Browsing Pathways

Gefitinib is an anti-EGFR drug used in the treatment of some cancers. EGFR is linked multiple signalling pathways involved in tumour growth and angiogenesis such as the Ras/Raf pathway and the PI3K/Akt pathways. These pathways ultimately lead to the activation of transcription factors such as Jun, Fos, and Myc, as well as cyclin D1, which stimulates cell growth and mitosis. Uncontrolled cell growth and mitosis leads to cancer. Gefitinib acts as an anticancer drug by binding to the intracellular tyrosine kinase domain of the EGFR and blocking its activity. This in turn inhibits downstream signalling and prevents tumour growth.

Nalbuphine (also known as Rubuphine and Nubain) is a competitive antagonist of mu-type and kappa-type opioid receptor in the central nervous system (CNS). Nalbuphine is also a type of medication that are mainly used for treat pain. Binding of nalbuphine can prevent the effects that caused by endogenous opioids, which results in antagonization of effects of opiates such as respiratory depression or drug craving.

Pentazocine (also known as Talwin) is a type of medication that can relieve moderate to severe pain. Pentazocine can bind to mu-type opioid receptor and kappa-type opioid receptor on neuron of central nerves system (CNS). Binding of pentazocine on mu-type opioid receptor and kappa-type opioid receptor can lead to decreased level of neuronal excitability and hyperpolarization. After binding to the receptor, pentazocine will slowly dissociate.

Methadyl Acetate (also known as Acetylmethadol) is analgesic that can bind to mu-type opioid receptor to activate associated G-protein in the sensory neurons of central nervous system (CNS), which will reduce the level of intracellular cAMP by inhibiting adenylate cyclase. The binding of methadyl acetate will eventually lead to reduced pain because of decreased nerve conduction and release of neurotransmitter. Hyperpolarization of neuron is caused by inactivation of calcium channels and activation of potassium channels via facilitated by G-protein.

Clomocycline is a tetracycline antibiotic that inhibits bacterial cell growth by inhibiting translation. Clomocycline is lipophilic and easily diffuses across cell membranes or enters cells via porin channels in the bacterial membrane. It binds to the 30S ribosomal subunit and prevents the aminoacyl tRNA from binding to the A site of the ribosome-RNA complex. Clomocycline binding is reversible in nature. Clomocycline may be used to treat acne, gum disease, and other bacterial infections such as chalmydia, brucellosis, bartonellosis and cholera. Clomocycline is also effective against certain strains of malaria and may also be prescribed for the treatment of Lyme disease.

Dipyridamole (also known as Persantine) can bind and inhibit cAMP-specific 3',5'-cyclic phosphodiesterase 4D at platelet cell, which prevent the release of arachidonic acid form membrane phospholipids that eventually decreasing thromboxane A2 activity. Dipyridamole can also induce adenylate cyclase activity by releasing prostacyclin, which lead to inhibition of platelet aggregation and increased intraplatelet concentration of cAMP.

Olmesartan (also named Benicar or Olmetec) is an active metabolite of angiotensin II receptor blockers (ARBs) pro drug, olmesartan medoxomil. Olmesartan medoxomi converts to olmesartan rapidly in gastrointestinal tract during absorption. Olmesartan competes with angiotensin II to bind type-1 angiotensin II receptor (AT1) in many tissues (e.g. vascular smooth muscle, the adrenal glands, etc.) to prevent increasing sodium, water reabsorption and peripheral resistance (that will lead to increasing blood pressure) via aldosterone secretion that is caused by angiotensin II. Therefore, action of olmesartan binding to AT1 will result in decreasing blood pressure. For more information on the effects of aldosterone on electrolyte and water excretion, refer to the description of the \spironolactone\:http://pathman.smpdb.ca/pathways/SMP00134/pathway or \triamterene\:http://pathman.smpdb.ca/pathways/SMP00132/pathway pathway, which describes the mechanism of direct aldosterone antagonists. Olmesartan is an effective agent for reducing blood pressure and may be used to treat essential hypertension and heart failure.

Benazepril, brand name Lotensin, belongs to the class of drugs known as angiotensin-converting enzyme (ACE) inhibitors and is used primarily to lower high blood pressure (hypertension). This drug can also be used in the treatment of congestive heart failure and type II diabetes. Benazepril is a prodrug which, following oral administration, undergoes biotransformation in vivo into its active form benazeprilat via cleavage of its ester group by the liver. Angiotensin-converting enzyme (ACE) is a component of the body's renin–angiotensin–aldosterone system (RAAS) and cleaves inactive angiotensin I into the active vasoconstrictor angiotensin II. ACE (or kininase II) also degrades the potent vasodilator bradykinin. Consequently, ACE inhibitors decrease angiotensin II concentrations and increase bradykinin concentrations resulting in blood vessel dilation and thereby lowering blood pressure.

Docetaxel, a semisynthetic analogue of paclitaxel, is an anticancer agent classified as a microtubule-stabilizing agent. Similar to paclitaxel, it exerts cell killing effects by disrupting mitosis in dividing cells. Microtubules are made up of α- and β- tubulin heterodimers arranged head to tail and assembled to form a cylinder. Microtubules possess complex polymerization dynamics that are essential for movement of chromosomes and proper segregation of daughter cells during mitosis. Docetaxel binds directly to the inner surface of β-subunits along the length of microtubules. Binding is thought to induce a conformational change in tubulin that increases its affinity for neighbouring molecules. At sufficiently high concentrations, docetaxel can bind to β-tubulin in a one to one ratio and stimulate microtubule polymerization. At lower clinically relevant drug concentrations, docetaxel stabilizes microtubules and prohibits further polymerization and depolymerization. Suppression of microtubule dynamics may prevent chromosomes from moving from the spindle poles to the metaphase plate slowing or preventing progression from metaphase to anaphase. Cells enter a state of mitotic arrest from which they may progress to one of several fates. The tetraploid cell may undergo unequal cell division producing aneuploid daughter cells. Alternatively, it may exit the cell cycle without undergoing cell division, a process termed mitotic slippage or adaptation. These cells may continue progressing through the cell cycle as tetraploid cells (Adaptation I), may exit G1 phase and undergo apoptosis or senescence (Adaption II), or may escape to G1 and undergo apoptosis during interphase (Adaptation III). Another possibility is cell death during mitotic arrest. Alternatively, mitotic catastrophe may occur causing cell death. Docetaxel is susceptible to cellular drug resistance caused by drug efflux via a number of multidrug resistance-associated proteins.

Proparacaine exerts its local anaesthetic effect by blocking voltage-gated sodium channels in peripheral neurons. Proparacaine diffuses across the neuronal plasma membrane in its uncharged base form. Once inside the cytoplasm, it is protonated and this protonated form enters and blocks the pore of the voltage-gated sodium channel from the cytoplasmic side. For this to happen, the sodium channel must first become active so that so that gating mechanism is in the open state. Therefore proparacaine preferentially inhibits neurons that are actively firing.