As of January 2020[update], zotiraciclib is being evaluated by
Adastra Pharmaceuticals in two separate Phase 1b clinical trials for the treatment of glioblastoma multiforme (GBM). Zotiracicib is also being developed as a potential treatment for
diffuse intrinsic pontine glioma (DIPG), a rare pediatric cancer. Both forms of brain cancer are characterized by Myc overexpression.[6]
Development
The first Phase 1b clinical trial of zotiraciclib in GBM, sponsored by the
National Cancer Institute (NCI), is a multi-arm, dose-finding study examining zotiraciclib plus dose-dense or metronomic
temozolomide (TMZ) in adults with recurrent
anaplastic astrocytoma and GBM.[9]
Zotiraciclib is also being explored for the treatment of DIPG, a rare pediatric cancer.[citation needed]
References
^
abPasha MK, Jayaraman R, Reddy VP, Yeo P, Goh E, Williams A, et al. (March 2012). "Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent CDK/JAK2/FLT3 inhibitor". Drug Metabolism Letters. 6 (1): 33–42.
doi:
10.2174/187231212800229336.
PMID22372550.
^William AD, Lee AC, Goh KC, Blanchard S, Poulsen A, Teo EL, Nagaraj H, Lee CP, Wang H, Williams M, Sun ET, Hu C, Jayaraman R, Pasha MK, Ethirajulu K, Wood JM, Dymock BW (January 2012). "Discovery of kinase spectrum selective macrocycle (16E)-14-methyl-20-oxa-5,7,14,26-tetraazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8(27),9,11,16,21,23-decaene (SB1317/TG02), a potent inhibitor of cyclin dependent kinases (CDKs), Janus kinase 2 (JAK2), and fms-like tyrosine kinase-3 (FLT3) for the treatment of cancer". Journal of Medicinal Chemistry. 55 (1): 169–96.
doi:
10.1021/jm201112g.
PMID22148278.
^Blachly JS, Byrd JC, Grever M (April 2016). "Cyclin-dependent kinase inhibitors for the treatment of chronic lymphocytic leukemia". Seminars in Oncology. 43 (2): 265–73.
doi:
10.1053/j.seminoncol.2016.02.003.
PMID27040705.
^Lyle L, Daver N (August 2018). "Current and emerging therapies for patients with acute myeloid leukemia: a focus on MCL-1 and the CDK9 pathway". The American Journal of Managed Care. 24 (16 Suppl): S356–S365.
PMID30132679.
^Clinical trial number NCT02942264 for "Zotiraciclib (TG02) Plus Dose-Dense or Metronomic Temozolomide Followed by Randomized Phase II Trial of Zotiraciclib (TG02) Plus Temozolomide Versus Temozolomide Alone in Adults With Recurrent Anaplastic Astrocytoma and Glioblastoma" at
ClinicalTrials.gov