Discovery and development of direct thrombin inhibitors information
Direct thrombin inhibitors (DTIs) are a class of anticoagulant drugs that can be used to prevent and treat embolisms and blood clots caused by various diseases. They inhibit thrombin, a serine protease which affects the coagulation cascade in many ways. DTIs have undergone rapid development since the 90's. With technological advances in genetic engineering the production of recombinant hirudin was made possible which opened the door to this new group of drugs. Before the use of DTIs the therapy and prophylaxis for anticoagulation had stayed the same for over 50 years with the use of heparin derivatives and warfarin which have some well known disadvantages. DTIs are still under development, but the research focus has shifted towards factor Xa inhibitors, or even dual thrombin and fXa inhibitors that have a broader mechanism of action by both inhibiting factor IIa (thrombin) and Xa. A recent review of patents and literature on thrombin inhibitors has demonstrated that the development of allosteric and multi-mechanism inhibitors might lead the way to a safer anticoagulant.[1]
^Mehta, AY; Jin, Y; Desai, UR (Jan 2014). "An update on recent patents on thrombin inhibitors (2010 - 2013)". Expert Opinion on Therapeutic Patents. 24 (1): 47–67. doi:10.1517/13543776.2014.845169. PMID 24099091. S2CID 24817396.
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Directthrombininhibitors (DTIs) are a class of anticoagulant drugs that can be used to prevent and treat embolisms and blood clots caused by various...
Directthrombininhibitors (DTIs) are a class of medication that act as anticoagulants (delaying blood clotting) by directly inhibiting the enzyme thrombin...
drugs from the class ofdirect Xa inhibitors are marketed worldwide. Rivaroxaban (Xarelto) was the first approved FXa inhibitor to become commercially...
Several other directthrombininhibitors are derived chemically from hirudin. Hirudotherapy Discoveryanddevelopmentofdirectthrombininhibitors PDB: 4HTC...
antithrombin to thrombin (as well as factor Xa). The directthrombininhibitors, a newer class of medication, directly inhibitthrombin by binding to its...
heparin and related compounds increase the action of antithrombin on thrombinand factor Xa. A newer class of drugs, the directthrombininhibitors, is under...
free form. These direct factor Xa inhibitors can be administered orally, as can dabigatran etexilate, which is a directthrombininhibitor. Fondaparinux...
Argentina and Brazil). Ximelagatran, a directthrombininhibitor, was the first member of this class that can be taken orally. It acts solely by inhibiting the...
Xa activity rather than inhibitingthrombin activity, with the aim of facilitating a more subtle regulation of coagulation and an improved therapeutic...
coagulation cascade, inhibiting both thrombin formation anddevelopmentof thrombi. Rivaroxaban does not inhibitthrombin (activated Factor II), and no effects...
EH, Toole JJ (February 1992). "Selection of single-stranded DNA molecules that bind andinhibit human thrombin". Nature. 355 (6360): 564–566. Bibcode:1992Natur...
coagulation, in particular purification of prothrombin andthrombin" "Parkinsons disease and its treatment by extirpation of the premotor cortex" "Typhus fever...
pathway during a first wave of aggregation, leading to thrombin generation and PAR‐1 activation, which evokes a second wave of aggregation. Platelet activation...
atrox and Bothrops moojeni, venomous species of pit viper found east of the Andes in South America. It cleaves fibrinogen, similarly to thrombin. Batroxobin...
of a light chain and a heavy chain connected by a disulfide bond.: 4673 The protein C zymogen is activated when it binds to thrombin, another protein...
including acute ischemic stroke and catheter occlusion. NU172, a directthrombininhibitor in Phase I development for use as a short-acting anticoagulant...
Darexaban (YM150) is a directinhibitorof factor Xa created by Astellas Pharma. It is an experimental drug that acts as an anticoagulant and antithrombotic to...
2020). "Discoveryof novel phosphatidylcholine-specific phospholipase C drug-like inhibitors as potential anticancer agents". European Journal of Medicinal...
the direct result of advancements made in proteomic-centered methods and the indirect result of more widely available and cost-effective forms of transcriptomics...
Akassoglou and her team tracked the activity patterns ofthrombinand found that thrombin activity in the CNS preceded any sign of disease, and when thrombin activity...
aggregation, degranulation, and blood clot-promoting responsiveness to a wide array of physiological (e.g. thrombin) and pathological (e.g. atheromatous...
sub-discipline of biology encompassing all the genomic and proteomic approaches devoted to the study of proteases, their inhibitors, and their substrates...
"Discoveryof potent SOS1 inhibitors that block RAS activation via disruption of the RAS-SOS1 interaction". Proceedings of the National Academy of Sciences...
expressed on activated endothelial cells and platelets. Synthesis of P-selectin can be induced by thrombin, leukotriene B4, complement fragment C5a,...
matrix metalloproteinase, thrombin, cathepsin, and elastase. Thrombospondin-1 binds to the reelin receptors, ApoER2 and VLDLR, thereby affecting neuronal...
(toxins or small molecule inhibitors). Such "assays" are commonly used in drug discoverydevelopment by pharmaceutical and biotechnology companies. Most...
acute vascular rejection, and include administering a synthetic thrombininhibitor to modulate thrombogenesis, depletion of anti-galactose antibodies...
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