Aceh Pharmaceutical MDM2-p53 inhibitors in a joint Bcl-2 inhibitor Phase 2a clinical study was approved in China and the United States

Synthetic lethality is the simultaneous suppression of two non-lethal genes, leading to cell death.
this mechanism to find specific mutations in tumors, and then to find its "synthetic lethal partner", and then specifically kill cancer cells, triggering the tumor community's infinite vision.
previously, PARP inhibitors that use the concept of synthetic lethality to fight cancer have been clinically successful, which also gives some confidence to the development of new drugs in the field of synthetic lethal mechanisms.
this clinical trial is a global multi-center, open, Phase 2a clinical study designed to evaluate the safety, pharmacological dynamics, and initial efficacy of APG-115 monodring or combined APG-2575 treatment for patients with relapsed/difficult-to-treat T-PLL.
, APG-115 is an oral bioavailable, highly selective small molecule MDM2 inhibitor that restores p53 tumor inhibition activity by blocking MDM2-p53 interactions.
APG-2575 is a new type of oral Bcl-2 selective small molecule inhibitor, by selectively inhibiting Bcl-2 protein to restore the tumor cell program death mechanism (apoptosis), so as to achieve the treatment of blood and solid tumors.
APG-2575 and APG-115 are important varieties of ASA Pharmaceutical apoptosis product pipelines, both oral targeted drugs, and are expected to achieve chemotherapy-free ( chemo-free) with high clinical application value.
combination of drugs is the future development trend of tumor therapy, and the combination of APG-115 and APG-2575 can stimulate the "synthetic death" mechanism in a variety of cancers, that is, block tumor cells to escape apoptosis MDM2-TP53 and BCL-2 two key path, resulting in tumor cells no way to escape, and then die, with great clinical significance.
It is worth mentioning that in multiple human hematostoma or solid tumor cell line (CDX) and PDX models, APG-115 and APG-2575 have shown a high degree of synergy and significantly enhanced anti-tumor activity.
the drug achieved a 100% remission rate in animal models carrying acute myeloid leukemia (AML, MV-4-11) and hypertrocytic leukemia (MCL, Z138) xeno-transplant tumors.
T-PLL is invasive T lymphoblastic leukemia, which is clinically rare and has very limited treatment options.
patients with relapsed T-PLL had poor prognostication, with a total survival of only 6 to 9 months.
there are still large and unsolt clinical needs for effective treatment of T-PLL.
source: Medical Mission Hills