Natural Product: NPC206681

Natural Product IDNPC206681
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 WGYGSZOQGYRGIP-YKNYVSNTSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 10334796
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000218] Pyrrolidines
        • [CHEMONTID:0002336] Phenylpyrrolidines

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 WGYGSZOQGYRGIP-YKNYVSNTSA-N
Standard InCHI InChI=1S/C18H19NO3/c1-19-15(16(20)13-10-6-3-7-11-13)14(17(21)18(19)22)12-8-4-2-5-9-12/h2-11,14-17,20-21H,1H3/t14-,15-,16?,17+/m1/s1
SMILES CN1[C@H]([C@@H](c2ccccc2)[C@@H](C1=O)O)C(c1ccccc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   297.14 Volume:   313.127
?
Van der Waals volume.
Dense:   0.949 LogP:   1.303
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.329
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.05
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   60.77
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.906 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.47 Fsp3:   0.278
MCE-18:   55.435
?
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:   0.381 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.062
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.169
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.096 Promiscuous compounds:   0.005

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.909 MDCK Permeability:   -4.758
Pgp-inhibitor:   0.134 Pgp-substrate:   0.559
PAMPA:   0.62
?
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):   0.045
20% Bioavailability (F20%):   0.256 30% Bioavailability (F30%):   0.979
50% Bioavailability (F50%):   0.909

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.62 MRP1:   0.799
Plasma Protein Binding (PPB):   61.122% Volume Distribution (VD):   0.292
Fu: 34.175%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.868
OATP1B3 inhibitor:   0.861 BCRP inhibitor:   0.003
BSEP inhibitor:   0.232

ADMET: Metabolism

CYP1A2-inhibitor:   0.019 CYP1A2-substrate:   0.026
CYP2C19-inhibitor:   0.078 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.011 CYP2C9-substrate:   0.458
CYP2D6-inhibitor:   0.028 CYP2D6-substrate:   0.008
CYP3A4-inhibitor:   0.942 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.025
HLM stability:   0.166
?
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):  5.19 Half-life (T1/2):  2.514

ADMET: Toxicity

hERG Blockers:  0.061 hERG Blockers (10um):  0.261
Human Hepatotoxicity (H-HT):  0.668 Drug-induced Liver Injury (DILI):  0.239
AMES Toxicity:  0.546 Rat Oral Acute Toxicity:  0.21
Maximum Recommended Daily Dose:  0.436 Skin Sensitization:  0.868
Carcinogencity:  0.323 Eye Corrosion:  0.013
Eye Irritation:  0.885 Respiratory Toxicity:  0.478
Drug-induced Neurotoxicity:  0.656 Ototoxicity:  0.414
Hematotoxicity:  0.266 Drug-induced Nephrotoxicity:  0.691
Genotoxicity:  0.973 RPMI-8226 Immunitoxicity:  0.096
A549 Cytotoxicity:  0.073 Hek293 Cytotoxicity:  0.306
BCF:   0.424
?
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:   2.984
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.064
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.406
?
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
NPO19266 Clausena excavata Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[11000023]
NPO23546 Clausena lansium Species Rutaceae Eukaryota leaves n.a. n.a. PMID[19327990]
NPO23546 Clausena lansium Species Rutaceae Eukaryota Stems n.a. n.a. PMID[22372931]
NPO23546 Clausena lansium Species Rutaceae Eukaryota Roots n.a. n.a. PMID[24798144]
NPO23546 Clausena lansium Species Rutaceae Eukaryota Leaves n.a. n.a. PMID[26523463]
NPO23546 Clausena lansium Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[30970599]
NPO23546 Clausena lansium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19266 Clausena excavata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19266 Clausena excavata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23546 Clausena lansium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19266 Clausena excavata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23546 Clausena lansium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19266 Clausena excavata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23546 Clausena lansium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23546 Clausena lansium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19266 Clausena excavata Species Rutaceae 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 NPC206681 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 NPC151706
1.0 High Similarity NPC476102
1.0 High Similarity NPC293377
1.0 High Similarity NPC49577
1.0 High Similarity NPC474811
1.0 High Similarity NPC90194
1.0 High Similarity NPC475318
1.0 High Similarity NPC474855
1.0 High Similarity NPC76785
1.0 High Similarity NPC273907
1.0 High Similarity NPC260045
1.0 High Similarity NPC9687
1.0 High Similarity NPC474787
1.0 High Similarity NPC118099
1.0 High Similarity NPC79465
0.5417 Remote Similarity NPC488662

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC206681 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