Simultaneous inhibition of phosphoinositide 3-kinase (PI3K) and histone deacetylase (HDAC) is considered a good strategy in cancer treatment, although current PI3K/HDAC dual inhibitors have limitations, such as low selectivity and moderate toxicity levels.
Myeloproliferative neoplasms (MPNs) are a group of disorders of which the main hallmarks are bone marrow fibrosis and atypical megakaryocytes (MK) accumulation. Both Rho kinase (ROCK) and Aurora kinase (ARK) pathways are involved in correct MK maturation.
A new degrader strategy has been previously proposed to mitigate platelet toxicity associated with Bcl-xL degraders. This strategy consists of selectively degrading Bcl-xL by the von Hippel-Lindau protein (VHL) E3 ligase in tumor cells, but not in platelets, which minimally express VHL. DT-2216 was developed as the first Bcl-xL degrader of this kind; however, this clinical candidate has still shown some platelet toxicity in vivo.
With an initial €8 million (US$8.4 million) in seed funding in the bank, Tessellate Bio has emerged from stealth to tackle cancers that rely on the less well explored synthetic lethality mechanism of alternative lengthening of telomeres.
Wall Street will be watching closely for such adverse effects as anemia that foiled Gilead Sciences Inc.’s CD47-binding magrolimab earlier this year, but so far Shattuck Labs Inc.’s SL-172154 looks strong in combination with azacitidine to treat front-line higher-risk myelodysplastic syndrome (HR-MDS) and TP53-mutant (TP53m) acute myeloid leukemia (AML).
Immuneering Corp. has obtained FDA clearance of its IND application for IMM-6-415, an oral, twice-daily small molecule in development for the treatment of advanced RAF or RAS mutant solid tumors.
Repare Therapeutics Inc. has identified membrane-associated tyrosine- and threonine-specific Cdc2-inhibitory kinase (PKMYT1) inhibitors reported to be useful for the treatment of cancer.
Shinobi Therapeutics Inc. has closed a $51 million series A financing. The company is developing a new class of off-the-shelf immune evasive iPSC-derived cell therapies.
Gigagen Inc., a subsidiary of Grifols SA, has received clearance from the FDA of its IND application to conduct a phase I trial of GIGA-564 for the treatment of solid tumors.
The inhibition of cyclin-dependent kinase 4 (CDK4) and CDK6 is a useful strategy to treat hormone receptor (HR)+/HER2+ breast cancer, but patients may develop resistance through different mechanisms. As reported at the recent San Antonio Breast Cancer Symposium, researchers from Biotheryx Inc. have synthesized a new CDK4/6 degrader – BTX-9341 – to address the problem of therapeutic resistance in breast cancer.
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