Cereblonmodulator1(compoundF)是一种cereblon(CRBN)E3连接酶调节剂。Cereblonmodulator1与CRBN特异性结合，从而影响泛素E3连接酶复合物的活性。这导致某些底物蛋白的泛素化并诱导蛋白酶体介导的某些转录因子的降解，包括Ikaros(IKZF1)和Aiolos(IKZF3)。
货号:ajcx30366
CAS:1860875-51-9
分子式:C22H18ClF2N3O4
分子量：461.85
溶解度:DMSO: 250 mg/mL (541.30 mM)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

Cereblon modulator 1 (compound F) is a cereblon (CRBN) E3 ligase modulator. Cereblon modulator 1 specifically binds to CRBN, thereby affecting the activity of the ubiquitin E3 ligase complex. This leads to the ubiquitination of certain substrate proteins and induces the proteasome-mediated degradation of certain transcription factors, including Ikaros (IKZF1) and Aiolos (IKZF3)[1][2].

A different CRBN-binding compound, Cereblon modulator 1 (compound F), that demonstrates anti-proliferative activity in non-AML hematological cancer cell lines (such as multiple myeloma) does not inhibit cell growth in any of the 11 AML cell lines tested, including the ten cell lines that are sensitive to the growth inhibitory activity of Compound D. However, when excess Cereblon modulator 1 is added to KG-1 AML cell cultures in the presence of Compound D, the anti-proliferative activity of Compound D is reduced, presumably due to competition for binding of Compound D to CRBN. The relative impact of Cereblon modulator 1 on the anti-proliferative effect of Compound D progressively increased with increasing concentrations of Cereblon modulator 1. In the presence of 100 µμ Cereblon modulator 1, the potency of Compound D in inhibiting cell growth reduced by approximately 60-fold, and the potency of Compound D in inducing apoptosis reduced by approximately 40-fold[1].

[1]. Ellen Filvaroff, et al. Methods for treating cancer and the use of biomarkers as a predictor of clinical sensitivity to therapies. WO2017120446A1. [2]. CC-90009