Natural Product: NPC208067

Natural Product IDNPC208067
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ATKYNAZQGVYHIB-XGUBFFRZSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0000492] Tropane alkaloids

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 ATKYNAZQGVYHIB-XGUBFFRZSA-N
Standard InCHI InChI=1S/C16H21NO3/c18-10-15(11-4-2-1-3-5-11)16(19)20-14-8-12-6-7-13(9-14)17-12/h1-5,12-15,17-18H,6-10H2/t12-,13+,14-,15-/m0/s1
SMILES c1ccc(cc1)[C@H](CO)C(=O)O[C@H]1C[C@@H]2CC[C@H](C1)N2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   275.15 Volume:   286.444
?
Van der Waals volume.
Dense:   0.961 LogP:   1.384
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.099
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.467
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   16.0
TPSA:   58.56
?
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:   0.819 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.26 Fsp3:   0.562
MCE-18:   53.4
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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:   0.177 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.066
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.052
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.011 Promiscuous compounds:   0.454

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.204 MDCK Permeability:   -5.127
Pgp-inhibitor:   0.082 Pgp-substrate:   0.999
PAMPA:   0.854
?
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%):   0.013 30% Bioavailability (F30%):   0.85
50% Bioavailability (F50%):   0.918

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.471
Plasma Protein Binding (PPB):   31.636% Volume Distribution (VD):   0.313
Fu: 63.119%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.025
OATP1B3 inhibitor:   0.006 BCRP inhibitor:   0.169
BSEP inhibitor:   0.195

ADMET: Metabolism

CYP1A2-inhibitor:   0.006 CYP1A2-substrate:   0.009
CYP2C19-inhibitor:   0.057 CYP2C19-substrate:   0.016
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.004
CYP3A4-inhibitor:   0.922 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.46
HLM stability:   0.051
?
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):  7.544 Half-life (T1/2):  1.195

ADMET: Toxicity

hERG Blockers:  0.121 hERG Blockers (10um):  0.287
Human Hepatotoxicity (H-HT):  0.779 Drug-induced Liver Injury (DILI):  0.121
AMES Toxicity:  0.528 Rat Oral Acute Toxicity:  0.356
Maximum Recommended Daily Dose:  0.837 Skin Sensitization:  0.969
Carcinogencity:  0.245 Eye Corrosion:  0.037
Eye Irritation:  0.695 Respiratory Toxicity:  0.596
Drug-induced Neurotoxicity:  0.756 Ototoxicity:  0.466
Hematotoxicity:  0.244 Drug-induced Nephrotoxicity:  0.798
Genotoxicity:  0.563 RPMI-8226 Immunitoxicity:  0.054
A549 Cytotoxicity:  0.077 Hek293 Cytotoxicity:  0.19
BCF:   0.199
?
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:   2.856
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.07
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.311
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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
NPO14552 Stevia tomentosa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9779 Streptomyces endus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO9779 Streptomyces endus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO16843 Euonymus revolutus Species Celastraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14552 Stevia tomentosa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8689 Datura suaveolens Species Solanaceae 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 NPC208067 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
0.5577 Remote Similarity NPC602249
0.5472 Remote Similarity NPC213126
0.5472 Remote Similarity NPC84281
0.5472 Remote Similarity NPC169485
0.5472 Remote Similarity NPC317474
0.5472 Remote Similarity NPC209773
0.5472 Remote Similarity NPC609072
0.5306 Remote Similarity NPC602040
0.5273 Remote Similarity NPC245836
0.5273 Remote Similarity NPC233910
0.5273 Remote Similarity NPC39830

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC208067 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
0.5472 Remote Similarity NPD2610 Approved
0.5472 Remote Similarity NPD2611 Phase 4
0.5472 Remote Similarity NPD2612 Phase 4
0.537 Remote Similarity NPD3132 Phase 4
0.5273 Remote Similarity NPD2570 Phase 4
0.5273 Remote Similarity NPD2571 Approved
0.5273 Remote Similarity NPD2572 Clinical (unspecified phase)
0.5273 Remote Similarity NPD2573 Approved
0.5273 Remote Similarity NPD2574 Discontinued
0.5179 Remote Similarity NPD2566 Approved
0.5179 Remote Similarity NPD3089 Approved
0.5179 Remote Similarity NPD3090 Approved
0.5179 Remote Similarity NPD4217 Approved
0.5179 Remote Similarity NPD4218 Phase 4
0.5088 Remote Similarity NPD3087 Approved
0.5088 Remote Similarity NPD3088 Approved
0.5088 Remote Similarity NPD3131 Approved
0.5088 Remote Similarity NPD4215 Approved
0.5088 Remote Similarity NPD4216 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