ROCK Targeted Library

Rho-associated protein kinases (ROCK) are serine/threonine kinases involved in numerous cellular motility regulatory processes from cell migration to cell contraction and control of the amount of microfilament. Depending on their subcellular localization, activation and other environmental factors, ROCK signaling can have different effects on cellular function. In addition, ROCKs play a key role in mediating the control of the action cytoskeleton by Rho family GTPases in response to extracellular signals. This signaling pathway contributes to diverse neuronal functions, providing a potential site for therapeutic interventions to promote neuronal regeneration and limit degeneration.

BOC Sciences has abilities in designing and synthesizing a ROCKs targeted library to deliver both ROCK1 and ROCK2 inhibitors.

Figure 1. ROCK structure and modes of regulation. (Svenja, H.; et al. 2015)

Library Design

1. Firstly, we have applied different ROCK1 and ROCK2 isoforms as targets for performing virtual screening. In addition, Gaussian software is available for the preparation of protein molecular conformations
2. Both ROCK kinase structures are optimized and validated using our well-designed protein preparation tools
3. ROCK1 and ROCK2 inhibitors with IC₅₀ lower than 1.5 μM are used to generate 3D conformers with different pH states
4. Then, a Glide operation is applied for all docking procedures, in which different H-bond constraints and hydrophobic regions will be carefully defined and applied during the docking process
5. Finally, the docked compounds from BOC Sciences compound collection are narrowed down according to the docking score values

Figure 2. ROCK targets. (Svenja, H.; et al. 2015)

ROCK Targeted Library Characteristics

• Favorable physicochemical parameters and solubility requirements
• No PAINS or toxic substances/unwanted functions: filtered by strict ‘Ro5-like’ physicochemical and most stringent in-house structural filters
• Bioactivity and safety confirmed by preclinical studies and clinical trials
• Structural diversity, medicinal activity, and cellular penetration
• Structural document, IC₅₀, and other chemical and biological data are provided
• All compounds are continually updated
• Compound cherry-picking service is provided

What We Deliver

• Delivered within 2 weeks in any customer-preferred format
• Powders, dry films or DMSO solutions formatted in vials, 96 or 384-well plates
• All compounds have a minimum purity of 90% assessed by ¹H NMR and HPLC
• Analytical data is provided

BOC Sciences provides professional, rapid and high-quality services of ROCK Targeted Library design at competitive prices for global customers. Personalized and customized services of ROCK Targeted Library design can satisfy any innovative scientific study demands. Our clients have direct access to our staff and prompt feedback to their inquiries. If you are interested in our services, please contact us immediately!