Gspt1 toxicity
WebJun 2, 2024 · GSPT1 loss results in activation of the integrated stress response (ISR), inhibition of nonsense-mediated decay (NMD), and induction of apoptosis. Aims To … WebJan 22, 2024 · Among these, GSPT1, a translation termination factor, is probably the most concerning neosubstrate, which may be degraded by CRBN-recruiting PROTACs because of the critical role of GSPT1 in most ...
Gspt1 toxicity
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WebJan 17, 2024 · ORM-5029, the latest disclosed DAC or Antibody neoDegrader Conjugate (AnDC™), aims to deliver a GSPT1 degrader (Smol006) to HER2-expressing cells via pertuzumab. This AnDC™ has demonstrated stronger cytotoxicity than other GSPT1 degraders and anti-tumor activity comparable to that of DS-8201a . The toxicity of ORM … WebNov 11, 2024 · The trial hit one dose-limiting toxicity — a case of grade 2 pancreatitis at the fifth-highest dose level. The most common treatment-emergent adverse events were infusion-related reactions, back ...
WebNov 15, 2024 · Prior reports of small-molecule GSPT1 degraders such as CC-90009 in AML demonstrate potent anti-tumor cytotoxicity, but with a potentially narrow therapeutic index. ... ORM-6151 showed minimal cytotoxic activity to healthy hematopoietic progenitor cells, with 10-10,000 fold less toxicity than CC-90009 or Mylotarg. We evaluated ORM-6151 in ... WebTest article CC-325 is a potent oral cereblon (CRBN) modulator that has shown potent G1 to S phase transition 1 (GSPT1) degradation and anti-tumor activity in pre-clinical models. …
WebFeb 4, 2024 · This study represents an extension of the investigators’ previous article in which they described the precursor CBRN modulator CC-885, which also targeted GSPT1, as well as multiple other substrates. 2 The clinical development of this agent was … WebJan 1, 2024 · low toxicity in vivo suggesting that higher doses or com-bination with other treatments might be suitable for. future treatments in MYC-driven malignancies. 86. Inhibition of PIM1 kinase.
WebJun 5, 2024 · Distinct patterns of substrate specificity may explain the diversity in clinical activity and toxicity of these drugs. For example, degradation of CK1α is a key event for …
WebMar 24, 2024 · CC-885, a novel thalidomide derivative, exhibited potent anti-solid tumor efficacy via the specific degradation of the translation termination factor GSPT1 . … clapton warehouseWebSep 30, 2024 · Since GSPT1 plays a key role in most cells, GSPT1 may be degraded by the PROTACs recruited to CRBN and has potential toxicity . For the first time, it was … downlights living roomWebAlthough CC-885 can promote apoptosis and the subsequent death of lenalidomide-insensitive cells, it exhibits toxicity and poor specificity for protein degradation. CC-90009, a compound that induces the degradation of GSPT1, has demonstrated increased selectivity against non-cancer cells and lower toxicity [30]. clapton universityWebJan 9, 2024 · CC-885 may thus have a potential for AML therapy different from other IMiDs. As CC-885 can induce the degradation of GSPT1 while other IMiDs do not, it may have … clapton\\u0027s nicknameWebJun 5, 2024 · Distinct patterns of substrate specificity may explain the diversity in clinical activity and toxicity of these drugs. For example, degradation of CK1α is a key event for lenalidomide efficacy in del(5q) MDS , while GSPT1 degradation is deemed to account for anti-AML activity of CC-885 and CC-90009 [25, 28]. downlight smallWebOct 16, 2024 · We screened the library for CRBN-dependent antiproliferative activity in the multiple myeloma cell line MM1.S and identified five hit compounds. Quantitative … downlights loft insulationWebJun 4, 2024 · BTX-1188 could prevent systemic inflammatory dose-limiting toxicities that are usually attributed to pure GSPT1 degradation due to its immunomodulatory properties from the IKZF1/3 degradation. Preclinical data demonstrated potential for using the first-in-class oral molecular glue BTX-1188 in patients with solid tumors or acute myeloid leukemia ... clapton university in south carolina