Natural Product: NPC318674

Natural Product IDNPC318674
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 HGPQAWTZLJXCTC-OTMKDFPBSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5319560
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 HGPQAWTZLJXCTC-OTMKDFPBSA-N
Standard InCHI InChI=1S/C19H23NO3/c1-20-9-8-19-12-5-7-15(22-3)18(19)23-17-14(21-2)6-4-11(16(17)19)10-13(12)20/h4-7,12-13,15,18H,8-10H2,1-3H3/t12-,13?,15-,18?,19?/m0/s1
SMILES CN1CCC23C4C1CC5=C2C(=C(C=C5)OC)OC3C(C=C4)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   313.17 Volume:   321.219
?
Van der Waals volume.
Dense:   0.975 LogP:   1.534
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.421
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.195
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   22.0
TPSA:   30.93
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   5.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.783 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.214 Fsp3:   0.579
MCE-18:   122.4
?
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:   0.159 Fluc inhibitor:   0.16
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.08
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.1
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.032 Promiscuous compounds:   0.12

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.695 MDCK Permeability:   -4.719
Pgp-inhibitor:   0.13 Pgp-substrate:   0.463
PAMPA:   0.023
?
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):   0.001
20% Bioavailability (F20%):   0.032 30% Bioavailability (F30%):   0.029
50% Bioavailability (F50%):   0.243

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.998 MRP1:   0.828
Plasma Protein Binding (PPB):   19.789% Volume Distribution (VD):   0.482
Fu: 75.163%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.044
OATP1B3 inhibitor:   0.197 BCRP inhibitor:   0.106
BSEP inhibitor:   0.856

ADMET: Metabolism

CYP1A2-inhibitor:   0.969 CYP1A2-substrate:   0.012
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.995 CYP2C9-substrate:   0.031
CYP2D6-inhibitor:   0.994 CYP2D6-substrate:   0.154
CYP3A4-inhibitor:   0.812 CYP3A4-substrate:   0.009
CYP2B6-substrate:   1.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.472
?
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):  12.273 Half-life (T1/2):  4.196

ADMET: Toxicity

hERG Blockers:  0.286 hERG Blockers (10um):  0.496
Human Hepatotoxicity (H-HT):  0.55 Drug-induced Liver Injury (DILI):  0.131
AMES Toxicity:  0.559 Rat Oral Acute Toxicity:  0.637
Maximum Recommended Daily Dose:  0.629 Skin Sensitization:  0.4
Carcinogencity:  0.531 Eye Corrosion:  0.001
Eye Irritation:  0.203 Respiratory Toxicity:  0.889
Drug-induced Neurotoxicity:  0.663 Ototoxicity:  0.678
Hematotoxicity:  0.211 Drug-induced Nephrotoxicity:  0.234
Genotoxicity:  0.465 RPMI-8226 Immunitoxicity:  0.048
A549 Cytotoxicity:  0.059 Hek293 Cytotoxicity:  0.324
BCF:   1.776
?
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:   3.78
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.356
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.616
?
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
NPO31048 Papaver sommiferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]

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 NPC318674 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 NPC174783
0.7761 Intermediate Similarity NPC311781
0.7015 Intermediate Similarity NPC214629
0.6812 Remote Similarity NPC43069
0.6143 Remote Similarity NPC115906
0.5946 Remote Similarity NPC140577
0.5833 Remote Similarity NPC67346
0.5132 Remote Similarity NPC323443
0.5132 Remote Similarity NPC180756

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC318674 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
0.7761 Intermediate Similarity NPD4482 Phase 4
0.7647 Intermediate Similarity NPD4481 Phase 3
0.6812 Remote Similarity NPD2972 Phase 4
0.6528 Remote Similarity NPD2970 Approved
0.6351 Remote Similarity NPD2969 Approved
0.6338 Remote Similarity NPD4107 Pre-clinical
0.6143 Remote Similarity NPD2971 Phase 4
0.5946 Remote Similarity NPD3533 Pre-clinical
0.5833 Remote Similarity NPD3057 Phase 4
0.5366 Remote Similarity NPD5676 Phase 4
0.5309 Remote Similarity NPD2968 Approved
0.5185 Remote Similarity NPD3051 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