Recurrent driver mutations in FMS-related receptor tyrosine kinase 3 (FLT3) occur in around one-third of patients with de novo acute myeloid leukemia (AML). Although most FLT3 mutations are secondary events in leukemogenesis, they are associated with accelerated clonal expansion and disease progression, and treatment with the tyrosine kinase inhibitor midostaurin has been shown to increase patients’ long-term survival. However, the efficacy of FLT3 inhibitors in eliminating FLT3-mutated clones is variable.
Finding suitable antigens for immunotherapy of myeloid malignancies, particularly acute myeloid leukemia (AML), is an urgent clinical need. Most AML candidate targets, including CD123, are co-expressed by hematopoietic stem and progenitor cells (HSCPs), with the subsequent risk of myelosuppression associated with myeloid cell-targeted chimeric antigen receptor (CAR) T therapy.
Syndax Pharmaceuticals Inc. is gearing up for a U.S. FDA filing by the end of 2023 on the back of positive data from a pivotal phase I/II study testing menin inhibitor revumenib in adult and pediatric patients with relapsed/refractory KMT2A-rearranged acute myeloid leukemia and acute lymphoid leukemia.
Researchers from Fudan University and affiliated organizations presented the discovery of novel PIM kinase inhibitors for the treatment of acute myeloid leukemia (AML). A literature-aided molecular hybridization strategy was applied to synthesize a structurally novel compound, based on an N-pyridinyl amide scaffold. Subsequent optimization showed that the positional isomerization of pyridine N toward to Lys67 resulted in a decrease of potency while increased freedom of solvent fragment toward Asp128/Glu171 led to an increase in activity.
Targeting rearranged during transfection (RET) proto-oncogene may be an effective therapeutic strategy for acute myeloid leukemia (AML) patients with mutations in FLT3 and activated RET. However, few RET-targeting agents have been approved for clinical use, and no FLT3/RET dual-targeting drugs have been identified.
Hoth Therapeutics Inc. has reported promising results from sponsored preclinical research conducted at NC State University (NCSU) with HT-KIT, the company’s new molecular entity for the treatment of advance systemic mastocytosis. HT-KIT is an antisense oligonucleotide that targets the proto-oncogene c-Kit by inducing mRNA frame shifting.
Sichuan Haisco Pharmaceutical Co. Ltd. has described N6-adenosine-methyltransferase catalytic subunit (METTL3) inhibitors reported to be useful for the treatment of cancer.
A Pelemed Co. Ltd. patent details new indirubin derivatives acting as inhibitors of FLT3 (FLK2/STK1) and/or proto-oncogene tyrosine-protein kinase receptor Ret (RET; CDHF12; PTC) and its mutants. They are reported to be useful for the treatment of acute myeloid leukemia.
Xnk Therapeutics AB has entered into a research collaboration with the Karolinska University Hospital to evaluate the suitability of the company's preclinical autologous natural killer (NK) cell therapy candidate XNK-02 as a novel therapy for treatment of acute myeloid leukemia (AML).