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Pharmacophore and Virtual Screening of JAK3 inhibitors.

Rajeswari M, Santhi N, Bhuvaneswari V - Bioinformation (2014)

Bottom Line: The statistically significant pharmacophore hypothesis of AAHR.92 with r2 value of 0.942 was used as 3D query to search against 3D database namely Zincpharmer.A total of 2, 27,483 compounds obtained as hit were subjected to high throughput virtual screening (HTVS module of Schrodinger).Among the hits, ten compounds with good G-score ranging from -12.96 to -11.18 with good binding energy to JAK3 were identified.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Biotechnology and Bioinformatics, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore - 641 043, Tamil Nadu, India.

ABSTRACT
Janus kinase 3 (JAK3) is a non-receptor tyrosine kinases family of protein which is comprised of JAK1, JAK2, JAK3 and TYK2. It plays an important role in immune function and lymphoid development and it only resides in the hematopoietic system. Therefore, selective targeting JAK3 is a rational approach in developing new therapeutic molecule. In this study, about 116 JAK3 inhibitors were collected from the literature and were used to build four-point pharmacophore model using Phase (Schrodinger module). The statistically significant pharmacophore hypothesis of AAHR.92 with r2 value of 0.942 was used as 3D query to search against 3D database namely Zincpharmer. A total of 2, 27,483 compounds obtained as hit were subjected to high throughput virtual screening (HTVS module of Schrodinger). Among the hits, ten compounds with good G-score ranging from -12.96 to -11.18 with good binding energy to JAK3 were identified.

No MeSH data available.


Related in: MedlinePlus

Pharmacophoric features of active ligands
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Related In: Results  -  Collection


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Figure 3: Pharmacophoric features of active ligands

Mentions: The selected pharmacophore hypothesis included the followingfeatures (Figure 3): the hydrogen bond acceptor (sphere witharrow A2 and A3), hydrophobic group (H9 green sphere) andthe aromatic ring (R15 circle). The alignment generated by thebest pharmacophore model for active and inactive compound isshown in Figure 4. The key pharmacophore element of theAAHR.92 hypothesis: the aromatic ring (R15), which is mappedinto the benzene ring of benzimidazole or azobenzimidazole ofall active compounds, the hydrogen bond acceptor (A2 and A3)features are in N of prymidine, N and O of Purinone and O ofthe chroman ring and the hydrophobic groups are featured onalkyl substituent.


Pharmacophore and Virtual Screening of JAK3 inhibitors.

Rajeswari M, Santhi N, Bhuvaneswari V - Bioinformation (2014)

Pharmacophoric features of active ligands
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3974243&req=5

Figure 3: Pharmacophoric features of active ligands
Mentions: The selected pharmacophore hypothesis included the followingfeatures (Figure 3): the hydrogen bond acceptor (sphere witharrow A2 and A3), hydrophobic group (H9 green sphere) andthe aromatic ring (R15 circle). The alignment generated by thebest pharmacophore model for active and inactive compound isshown in Figure 4. The key pharmacophore element of theAAHR.92 hypothesis: the aromatic ring (R15), which is mappedinto the benzene ring of benzimidazole or azobenzimidazole ofall active compounds, the hydrogen bond acceptor (A2 and A3)features are in N of prymidine, N and O of Purinone and O ofthe chroman ring and the hydrophobic groups are featured onalkyl substituent.

Bottom Line: The statistically significant pharmacophore hypothesis of AAHR.92 with r2 value of 0.942 was used as 3D query to search against 3D database namely Zincpharmer.A total of 2, 27,483 compounds obtained as hit were subjected to high throughput virtual screening (HTVS module of Schrodinger).Among the hits, ten compounds with good G-score ranging from -12.96 to -11.18 with good binding energy to JAK3 were identified.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Biotechnology and Bioinformatics, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore - 641 043, Tamil Nadu, India.

ABSTRACT
Janus kinase 3 (JAK3) is a non-receptor tyrosine kinases family of protein which is comprised of JAK1, JAK2, JAK3 and TYK2. It plays an important role in immune function and lymphoid development and it only resides in the hematopoietic system. Therefore, selective targeting JAK3 is a rational approach in developing new therapeutic molecule. In this study, about 116 JAK3 inhibitors were collected from the literature and were used to build four-point pharmacophore model using Phase (Schrodinger module). The statistically significant pharmacophore hypothesis of AAHR.92 with r2 value of 0.942 was used as 3D query to search against 3D database namely Zincpharmer. A total of 2, 27,483 compounds obtained as hit were subjected to high throughput virtual screening (HTVS module of Schrodinger). Among the hits, ten compounds with good G-score ranging from -12.96 to -11.18 with good binding energy to JAK3 were identified.

No MeSH data available.


Related in: MedlinePlus