Natural Product: NPC479545

Natural Product IDNPC479545
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 FPRFNXQLWQOWED-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 23652247
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002586] O-methylated isoflavonoids
          • [CHEMONTID:0002606] 4'-O-methylated isoflavonoids

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 FPRFNXQLWQOWED-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H16O3/c1-18-15-6-3-11(4-7-15)13-8-12-2-5-14(17)9-16(12)19-10-13/h2-7,9,13,17H,8,10H2,1H3
SMILES COc1ccc(cc1)C1Cc2ccc(cc2OC1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   256.11 Volume:   270.175
?
Van der Waals volume.
Dense:   0.948 LogP:   3.167
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.213
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.257
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   17.0
TPSA:   38.69
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.897 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.516 Fsp3:   0.25
MCE-18:   49.5
?
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:   0.737 Fluc inhibitor:   0.873
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.033
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.314
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.569 Promiscuous compounds:   0.229

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.65 MDCK Permeability:   -4.664
Pgp-inhibitor:   0.188 Pgp-substrate:   0.111
PAMPA:   0.05
?
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):   0.008
20% Bioavailability (F20%):   0.437 30% Bioavailability (F30%):   0.321
50% Bioavailability (F50%):   0.948

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.314 MRP1:   0.386
Plasma Protein Binding (PPB):   92.764% Volume Distribution (VD):   0.06
Fu: 4.684%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.951
OATP1B3 inhibitor:   0.982 BCRP inhibitor:   0.583
BSEP inhibitor:   0.911

ADMET: Metabolism

CYP1A2-inhibitor:   0.982 CYP1A2-substrate:   0.597
CYP2C19-inhibitor:   0.983 CYP2C19-substrate:   0.827
CYP2C9-inhibitor:   0.51 CYP2C9-substrate:   0.677
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.863
CYP3A4-inhibitor:   0.933 CYP3A4-substrate:   0.105
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.112
HLM stability:   0.412
?
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):  8.272 Half-life (T1/2):  1.427

ADMET: Toxicity

hERG Blockers:  0.434 hERG Blockers (10um):  0.668
Human Hepatotoxicity (H-HT):  0.678 Drug-induced Liver Injury (DILI):  0.315
AMES Toxicity:  0.559 Rat Oral Acute Toxicity:  0.374
Maximum Recommended Daily Dose:  0.588 Skin Sensitization:  0.214
Carcinogencity:  0.722 Eye Corrosion:  0.029
Eye Irritation:  0.931 Respiratory Toxicity:  0.71
Drug-induced Neurotoxicity:  0.56 Ototoxicity:  0.504
Hematotoxicity:  0.246 Drug-induced Nephrotoxicity:  0.294
Genotoxicity:  0.229 RPMI-8226 Immunitoxicity:  0.05
A549 Cytotoxicity:  0.278 Hek293 Cytotoxicity:  0.654
BCF:   1.513
?
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:   4.037
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.178
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.64
?
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
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. n.a. PMID[24211545]
NPO12323 Bos taurus Species Bovidae Eukaryota Urine n.a. n.a. PMID[6330305]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. n.a. PMID[932730]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. Database[FooDB]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. Database[FooDB]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12323 Bos taurus Species Bovidae 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
NPT22906 Protein complex Urease subunit alpha/Urease subunit beta Helicobacter pylori (strain ATCC 700392 / 26695) (Campylobacterpylori) IC50 = 358000.0 nM PMID[23567958]
NPT2 Others Unspecified n.a. IC50 = 1500000.0 nM PMID[6330305]

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 NPC479545 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
0.7955 Intermediate Similarity NPC193364
0.7551 Intermediate Similarity NPC230479
0.7551 Intermediate Similarity NPC50315
0.7391 Intermediate Similarity NPC26879
0.72 Intermediate Similarity NPC482710
0.7143 Intermediate Similarity NPC479544
0.6939 Remote Similarity NPC479543
0.6731 Remote Similarity NPC173660
0.6604 Remote Similarity NPC265433
0.6604 Remote Similarity NPC270456
0.6604 Remote Similarity NPC162659
0.5849 Remote Similarity NPC202981
0.5849 Remote Similarity NPC488571
0.5645 Remote Similarity NPC293203
0.5556 Remote Similarity NPC475492
0.5556 Remote Similarity NPC283049
0.5517 Remote Similarity NPC132222

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC479545 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
0.7955 Intermediate Similarity NPD1610 Phase 2
0.5172 Remote Similarity NPD4908 Phase 1

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