Saracatinib

Saracatinib
Clinical data
Routes of
administration		 Oral
Legal status
Legal status
  • Investigational
Identifiers
CAS Number 379231-04-6
PubChem (CID) 10302451
ChemSpider 8477917
Chemical and physical data
Formula C27H32ClN5O5
Molar mass 542.025 g/mol
3D model (Jmol) Interactive image

Saracatinib (AZD-0530) is an experimental drug being developed by AstraZeneca. It acts as a dual kinase inhibitor, with selective actions as a Src inhibitor and a Bcr-Abl tyrosine-kinase inhibitor.[1][2] It was originally under development for the treatment of cancer, but while it appeared promising in animal studies and was well tolerated in humans, it failed to show sufficient efficacy in cancer patients and was ultimately not developed further for this application. However saracatinib has subsequently been researched for other applications such as Alzheimer's disease. AZD0530 is an inhibitor of Src and Abl family kinases1. It has been developed as treatment for malignancies because these kinases play a role in tumor invasion and proliferation. However, the Src family kinases (SFKs) are highly expressed in brain and have major effects on synaptic plasticity2. Moreover, the investigators have recently shown that a specific SFK, namely Fyn, is aberrantly activated by specific conformations of the Amyloid Beta (Aß) peptide from Alzheimer's disease (AD). Genetic deletion of Fyn rescues AD deficits in preclinical models. This clinical trial will test the potential benefit of AZD0530 for Alzheimer's disease modification.[3][4] [5][6] and schizophrenia.[7]

See also

References

  1. ↑ Hennequin LF, Allen J, Breed J, Curwen J, Fennell M, Green TP, Lambert-van der Brempt C, Morgentin R, Norman RA, Olivier A, Otterbein L, Plé PA, Warin N, Costello G. N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a novel, highly selective, orally available, dual-specific c-Src/Abl kinase inhibitor. J Med Chem. 2006 Nov 2;49(22):6465-88. PMID 17064066
  2. ↑ Schenone S, Brullo C, Musumeci F, Botta M. Novel dual Src/Abl inhibitors for hematologic and solid malignancies. Expert Opin Investig Drugs. 2010 Aug;19(8):931-45. doi: 10.1517/13543784.2010.499898 PMID 20557276
  3. ↑ Gubens MA, Burns M, Perkins SM, Pedro-Salcedo MS, Althouse SK, Loehrer PJ, Wakelee HA. A phase II study of saracatinib (AZD0530), a Src inhibitor, administered orally daily to patients with advanced thymic malignancies. Lung Cancer. 2015 Jul;89(1):57-60. doi: 10.1016/j.lungcan.2015.04.008 PMID 26009269
  4. ↑ Reddy SM, Kopetz S, Morris J, Parikh N, Qiao W, Overman MJ, Fogelman D, Shureiqi I, Jacobs C, Malik Z, Jimenez CA, Wolff RA, Abbruzzese JL, Gallick G, Eng C. Phase II study of saracatinib (AZD0530) in patients with previously treated metastatic colorectal cancer. Invest New Drugs. 2015 Aug;33(4):977-84. doi: 10.1007/s10637-015-0257-z PMID 26062928
  5. ↑ Kaufman AC, Salazar SV, Haas LT, Yang J, Kostylev MA, Jeng AT, Robinson SA, Gunther EC, van Dyck CH, Nygaard HB, Strittmatter SM. Fyn inhibition rescues established memory and synapse loss in Alzheimer mice. Ann Neurol. 2015 Jun;77(6):953-71. doi: 10.1002/ana.24394 PMID 25707991
  6. ↑ Nygaard HB, Wagner AF, Bowen GS, Good SP, MacAvoy MG, Strittmatter KA, Kaufman AC, Rosenberg BJ, Sekine-Konno T, Varma P, Chen K, Koleske AJ, Reiman EM, Strittmatter SM, van Dyck CH. 'Alzheimers Res Ther. 2015 Apr 14;7(1):35. doi: 10.1186/s13195-015-0119-0. PMID 25874001
  7. ↑ MICA: SRC inhibitors as potential antipsychotics: human testing with psilocybin. Imperial College London. 27 July 2015
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