Natural Product: NPC305440

Natural Product IDNPC305440
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RBOXVHNMENFORY-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 3063
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0000058] Morphinans

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 RBOXVHNMENFORY-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H23NO3/c1-19-8-7-18-11-4-5-13(20)17(18)22-16-14(21-2)6-3-10(15(16)18)9-12(11)19/h3,6,11-13,17,20H,4-5,7-9H2,1-2H3
SMILES CN1CCC23C4CCC(C3Oc3c(ccc(CC14)c23)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   301.17 Volume:   306.56
?
Van der Waals volume.
Dense:   0.982 LogP:   1.489
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.183
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.855
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   22.0
TPSA:   41.93
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.858 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.017 Fsp3:   0.667
MCE-18:   126.0
?
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:   0.287 Fluc inhibitor:   0.082
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.114
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.065
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.007 Promiscuous compounds:   0.289

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.751 MDCK Permeability:   -4.864
Pgp-inhibitor:   0.035 Pgp-substrate:   0.582
PAMPA:   0.174
?
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):   0.02
20% Bioavailability (F20%):   0.175 30% Bioavailability (F30%):   0.342
50% Bioavailability (F50%):   0.938

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.961 MRP1:   0.95
Plasma Protein Binding (PPB):   31.578% Volume Distribution (VD):   0.318
Fu: 63.782%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.079
OATP1B3 inhibitor:   0.345 BCRP inhibitor:   0.313
BSEP inhibitor:   0.722

ADMET: Metabolism

CYP1A2-inhibitor:   0.008 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.811 CYP2C9-substrate:   0.026
CYP2D6-inhibitor:   0.966 CYP2D6-substrate:   0.003
CYP3A4-inhibitor:   0.707 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.867 CYP2C8-inhibitor:   0.0
HLM stability:   0.008
?
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):  13.854 Half-life (T1/2):  4.2

ADMET: Toxicity

hERG Blockers:  0.474 hERG Blockers (10um):  0.639
Human Hepatotoxicity (H-HT):  0.61 Drug-induced Liver Injury (DILI):  0.038
AMES Toxicity:  0.554 Rat Oral Acute Toxicity:  0.649
Maximum Recommended Daily Dose:  0.838 Skin Sensitization:  0.258
Carcinogencity:  0.573 Eye Corrosion:  0.0
Eye Irritation:  0.013 Respiratory Toxicity:  0.905
Drug-induced Neurotoxicity:  0.445 Ototoxicity:  0.904
Hematotoxicity:  0.111 Drug-induced Nephrotoxicity:  0.114
Genotoxicity:  0.257 RPMI-8226 Immunitoxicity:  0.044
A549 Cytotoxicity:  0.089 Hek293 Cytotoxicity:  0.533
BCF:   1.155
?
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:   3.648
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.376
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.513
?
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

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 NPC305440 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 NPC67346
0.6866 Remote Similarity NPC115906
0.6812 Remote Similarity NPC43069
0.6765 Remote Similarity NPC97086
0.5946 Remote Similarity NPC140577
0.5833 Remote Similarity NPC214629
0.5833 Remote Similarity NPC174783
0.5063 Remote Similarity NPC311781

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC305440 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 NPD3057 Phase 4
0.8636 High Similarity NPD3051 Approved
0.6866 Remote Similarity NPD2971 Phase 4
0.6812 Remote Similarity NPD2972 Phase 4
0.6812 Remote Similarity NPD4107 Pre-clinical
0.6528 Remote Similarity NPD2970 Approved
0.6351 Remote Similarity NPD2969 Approved
0.6316 Remote Similarity NPD2968 Approved
0.5946 Remote Similarity NPD3533 Pre-clinical
0.5366 Remote Similarity NPD5676 Phase 4
0.5063 Remote Similarity NPD4482 Phase 4

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