Therapeutic target

Though dental afflictions constitute a very significant disease entity, these have received relatively little attention from medicinal chemists. (The fluoride toothpastes may form an important exception.) This therapeutic target Is, however, sufficiently Important to be the focus of at least some research. A highly functionalized piperazine derivative that has come out of such work shows prophylactic activity against dental caries. Condensation of the enol ether 1 of thiourea with ji-pentylisocyanate gives the addition product 1J. Reaction of this with diamine 78, derived from piperazine, leads to substitution of the methylthio moiety by the primary amine, in all likelihood by an addition-elimination sequence. There is thus obtained ipexidine (79). ... 

Table 9.2b). Increasing also is the list of phenotypes associated with these dimerization processes. With the emergence of receptor dimers as possible therapeutic targets have come parallel ideas with dimerized ligands (see Section 9.5). 

Jacobson KA, Gao ZG (2006) Adenosine receptors as therapeutic targets. Nat Rev Drug Discov 5 247-264... 

Brown J, Plutzky J (2007) PPARs as transcriptional nodal points and therapeutic targets. Circulation 115 518-533... 

Calpain-10 (CAPN10) is the fust diabetes gene to have been identified through a genome scan. The discovery of calpain-10 has identified it as a molecule of importance to insulin signaling and secretion that may have relevance to the fiiture development of novel therapeutic targets for the treatment of type 2 diabetes. 

Hall JM, McDonnell DP (2005) Coregulators in nuclear estrogen receptor action. From concept to therapeutic targeting. Mol Interv 5 343-57. 

Holmes A, Picciotto MR (2006) Galanin a novel therapeutic target for depression, anxiety disorders and drag addiction CNS Neurol Disord Drag Targets 5 225-232... 

Nature has created a diverse array of plant and animal toxins that act at mammalian muscle and ganglionic nAChRs or invertebrate nAChRs because the critical physiological functions of these receptors make them prime targets for defensive or predatory strategies. More recently, the perceived validity of neuronal nAChR as therapeutic targets has prompted the generation of new synthetic ligands. Examples are listed in Table 1. 

CA C1 C01.070 Dipeptidyl-peptidase I Potential therapeutic target for treatment of sepsis... 

Turini ME, DuBois RN (2002) Cyclooxygenase-2 a therapeutic target. Annu Rev Med 53 35-57... 

Teicher BA (2006) Protein kinase C as a therapeutic target. Clin Cancer Res 12 5336-5345... 

From these studies it is clear that the progression of PAR-based therapy relies upon the future development of new specific agonists and antagonists for PARs 2-4 with much higher potencies than those currently available, with an efficient mode of delivery to target sites. However despite these problems the PARs still rqiresent one of the most attractive therapeutic targets for a number of disease states. 

PI (adenosine) receptors were explored as therapeutic targets before P2 receptors. Adenosine was identified early and is in current use to treat supraventricular tachycardia. A2a receptor antagonists are being investigated for the treatment of Parkinson s disease and patents have been lodged for the application of PI receptor subtype agonists and antagonists for myocardial ischaemia and reperfusion injury, cerebral ischaemia, stroke, intermittent claudication and renal insufficiency. 

Toll-like Receptors. Table 2 Therapeutic Targeting of TLRs... 

Ulevitch RJ (2004) Therapeutics targeting the innate immune system. Nat Rev Immunol 4(7) 512—520... 

Feldmann M, Miani RN (2003) TNF defined as a therapeutic target for rheumatoid arthritis and other autoimmune diseases. Nat Med 9 1245-1250... 

Gabapentin and pregabalin are prescribed in certain epileptic diseases such as absence epilepsy and in neuropathic pain. Their therapeutic target for pain suppression is the a2S-l subunit. 

TABLE 3.2 Important Therapeutic Targets of Opportunity Therapeutic Action... 

Chafila TA, Li N, Garcia-Lloret M. Kim HJ. Nel AE T-cell effector pathways in allergic diseases transcriptional mechanisms and therapeutic targets. J Allergy Chn Immunol 2008 121 812-823 quiz 824-815. 

Polosa R, Holgate ST Adenosine receptors as promising therapeutic targets for drug development in chronic airway inflammation. Curr Drug Targets... 

---