1. www.molecular-modeling.ch Background. For designing, discovering or developing a therapeutically relevant molecule, potency and selectivity to the target protein is only one side of the problem. Indeed absorption, distribution, metabolism, and excretion (ADME) must be optimized for the molecule to reach its tissue/target in sufficient amount. To reduce off-target and unwanted effects, predictive cheminformatics is recognized as a valid alternative to experimental procedures 1. Objectives. The SwissADME tool gives access through the web to a collection of models for predicting properties of small molecules and hence select the most promising to further study. step 1 (PD) step 2 (PK) step 3 (PD) PHYSICOCHEMICAL DATA Ponatinib has an low TPSA (moderate apparent polarity).  well absorbed by the GI- tract when taken orally.  prone to cross the Blood- Brain Barrier to enter the CNS. PHYSICOCHEMICAL DATA Ponatinib has an low TPSA (moderate apparent polarity).  well absorbed by the GI- tract when taken orally.  prone to cross the Blood- Brain Barrier to enter the CNS. OCTANOL/WATER PARTITION Ponatinib has a high log P (lipophilicity)  oxidation-prone by CYP450.  tendency to be extensively bound to plasma proteins.  Can block hERG-channel. OCTANOL/WATER PARTITION Ponatinib has a high log P (lipophilicity)  oxidation-prone by CYP450.  tendency to be extensively bound to plasma proteins.  Can block hERG-channel. WATER SOLUBILITY Ponatinib is poorly-to- moderately soluble  Potential problems for dose formulation.  Small amount excreted by kidney. WATER SOLUBILITY Ponatinib is poorly-to- moderately soluble  Potential problems for dose formulation.  Small amount excreted by kidney. PHARMACOKINETICS Ponatinib is predicted as:  substrate of P-glycoprotein (efflux from the brain).  Well absorbed by GI-tract (suited for oral administration). PHARMACOKINETICS Ponatinib is predicted as:  substrate of P-glycoprotein (efflux from the brain).  Well absorbed by GI-tract (suited for oral administration). DRUGLIKENESS Ponatinib is considered as a druglike molecule by multiple filters (only size and refractivity are slightly above thresholds).  Suited for oral administration. DRUGLIKENESS Ponatinib is considered as a druglike molecule by multiple filters (only size and refractivity are slightly above thresholds).  Suited for oral administration. CHEMICAL DESCRIPTION Ponatinib is a small molecule (!) CHEMICAL DESCRIPTION Ponatinib is a small molecule (!) MEDICINAL CHEMISTRY Ponatinib returned one alert (triple bound), which is a manageable problematic structural fragment. Ponatinib has a Synthetic Accessibility Score of 3.42 (on a scale from 1 [easy to make] to 10 [very difficult to make]).  Suited for medicinal chemistry and biological screening activities. MEDICINAL CHEMISTRY Ponatinib returned one alert (triple bound), which is a manageable problematic structural fragment. Ponatinib has a Synthetic Accessibility Score of 3.42 (on a scale from 1 [easy to make] to 10 [very difficult to make]).  Suited for medicinal chemistry and biological screening activities. SwissADME