Screening Libraries | Natural Product-like Compounds
Natural Product-like Compounds
Remarkable structural diversity and drug-likeness of molecular scaffolds identified in natural compounds provides a basis for the design of novel natural product-derived compound libraries for drug discovery1,2.
Life Chemicals presents a collection of Natural Product-like compounds, containing 2 subsets generated through following approaches:
● Similarity based search against commercial databases of Timetek, Specnet, Analyticon, Selleck. 1,000 compounds in stock.
● Superposition of chemoinformatics and substructure search methods applied to entire stock with selection of overlapping items1,3. 2,400 compounds in stock.
Natural Products-like Compounds Library - Similarity Search
The Library was designed using 2D fingerprint similarity filtering of Life Chemicals's stock collection using commercial databases of Timetek, Specnet, Analyticon, Selleck as the reference sets. A Tanimoto 85% similarity cut-off was applied to afford about 1,000 stock available compounds.
Natural Products-like Compounds Library - Chemoinformatics & Substructure Search
Overlapping both collections obtained after analysis of Life Chemicals' stock by two different methods - chemical descriptors calculation (7,300 compounds) and natural-likeness scoring (9,700 compounds) a chemical space for about 2,400 compounds with good values in both studies was obtained.
Descriptor-based Selection Method:
1. Substructure search for natural-like scaffolds in Life Chemicals Stock. ~62K were selected from about 380K of compounds.
2. Validation of method and clarification of details from publication with calculation of said parameters (Tab.1) for Drugs (COBRA), Pure Natural Products (PNP, MNP), NPs and Derivatives/Analogs (SNP), and NP-Based Combinatorial Compounds (NatDiv).
|Molecular mass||414.5 (142.7)||393.9 (196.3)||503.6 (250.1)||409.2 (102.4)||441.3 (74.2)|
|# heavy atoms||29.1||28.2||34.6||29.1||31.1|
|SlogP||3.5 (2.2)||2.3 (2.7)||3.9 (2.6)||3.7 (1.7)||2.1 (1.8)|
|# nitrogen atoms||3.0||0.7||1.2||2.1||3.6|
|# oxygen atoms||3.4||5.9||6.1||4.3||4.4|
|LipViol ≤ 2||10%||18%||30%||10%||8%|
|TPSA||90.5 (55.4)||98.9 (82.1)||108.9 (88.4)||83.2 (35.1)||104.7 (35.9)|
|# aromatic atoms||12.4||5.1||3.5||11.8||9.5|
|# chiral atoms||1.4||5.5||6.3||1.4||3.3|
Scaffold diversity of natural products: inspiration for combinatorial library design. Kristina Grabowski, Karl-Heinz Baringhausb and Gisbert Schneider
Natural products-likeness Calculator:
Fig.1. Standard cross-platform view of Taverna 2.0 with a schema of connections between template files, natural-product likeness calculator and query file - SDF of our stock
Fig. 2. Natural product-likeness scorer. Distribution of real natural products.
1. Properties and Architecture of Drugs and Natural Products Revisited. Kristina Grabowski and Gisbert Schneider.
2. Matthew E Welsch, Scott A Snyder and Brent R Stockwell Current Opinion in Chemical Biology 2010, 141 - 145
3. Natural Product-likeness Score and its Application for Prioritization of Compound Libraries. Peter Ertl, Silvio Roggo, and Ansgar Schuffenhauer. J. Chem. Inf. Model. 2008, 48, 68-74
4. Scaffold diversity of natural products: inspiration for combinatorial library design. Kristina Grabowski, Karl-Heinz Baringhausb and Gisbert Schneider.