Natural Product: NPC126859

Natural Product IDNPC126859
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ZQHYKVKNPWDQSL-KNXBSLHKSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL316632
PubChem CID 443405
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0004131] 6,7-benzomorphans
        • [CHEMONTID:0004823] 2,6-dimethyl-3-benzazocines

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 ZQHYKVKNPWDQSL-KNXBSLHKSA-N
Standard InCHI InChI=1S/C22H27NO/c1-16-21-14-18-8-9-19(24)15-20(18)22(16,2)11-13-23(21)12-10-17-6-4-3-5-7-17/h3-9,15-16,21,24H,10-14H2,1-2H3/t16-,21+,22+/m0/s1
SMILES C[C@H]1[C@H]2Cc3ccc(cc3[C@]1(C)CCN2CCc1ccccc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   321.21 Volume:   358.811
?
Van der Waals volume.
Dense:   0.895 LogP:   3.581
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.231
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.119
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   21.0
TPSA:   23.47
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.917 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.909 Fsp3:   0.455
MCE-18:   74.25
?
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:   0.566 Fluc inhibitor:   0.007
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.065
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.17
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.06

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.731 MDCK Permeability:   -4.603
Pgp-inhibitor:   0.905 Pgp-substrate:   0.998
PAMPA:   0.008
?
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):   0.0
20% Bioavailability (F20%):   0.995 30% Bioavailability (F30%):   0.973
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   1.0 MRP1:   0.945
Plasma Protein Binding (PPB):   90.553% Volume Distribution (VD):   0.571
Fu: 6.384%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.056
OATP1B3 inhibitor:   0.01 BCRP inhibitor:   0.197
BSEP inhibitor:   0.994

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.093
CYP2C19-inhibitor:   0.899 CYP2C19-substrate:   0.03
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.942
CYP2D6-inhibitor:   0.824 CYP2D6-substrate:   0.008
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.053
HLM stability:   0.025
?
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):  18.035 Half-life (T1/2):  1.959

ADMET: Toxicity

hERG Blockers:  0.829 hERG Blockers (10um):  0.872
Human Hepatotoxicity (H-HT):  0.683 Drug-induced Liver Injury (DILI):  0.031
AMES Toxicity:  0.376 Rat Oral Acute Toxicity:  0.447
Maximum Recommended Daily Dose:  0.781 Skin Sensitization:  0.968
Carcinogencity:  0.187 Eye Corrosion:  0.021
Eye Irritation:  0.297 Respiratory Toxicity:  0.916
Drug-induced Neurotoxicity:  0.866 Ototoxicity:  0.545
Hematotoxicity:  0.203 Drug-induced Nephrotoxicity:  0.333
Genotoxicity:  0.521 RPMI-8226 Immunitoxicity:  0.046
A549 Cytotoxicity:  0.273 Hek293 Cytotoxicity:  0.76
BCF:   1.365
?
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:   3.935
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.076
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.626
?
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
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. DOI[10.1042/BA20020118]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. DOI[10.1556/abot.45.2003.3-4.15]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[15019787]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[22029392]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[23517479]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[37685099]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota Latex Exudate n.a. n.a. Database[FooDB]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. Database[FooDB]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. Database[FooDB]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO9498 Papaver somniferum Species Papaveraceae 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
NPT1069 Individual protein Mu opioid receptor Rattus norvegicus Ki = 0.2 nM PMID[1322987]
NPT145 Individual protein Mu opioid receptor Homo sapiens Ki = 61.7 nM PMID[35961067]
NPT1070 Individual protein Sigma-1 receptor Cavia porcellus Ki = 0.2 nM PMID[35961067]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Ki = 61.7 nM PMID[1322987]
NPT2 Others Unspecified n.a. Ki = 1880.0 nM PMID[1322987]
NPT2 Others Unspecified n.a. Ratio = 30.5 n.a. PMID[1322987]

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 NPC126859 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 NPC259665
1.0 High Similarity NPC89769
0.6949 Remote Similarity NPC66177
0.6949 Remote Similarity NPC268763
0.6949 Remote Similarity NPC310909
0.6949 Remote Similarity NPC8305

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC126859 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 NPD5156 Phase 4
0.9811 High Similarity NPD5155 Approved
0.6949 Remote Similarity NPD3637 Approved
0.6833 Remote Similarity NPD3636 Approved
0.6029 Remote Similarity NPD3635 Approved

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