Natural Product: NPC603094

Natural Product IDNPC603094
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 QCXAJQVDUHKDEL-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL307856
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002596] 4'-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 QCXAJQVDUHKDEL-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O5/c1-20-16-8-11(9-17(21-2)18(16)22-3)15-10-13(19)12-6-4-5-7-14(12)23-15/h4-10H,1-3H3
SMILES COc1cc(-c2cc(=O)c3ccccc3o2)cc(OC)c1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   312.1 Volume:   317.074
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Van der Waals volume.
Dense:   0.984 LogP:   2.502
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.798
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.128
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   57.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   5.0

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:   2.001 Fsp3:   0.167
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.078 Fluc inhibitor:   0.744
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.944
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.574
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.402 Promiscuous compounds:   0.62

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.668 MDCK Permeability:   -4.724
Pgp-inhibitor:   0.982 Pgp-substrate:   0.096
PAMPA:   0.095
?
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):   0.009
20% Bioavailability (F20%):   0.098 30% Bioavailability (F30%):   0.117
50% Bioavailability (F50%):   0.875

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.097 MRP1:   0.943
Plasma Protein Binding (PPB):   98.299% Volume Distribution (VD):   -0.201
Fu: 1.32%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.98
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.998
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.702 CYP1A2-substrate:   0.984
CYP2C19-inhibitor:   0.836 CYP2C19-substrate:   0.871
CYP2C9-inhibitor:   0.985 CYP2C9-substrate:   0.062
CYP2D6-inhibitor:   0.967 CYP2D6-substrate:   0.997
CYP3A4-inhibitor:   0.659 CYP3A4-substrate:   0.96
CYP2B6-substrate:   0.002 CYP2C8-inhibitor:   0.981
HLM stability:   0.566
?
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):  4.681 Half-life (T1/2):  1.27

ADMET: Toxicity

hERG Blockers:  0.123 hERG Blockers (10um):  0.479
Human Hepatotoxicity (H-HT):  0.448 Drug-induced Liver Injury (DILI):  0.778
AMES Toxicity:  0.465 Rat Oral Acute Toxicity:  0.383
Maximum Recommended Daily Dose:  0.52 Skin Sensitization:  0.427
Carcinogencity:  0.761 Eye Corrosion:  0.635
Eye Irritation:  0.974 Respiratory Toxicity:  0.696
Drug-induced Neurotoxicity:  0.454 Ototoxicity:  0.13
Hematotoxicity:  0.37 Drug-induced Nephrotoxicity:  0.188
Genotoxicity:  0.632 RPMI-8226 Immunitoxicity:  0.086
A549 Cytotoxicity:  0.12 Hek293 Cytotoxicity:  0.349
BCF:   1.451
?
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:   3.863
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.605
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.298
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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
NPO29219 Primula veris Species Primulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29219 Primula veris Species Primulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29219 Primula veris Species Primulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29219 Primula veris Species Primulaceae 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
NPT13 Individual protein Tyrosine-protein kinase LCK Homo sapiens IC50 > 2000000.0 nM PMID[1995903]
NPT1044 Individual protein DNA topoisomerase II alpha Homo sapiens Activity n.a. n.a. n.a. PMID[27343852]
NPT1044 Individual protein DNA topoisomerase II alpha Homo sapiens Inhibition n.a. n.a. % PMID[27343852]
NPT13 Individual protein Tyrosine-protein kinase LCK Homo sapiens IC50 > 800.0 ug.mL-1 PMID[1479375]
NPT30108 Protein complex group Tubulin Homo sapiens IC50 > 40000.0 nM PMID[9632366]
NPT29454 Single protein Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 Homo sapiens Inhibition = 4.514 % PMID[38318365]
NPT30108 Protein complex group Tubulin Homo sapiens Inhibition = 0.0 % PMID[9632366]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT517 Cell line Panel NCI-60 (60 carcinoma cell lines) Homo sapiens GI50 = 18000.0 nM PMID[9632366]
NPT28833 No target No relevant target n.a. EC50 = 71.66 ug.mL-1 PMID[33259925]

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 NPC603094 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
0.7872 Intermediate Similarity NPC483772
0.7755 Intermediate Similarity NPC77955
0.74 Intermediate Similarity NPC483774
0.7143 Intermediate Similarity NPC2771
0.7059 Intermediate Similarity NPC608264
0.6735 Remote Similarity NPC603362
0.6383 Remote Similarity NPC32298
0.6226 Remote Similarity NPC608669
0.6154 Remote Similarity NPC136278
0.5962 Remote Similarity NPC302408
0.5893 Remote Similarity NPC480173
0.5769 Remote Similarity NPC22783
0.5769 Remote Similarity NPC196034
0.5741 Remote Similarity NPC29536
0.5636 Remote Similarity NPC75279
0.5536 Remote Similarity NPC113089
0.5472 Remote Similarity NPC283002
0.5439 Remote Similarity NPC33265
0.5439 Remote Similarity NPC62536
0.537 Remote Similarity NPC607644
0.5357 Remote Similarity NPC599976
0.5273 Remote Similarity NPC284424
0.5179 Remote Similarity NPC333230
0.5167 Remote Similarity NPC604422
0.5091 Remote Similarity NPC193805
0.5091 Remote Similarity NPC604293
0.5088 Remote Similarity NPC250822

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC603094 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