Pathways

Pefloxacin is an antibiotic used to treat a variety of bacterial infections. Pefloxacin inhibits DNA gyrase (topoisomerase II) and topoisomerase IV. These proteins prevent supercoiling in bacterial DNA. The inhibition of DNA gyrase (topoisomerase II) and topoisomerase IV causes supercoiling of the bacterial DNA. This prevents DNA replication.

Pegaptanib serves as a selective vascular endothelial growth factor (VEGF) antagonist, employed to address neovascular (wet) age-related macular degeneration. This polynucleotide aptamer is designed to bind to VEGF, reducing both angiogenesis and vessel permeability, particularly for neovascular age-related macular degeneration cases. By targeting VEGF, which activates its receptors on vascular endothelial cells, pegaptanib mitigates processes like angiogenesis, increased vascular permeability, and inflammation that contribute to the progression of wet age-related macular degeneration, a significant cause of vision impairment. Pegaptanib's selectivity for VEGF165, a key isoform of VEGF-A responsible for pathological effects in wet AMD, inhibits its binding to receptors, thereby impeding the advancement of the condition without affecting the physiological isoform VEGF121. This treatment approach is especially effective for patients with conditions like wet AMD, where VEGF-A levels are elevated and contribute to disease progression.

Peginterferon alfa-2a is a modified form of recombinant human interferon, which is used to activate interferon alpha receptors in the JAK-STAT pathway. This is used to stimulate the innate antiviral response in the treatment of hepatitis B and C viruses. Peginterferon alfa-2a activate interferon alpha receptors 1 and 2 (IFNAR1 and IFNAR2) which are associated with tyrosine kinase 2 (TYK2) and JAK1 respectively. This receptor complex also phosphorylates STAT3 homodimers. The IFNAR complex phorphoylates STAT5 which binds with Crk-like protein (CRKL). This activates the transcription of gamma activated sequence (GAS) elements, which activates an inflammatory response and immunoregulation. The main pathway of IFNAR1 and IFNAR2 is through the phosphorylation of STAT1 and STAT2. Together with interferon regulatory factor (IRF9) they form the interferon-stimulated gene factor 3 (ISGF3). The ISGF3 translocates to the nucleus and initiates the trascription of Interferon-sensitive response element (ISRE). This leads to an antiviral response, immunoregulation, antigen presentation, and checkpoint proteins. THE ISRE genes also activate IFN regulated genes. These along with lipopolysaccharides or foreign pathogens activates interferon Regulatory Factor 7 (IRF7). IRF7 is phosphorylated and bound with nuclear factor kappa B (NFKB). This causes the induction of type 1 INFs, which further activates the pathway. IFNAR1 and IFNAR2 signal through TYK2 and JAK1 to also trigger the activation of the NFKB pathway through phosphorylated STAT3, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and TNF receptor-associated factors (TRAFs). They act through IKKa and IKKb to drive NFKB induction of genes associated with survival signals, antigen processing and presentation, and proliferation.

Peginterferon alfa-2b, also known as Pegintron or Sylatron, is a purified recombinant human interferon. It is used as part of combination therapy to treat chronic Hepatitis C caused by the Hepatitis C Virus (HCV). It is also used as an adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection. The mechanism of action is the inhibition of the viral replication in infected cells caused by the binding of the peginterferon to the human type 1 interferon receptors causing them to dimerize. This, in consequence, activates the JAK-STATS pathway which increases the expression of multiple genes involved in the innate antiviral response. Its immunomodulatory effects are the enhancement of the phagocytic activity, the activation of NK cells, the stimulation of cytotoxic T-lymphocytes, and the upregulation of the Th1 T-helper cell subset.

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.