Natural Product: NPC600341

Natural Product IDNPC600341
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 WPQOVUJKYMOEFK-LBPRGKRZSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL5200087
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 WPQOVUJKYMOEFK-LBPRGKRZSA-N
Standard InCHI InChI=1S/C19H19NO5/c1-22-18-10-3-4-20-12-5-9-6-13-14(25-8-24-13)7-11(9)16(15(10)12)17(21)19(18)23-2/h6-7,12,20-21H,3-5,8H2,1-2H3/t12-/m0/s1
SMILES COc1c(O)c2c3c(c1OC)CCN[C@H]3Cc1cc3c(cc1-2)OCO3

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   341.13 Volume:   333.527
?
Van der Waals volume.
Dense:   1.023 LogP:   2.143
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.329
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.015
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   24.0
TPSA:   69.18
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   5.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.875 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.37 Fsp3:   0.368
MCE-18:   88.0
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.675 Fluc inhibitor:   0.303
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.603
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.277
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.443

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.142 MDCK Permeability:   -4.842
Pgp-inhibitor:   0.006 Pgp-substrate:   0.183
PAMPA:   0.126
?
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%):   0.09 30% Bioavailability (F30%):   0.069
50% Bioavailability (F50%):   0.903

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.91 MRP1:   0.991
Plasma Protein Binding (PPB):   88.411% Volume Distribution (VD):   -0.098
Fu: 10.293%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.957
OATP1B3 inhibitor:   0.99 BCRP inhibitor:   0.07
BSEP inhibitor:   0.839

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.008
CYP2C19-inhibitor:   0.995 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.842 CYP2C9-substrate:   0.983
CYP2D6-inhibitor:   0.998 CYP2D6-substrate:   0.602
CYP3A4-inhibitor:   0.565 CYP3A4-substrate:   0.71
CYP2B6-substrate:   0.858 CYP2C8-inhibitor:   0.0
HLM stability:   0.061
?
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):  3.5 Half-life (T1/2):  1.42

ADMET: Toxicity

hERG Blockers:  0.424 hERG Blockers (10um):  0.647
Human Hepatotoxicity (H-HT):  0.88 Drug-induced Liver Injury (DILI):  0.611
AMES Toxicity:  0.843 Rat Oral Acute Toxicity:  0.735
Maximum Recommended Daily Dose:  0.843 Skin Sensitization:  0.824
Carcinogencity:  0.584 Eye Corrosion:  0.001
Eye Irritation:  0.584 Respiratory Toxicity:  0.937
Drug-induced Neurotoxicity:  0.858 Ototoxicity:  0.677
Hematotoxicity:  0.448 Drug-induced Nephrotoxicity:  0.806
Genotoxicity:  0.821 RPMI-8226 Immunitoxicity:  0.132
A549 Cytotoxicity:  0.155 Hek293 Cytotoxicity:  0.502
BCF:   1.506
?
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:   3.96
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.924
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.822
?
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
NPO46410 Nectandra sinuata Genus Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT113 Cell line RAW264.7 Mus musculus IC50 = 62.0 ug.mL-1 PMID[34118719]
NPT28438 Unchecked Unchecked n.a. IC50 = 67000.0 nM PMID[34118719]
NPT28438 Unchecked Unchecked n.a. IC50 < 100000.0 nM PMID[34118719]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis MIC = 64.0 ug.mL-1 PMID[34118719]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis MIC = 64.0 ug.mL-1 PMID[28628823]

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 NPC600341 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
0.6406 Remote Similarity NPC173416
0.6 Remote Similarity NPC298008
0.6 Remote Similarity NPC610238
0.5781 Remote Similarity NPC204947
0.5588 Remote Similarity NPC6152
0.5417 Remote Similarity NPC186546
0.5342 Remote Similarity NPC602079
0.5205 Remote Similarity NPC155442
0.5205 Remote Similarity NPC312918
0.5072 Remote Similarity NPC609330

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC600341 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
NPD

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