title: Quantifying the structural requirements for designing newer FLT3 inhibitors.
abstract: RTKs - Receptor Tyrosine Kinases are the key regulators for cellular function and any abnormalities in the signaling of such leads to cancer. Mutations that result in the constitutive activation of this receptor result in Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia. Pharmacophore mapping, a well-established method is used to build up 3D QSAR model from two classes of compounds viz. 2-acylaminothiophene-3-carboxamide derivatives and 4-amino-6-piperazin-1yl-pyrimidine-5-carbaldehyde oxime derivatives, which helps us to quantify the crucial structural requirements for designing newer potent inhibitors for FLT3. The derived model AADHR.939 (Pearson- R = 0.8912, q(2) = 0.7471 and non-cross-validated r(2) = 0.9154) shows that the ring feature is quite crucial for the FLT3 inhibitory activity. Moreover the model is showing 94% predicted activity, which makes an understanding that the model is capable of finding newer potent molecules from any database.
authors: Biomedical Informatics Centre, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna-800007, Bihar, India.
authors: Rajiv Kumar
authors: RK
authors: Kar
authors: Priyanka
authors: P
authors: Suryadevara
authors: Rajesh
authors: R
authors: Roushan
authors: Ganesh Chandra
authors: GC
authors: Sahoo
authors: Manas Ranjan
authors: MR
authors: Dikhit
authors: Pradeep
authors: P
authors: Das
mesh_terms: D000577:Amides / Q000737:chemistry; D003198:Computer Simulation; D015195:Drug Design; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D010091:Oximes / Q000737:chemistry; D010879:Piperazines / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D011743:Pyrimidines / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D012107:Research Design; D055672:Static Electricity; D013816:Thermodynamics; D013876:Thiophenes / Q000737:chemistry; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors* / Q000737:chemistry*
chemical_list: D000577:Amides; D010091:Oximes; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013876:Thiophenes; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3