Pathways

Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a scaffolding protein that functions as a coregulator of several transcription factors and nuclear receptors. Notably, the PELP1 protein has a histone-binding domain, recognizes histone modifications and interacts with several chromatin-modifying complexes. PELP1 serves as a substrate of multitude of kinases, and phosphorylation regulates its functions in various complexes. Further, PELP1 plays essential roles in several pathways including hormonal signaling, cell cycle progression, ribosomal biogenesis, and the DNA damage response. PELP1 expression is upregulated in several cancers, its deregulation contributes to therapy resistance, and it is a prognostic biomarker for breast cancer survival. Recent evidence suggests that PELP1 represents a novel therapeutic target for many hormonal cancers.

Pemetrexed is an antifolate, it contains a pyrrolopyrimidine base within its structure that inhibits DNA synthesis and de novo biosynthesis of nucleotides. Once inside the cell via a folate transporter, it is converted to by folylpolyglutamate synthétase into its polyglutamate form. This new form is better retained in the cells and goes on to inhibit enzymes such as dihydrofolate reductase, thymidylate synthase and bifunctional purine biosynthesis protein (PURH). This drug is used to treat cancer specifically that of lung cancer or mesothelioma can be used in combination with pembrolizumab or cisplatin. It is not metabolized by much of the liver but excreted via the urine.

Metabolites of sildenafil are predicted with biotransformer.

Pemoline is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Pemoline passes through the liver and is then excreted from the body mainly through the kidney.

Penbutolol (also known as Levatol or Levatolol) is a beta blocker (non-selective) that are used for treat high blood pressure or chest pain. Penbutolol bind to beta1-adrenergic receptors in heart and vascular smooth muscle to block the binding of other adrenergic neurotransmitters such as norepinephrine, which lead to decreased blood pressure, heart rate and cardiac output. Penbutolol can also bind beta-2 adrenergic receptors in juxtaglomerular apparatus and bronchiole smooth muscle. In juxtaglomerular apparatus, penbutolol can prevent the production of aldosterone and angiotensin II by inhibiting renin production, which lead to prevention of water retention and vasoconstriction. In bronchiole smooth muscle, binding of penbutolol to beta-2 adrenergic receptors can also prevent vasoconstriction.

Penbutolol is a non-selective beta blocker. It can be administered orally, where it passes through hepatic portal circulation, and enters the bloodstream and travels to act on cardiomyocytes. In bronchial and vascular smooth muscle, penbutolol can compete with epinephrine for beta-2 adrenergic receptors. By competing with catecholamines for adrenergic receptors, it inhibits sympathetic stimulation of the heart. The reduction of neurotransmitters binding to beta receptor proteins in the heart inhibits adenylate cyclase type 1. Because adenylate cyclase type 1 typically activates cAMP synthesis, which in turn activates PKA production, which then activates SRC and nitric oxide synthase, its inhibition causes the inhibition of cAMP, PKA, SRC and nitric oxide synthase signaling. Following this chain of reactions, we see that the inhibition of nitric oxide synthase reduces nitric oxide production outside the cell which results in vasoconstriction. On a different end of this reaction chain, the inhibition of SRC in essence causes the activation of Caspase 3 and Caspase 9. This Caspase cascade leads to cell apoptosis. The net result of all these reactions is a decreased sympathetic effect on cardiac cells, causing the heart rate to slow and arterial blood pressure to lower; thus, penbutolol administration and binding reduces resting heart rate, cardiac output, afterload, blood pressure and orthostatic hypotension. By prolonging diastolic time, it can prevent re-infarction. One potentially less than desirable effect of non-selective beta blockers like penbutolol is the bronchoconstrictive effect exerted by antagonizing beta-2 adrenergic receptors in the lungs. Clinically, it is used to increase atrioventricular block to treat supraventricular dysrhythmias. Penbutolol also reduce sympathetic activity and is used to treat hypertension, angina, migraine headaches, and hypertrophic subaortic stenosis.