SNDX-5613 is a potent selective small molecule inhibitor of the menin-MLL binding interaction that is being developed for the treatment of mixed lineage leukemia rearranged MLLr acute leukemias including acute lymphoblastic leukemia ALL. A new orally bioavailable Menin-MLL inhibitor VTP-50469 appears to promote their differentiation through direct effects on.
Challenges And Opportunities In Targeting The Menin Mll Interaction Future Medicinal Chemistry
Inhibition of the Menin MEN1 and MLL MLL1 KMT2A interaction is a potential therapeutic strategy for MLL-rearranged MLL-r leukemia.
Menin inhibitor clinical trial. The most promising meninMLL inhibitors belong to the thienopyrimidine class and have recently entered phase III clinical trials for treating acute leukemias characterized by MLLKMT2A translocations or NPM1 mutations. Morrison MD Chief Executive Officer of Syndax. Structure-based design yielded the potent highly selective and orally bioavailable small-molecule inhibitor VTP50469.
Several acute myeloid leukemia genetic sub-types converge on high expression of HOX genes critical for their self-renewal. This Phase 12a first-in-human FIH open-label dose-escalation study of KO-539 a menin-MLL KMT2A inhibitor will determine the safety and tolerability of escalating doses using a modified toxicity probability interval mTPI adaptive design when administered to patients with relapsed andor refractory AML. KMT2A and NPM1c -mutant relapsed or refractory RR acute leukemias announced Syndax Pharmaceuticals Inc in a press release.
Here we independently evaluated the pathogenic functions of the menin-MLL interaction in a large set of different cancer models with a potent and selective probe inhibitor BAY-155. Within months of initiating the Phase 12 AUGMENT-101 trial we are excited to present to the cancer research community the first clinical evidence that disrupting the interaction between menin and MLL1 with our potent and selective inhibitor SNDX-5613 can induce response in patients with genetically-defined acute leukemias said Briggs W. JNJ-75276617 is an orally bioavailable potent and selective protein-protein interaction inhibitor of the binding between histone-lysine N-methyltransferase 2A KMT2A also called mixed-lineage leukemia 1 MLL1.
We characterized the inhibition of the menin-MLL interaction for anti-proliferation gene transcription effects and for efficacy in several in vivo xenografted tumor models. DS-1594 is a potent and selective small molecule menin inhibitor in clinical development in the Alpha portfolio of Daiichi Sankyo. KOMET-001 Kura Oncology Menin Inhibitor Trial is a Phase 12A clinical trial to determine the safety tolerability and recommended Phase 2 dose of.
KOMET-001 Kura Oncology Menin Inhibitor Trial is a phase 12a study to determine the safety tolerability and recommended phase 2 dose RP2D of KO-539 in patients with refractory or relapsed acute myeloid leukemia AML. In the phase 12 AUGMENT-101 clinical trial NCT04065399 treatment with the novel menin-MLL small molecule inhibitor SNDX-5613 led to robust clinical responses in patients with mixed lineage leukemia rearranged MLL r. Cell lines carrying MLL rearrangements were selectively responsive to VTP50469.
The Companys pipeline is also highlighted by KO-539 a potent and selective menin inhibitor currently in a Phase 12A clinical trial KOMET-001. Morrison MD Chief Executive Officer of Syndax. In addition tipifarnib is being evaluated in multiple other Phase 2 clinical trials in solid tumor and hematologic indications.
DS-1594 was designed to target and disrupt the protein-protein interaction of menin and MLL to inhibit leukemic cell growth and proliferation. Kura Oncology Doses First Patient in Phase 1 Clinical Trial of Menin-MLL Inhibitor KO-539 in Acute Myeloid Leukemia September 16 2019 at 730 AM EDT KO-539 is a first-in-class small molecule inhibitor of the menin-MLL interaction First-in-human trial to determine MTD expand to genetic subgroups such as NPM1. Prognosis is poor in patients with KMT2A rearrangements and in those with co-mutations that may include NPM1About KOMET-001KOMET-001 Kura Oncology Menin Inhibitor Trial is.
An expansion phase in specific genetic subgroups will further evaluate antitumor activity and tolerability. Phase 1 Phase 2. Within months of initiating the Phase III Augment-101 trial we are excited to present to the cancer research community the first clinical evidence that disrupting the interaction between menin and MLL1 with our potent and selective inhibitor SNDX-5613 can induce a response in patients with genetically-defined acute leukemias noted Briggs W.
Wild-type and fusion and menin with activity in leukemic cell lines and primary leukemia patient or patient-derived samples with either KMT2A alterations including gene. Within months of initiating the Phase 12 AUGMENT-101 trial we are excited to present to the cancer research community the first clinical evidence that disrupting the interaction between menin.
