edulis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23628 Imperata cylindrica Species Poaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23588 Ursinia anthemoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23628 Imperata cylindrica Species Poaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24038 Casimiroa edulis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23628 Imperata cylindrica Species Poaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23628 Imperata cylindrica Species Poaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO23628 Imperata cylindrica Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9814 Lactarius fuliginosus Species Russulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23588 Ursinia anthemoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17492 Amomum reticulatum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23356 Ascodesmis sphaerospora Species Ascodesmidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19895 Plectranthus hereroensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23822 Polypodium aureum Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24396 Grosvenoria rimbachii n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO15572 Espeletiopsis purpurascens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23398 Caralluma russeliana Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24280 Helianthus californicus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24038 Casimiroa edulis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23490 Dalbergia monetaria Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7344 Spiraea prunifolia Species Rosaceae 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 NPC61274 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
0.7551 Intermediate Similarity NPC23955
0.7447 Intermediate Similarity NPC41721
0.7143 Intermediate Similarity NPC214919
0.7143 Intermediate Similarity NPC106461
0.66 Remote Similarity NPC607644
0.6415 Remote Similarity NPC609062
0.6364 Remote Similarity NPC292460
0.6154 Remote Similarity NPC278556
0.6038 Remote Similarity NPC14958
0.5926 Remote Similarity NPC601286
0.5849 Remote Similarity NPC284424
0.5818 Remote Similarity NPC194281
0.5636 Remote Similarity NPC293183
0.5614 Remote Similarity NPC148423
0.5556 Remote Similarity NPC602026
0.5536 Remote Similarity NPC215932
0.5536 Remote Similarity NPC239128
0.537 Remote Similarity NPC302408
0.5357 Remote Similarity NPC599976
0.5345 Remote Similarity NPC135303
0.5273 Remote Similarity NPC101294
0.5273 Remote Similarity NPC2771
0.5263 Remote Similarity NPC488084
0.5263 Remote Similarity NPC275722
0.5263 Remote Similarity NPC127447
0.5172 Remote Similarity NPC18260
0.5167 Remote Similarity NPC608258
0.5098 Remote Similarity NPC32298
0.5091 Remote Similarity NPC40818
0.5085 Remote Similarity NPC217186
0.5085 Remote Similarity NPC604569

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC61274 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