Modulatori enzimatici

<p>Inhibitor of BCR-ABL1 kinase</p>

<p>Teniposide is a cytotoxic drug that is used in the treatment of refractory childhood acute lymphoblastic leukemia. It has antitumour activity. It is a type II topoisomerase inhibitor. This drug inhibits DNA synthesis by forming a complex with topoisomerase II and DNA.</p>

Brain-penetrant inhibitor of anaplastic lymphoma kinase (ALK) and proto-oncogene kinase ROS1. It is a reversible ATP-competitor, interacting with P-loop (L1122, G1123, V1130) and K1150 residue of ALK tyrosine kinase. It has major implications in the treatment of non-small cell lung cancer (NSCLC). The compound is used for resensitization of drug resistant, ALK-mutated cancers to crizotinib chemotherapy and was shown to trigger the regression of EML40ALK-driven brain metastases.

<p>Inhibitor of ALK1, ALK2, ALK3 and ALK6 kinases and bone morphogenetic protein (BMP) pathway. LDN 1931189 is a dorsomorphin derivative that inhibits BMP-mediated activation of Smad, Akt and p38 signalling. LDN 193189 promotes differentiation of human pluripotent cells into PAX6+ anterior neural ectoderm. In combination with basic fibroblast growth factor (FGF2), LDN 193189 promotes differentiation of mouse pluripotent stem cells into inner ear sensory epithelium.</p>

<p>Enalapril is a long-acting angiotensin-converting enzyme inhibitor. It is used to treat hypertension and congestive heart failure, as well as chronic cough due to postnasal drip or bronchitis. Enalapril is an active inhibitor of the synthesis of angiotensin II and other vasoconstrictor substances that are involved in the regulation of blood pressure. It binds reversibly to the active site on angiotensin-converting enzyme (ACE) and blocks its activity by forming strong hydrogen bonds with residues on ACE, thereby preventing it from converting angiotensin I into angiotensin II. This leads to a significant reduction in blood pressure.</p>

Inhibits MET, VEGFR1, VEGFR2; VEGFR3 receptor tyrosine kinases; antineoplastic

<p>Dasatinib is a potent inhibitor of tyrosine kinases and is used in the treatment of chronic myelogenous leukemia, gastrointestinal stromal tumors, and other types of cancer. It also inhibits many SRC- family kinases. Dasatinib has been shown to inhibit the proliferation of cancer cells, leading to cell lysis. Additionally, it has anti-angiogenic effects in vivo, inhibiting the development of new blood vessels in solid tumours.</p>

<p>Inhibitor of PDE4 enzyme</p>

<p>Inhibitor of β-lactamase enzymes</p>

<p>Fasudil hydrochloride is a Rho-kinase inhibitor, which is a synthetic compound derived from natural sources, primarily used in scientific research. The mode of action of Fasudil hydrochloride involves the inhibition of Rho-associated protein kinase (ROCK), a crucial player in the regulation of the actin cytoskeleton. By inhibiting ROCK, Fasudil alters various cellular functions, including contraction, motility, proliferation, and apoptosis.</p>

Nicotinamide is a form of vitamin B that is found in food and it used to treat many conditions such as pellagra and acne. It replenishes cellular energy and has anti-inflammatory effects. Nicotinamide is an inhibitor of the enzyme SIRT1 in vitro but can be a stimulator in cells.

4-Methylpyrazole is a competitive inhibitor of alcohol dehydrogenase, which can be used to treat methanol and ethylene glycol poisoning. It is also used to inhibit the metabolism of ethanol by blocking the conversion of ethanol to acetaldehyde. 4-Methylpyrazole is metabolized into 4-methylpyridinium ion (4MP) by alcohol dehydrogenase, which prevents the conversion of acetaldehyde to acetic acid. This results in an increase in blood levels of acetaldehyde and a decrease in blood levels of acetic acid, leading to an accumulation of toxic metabolites such as formic acid. In addition, 4-methylpyrazole inhibits the enzyme glycol dehydrogenase that breaks down glycols into their harmless components. This leads to an accumulation of toxic intermediate products that are converted back into glycols.

<p>Inhibitor of ErbB2 (IC50 = 3 nM) and EGFR kinase (IC50 = 6.4 nM) with anti-proliferative effects. It inhibits ErbB2 receptor autophosphorylation and induces G1 cell cycle block. The CP 724714 treatment induces reduction of downstream ErbB2 receptor tyrosine kinase signalling, tumor cell apoptosis, release of caspase 3 and regression of tumors in in vivo and in vitro models.</p>

<p>Rensocatib is a reversible inhibitor of DPP-1, also known as cathepsin C, which is a peptidase involved in the activation of neutrophil, an elastase-like serine protease in lung tissue. Brensocatib is an oral drug used to treat infections of the airways (lungs) that are characterised by a permanent enlargement and presenting symptoms such as, coughing and greater mucus production (bronchiectasis). Alternative names of brensocatib are INS-1007 and AZD7986.</p>

<p>Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) used to reduce inflammation, relieve pain and reduce fever. The mechanism of action of ibuprofen has not been fully elucidated, but it may be due to inhibiting the enzyme cyclooxygenase and thus decreasing the synthesis of prostaglandins allowing a reduction of pain and inflammation.</p>

<p>Inhibitor of S-adenosylhomocysteine hydrolase that disrupts histone methylation by EZH2. Anti-proliferative in some breast cancer and invasive prostate cancer cell lines. One of four key molecules required for inducing chemical reprogramming of somatic cells into induced pluripotent stem cells (iPSC).</p>

<p>Inhibitor of fibroblast growth factor receptors (FGFR1, FGFR2 and FGFR3). Demonstrated anti-tumor effects in pre-clinical models of FGFR-driven tumors. AZD 4547 resulted in tumor progression when applied on a patient-derived model of FGFR1-amplified squamous cell lung disease. Antineoplastic effects also observed in FGFR2-amplified gastric cancer.</p>

<p>Moclobemide is a monoamine oxidase inhibitor that is used to treat major depressive disorder and dipolar disorder. This drug’s mechanism of action involves the reversible inhibition of the enzyme MAO-A. The inhibition of this enzyme results in a decreased metabolism and destruction of neurotransmitters thus relieving the symptoms of depression and bipolar disorder.</p>

Orally available prodrug of gemcitabine

<p>Inhibitor of dopamine-?-hydroxylase</p>