Natural Product: NPC255406

Natural Product IDNPC255406
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ZRJBHWIHUMBLCN-JYXJEATCSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 44461111
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0001253] Quinolines and derivatives
        • [CHEMONTID:0000056] Quinolones and derivatives

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 ZRJBHWIHUMBLCN-JYXJEATCSA-N
Standard InCHI InChI=1S/C15H18N2O/c1-3-11-10-6-9(2)8-15(11,16)12-4-5-14(18)17-13(12)7-10/h3-6,10H,7-8,16H2,1-2H3,(H,17,18)/b11-3+/t10?,15-/m1/s1
SMILES C/C=C/1C2C=C(C)C[C@@]1(c1ccc(nc1C2)O)N

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   242.14 Volume:   259.928
?
Van der Waals volume.
Dense:   0.932 LogP:   2.728
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.307
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.255
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The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   16.0
TPSA:   59.14
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.687 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.149 Fsp3:   0.4
MCE-18:   60.857
?
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:   0.761 Fluc inhibitor:   0.004
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.069
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.108
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.021 Promiscuous compounds:   0.012

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.953 MDCK Permeability:   -4.776
Pgp-inhibitor:   0.001 Pgp-substrate:   0.208
PAMPA:   0.448
?
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):   0.014
20% Bioavailability (F20%):   0.556 30% Bioavailability (F30%):   0.796
50% Bioavailability (F50%):   0.936

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.068 MRP1:   0.953
Plasma Protein Binding (PPB):   91.628% Volume Distribution (VD):   0.221
Fu: 10.37%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.957
OATP1B3 inhibitor:   0.967 BCRP inhibitor:   0.002
BSEP inhibitor:   0.331

ADMET: Metabolism

CYP1A2-inhibitor:   0.908 CYP1A2-substrate:   0.035
CYP2C19-inhibitor:   0.724 CYP2C19-substrate:   0.006
CYP2C9-inhibitor:   0.027 CYP2C9-substrate:   0.041
CYP2D6-inhibitor:   0.968 CYP2D6-substrate:   0.131
CYP3A4-inhibitor:   0.937 CYP3A4-substrate:   0.584
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.293
HLM stability:   0.508
?
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):  9.413 Half-life (T1/2):  0.958

ADMET: Toxicity

hERG Blockers:  0.025 hERG Blockers (10um):  0.285
Human Hepatotoxicity (H-HT):  0.737 Drug-induced Liver Injury (DILI):  0.261
AMES Toxicity:  0.36 Rat Oral Acute Toxicity:  0.786
Maximum Recommended Daily Dose:  0.685 Skin Sensitization:  0.833
Carcinogencity:  0.437 Eye Corrosion:  0.001
Eye Irritation:  0.223 Respiratory Toxicity:  0.861
Drug-induced Neurotoxicity:  0.448 Ototoxicity:  0.458
Hematotoxicity:  0.322 Drug-induced Nephrotoxicity:  0.136
Genotoxicity:  0.988 RPMI-8226 Immunitoxicity:  0.073
A549 Cytotoxicity:  0.044 Hek293 Cytotoxicity:  0.314
BCF:   0.738
?
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:   3.408
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.778
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.127
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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
NPO14928 Huperzia serrata Species Lycopodiaceae Eukaryota n.a. n.a. n.a. PMID[12141864]
NPO28197 Huperzia selago Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28197 Huperzia selago Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14928 Huperzia serrata Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28197 Huperzia selago Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14928 Huperzia serrata Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14928 Huperzia serrata Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28197 Huperzia selago Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28197 Huperzia selago Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14928 Huperzia serrata Species Lycopodiaceae 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 NPC255406 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
1.0 High Similarity NPC47298
1.0 High Similarity NPC482954
0.7843 Intermediate Similarity NPC484634
0.7143 Intermediate Similarity NPC484625
0.6296 Remote Similarity NPC32028
0.5862 Remote Similarity NPC259545
0.569 Remote Similarity NPC484624
0.5333 Remote Similarity NPC484637
0.5312 Remote Similarity NPC232340
0.5254 Remote Similarity NPC126481

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC255406 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
1.0 High Similarity NPD1684 Approved
1.0 High Similarity NPD1685 Approved
0.5333 Remote Similarity NPD5497 Clinical (unspecified phase)

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