The emergence and evolution of new immunological cancer therapies has sparked a rapidly growing interest in discovering novel pathways to treat cancer. Toward this aim, a novel series of pyrrolidine derivatives (compound ) were identified as potent inhibitors of ERK1/2 with excellent kinase selectivity and dual mechanism of action but suffered from poor pharmacokinetics (PK). The challenge of PK was overcome by the discovery of a novel 3()-thiomethyl pyrrolidine analog . Lead optimization through focused structure-activity relationship led to the discovery of a clinical candidate suitable for twice daily oral dosing as a potential new cancer therapeutic.

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Objective: To develop precise, accurate and reproducible stability assay method by RP-HPLC for estimation of dapagliflozin in API and pharmaceutical dosage form. Methods:The adequate separation was carried using agilent C18 (4.6 ml (millimeter)*150,5 µm (micromiter), mixture of acetonitrile: di-potassium hydrogen phosphate with pH-6.5 adjusted with OPA (40:60 %v/v) as a mobile phase with the flow rate of 1 ml/min (milliliter/minute) and the effluent was monitored at 222 nm (nanometer) using photo diode array detector. The retention time of dapagliflozin API and dapagliflozin tablet were 3.160 min (minute) and 3.067 min (minute) respectively.Results: Linearity for dapagliflozin was found in the range of 50-150µg/ml (microgram/milliliter) (R 2 = 0.99) respectively. The accuracy of the present method was evaluated at 50 %, 100% and 150%. The % recoveries of dapagliflozin API and tablet were found to be in the range of 99.00-99.99 % and 98.50-99.99 % respectively. Precision studies were carried out and the relative standard deviation values were less than two. The method was found to be robust. Conclusion:The proposed method was found to be specific, accurate, precise and robust can be used for estimation of dapagliflozin in API and Pharmaceutical dosage form.

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A new simple, precise, accurate, specific and selective high performance thin layer chromatographic (HPTLC) method has been developed for the simultaneous estimation of Terbinafine hydrochloride (TH) and Mometasone furoate (MF) in cream dosage form. The chromatographic separation was achieved on Merck precoated silica gel aluminium plate 60 F254 using Toluene: Ethyl acetate: Glacial acetic acid (8: 4: 0.1 v/v) as mobile phase. The densitometric scanning was carried out at 248 nm. Response was found to be linear in the concentration range of 1000-3000 ng/band with correlation coefficient (r 2 = 0.999) for Terbinafine hydrochloride and 100-300 ng/band with correlation coefficient (r 2 = 0.998) for Mometasone furoate. All parameters of method, repeatability, precision, LOD, LOQ, % recovery were validated as per ICH guidelines. The proposed procedure was successfully applied for the simultaneous determination of both drugs in commercial cream preparation. The advantage of the method is simplicity, reasonable sensitivity, rapidity, excellent resolving power, low cost and is a more effective option than other chromatographic techniques in routine quality control.