| Identification | Back Directory | [Name]
Acetamide, N-[4-[[2-[4-[6-[(6-acetyl-8-cyclopentyl-7,8-dihydro-5-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]-3-pyridinyl]-1-piperazinyl]-2-oxoethyl]amino]butyl]-2-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]oxy]- | [CAS]
2417408-46-7 | [Synonyms]
YX-2-107
Acetamide, N-[4-[[2-[4-[6-[(6-acetyl-8-cyclopentyl-7,8-dihydro-5-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]-3-pyridinyl]-1-piperazinyl]-2-oxoethyl]amino]butyl]-2-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]oxy]- | [Molecular Formula]
C45H51N11O9 | [MOL File]
2417408-46-7.mol | [Molecular Weight]
889.95 |
| Hazard Information | Back Directory | [Uses]
YX-2-107 is a PROTAC (IC50= 4.4 nM) that selectively degrades CDK6. YX-2-107 effectively inhibits RB phosphorylation and FOXM1 expression in vitro and inhibits the development of Ph+ ALL in rats. YX-2-107 can be used in the study of Ph chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL)[1]. | [in vivo]
YX-2-107 (10 mg/kg; i.p.; single) shows a maximum concentration of 741 nM (150-fold greater than CDK6 degradation IC50), with clearance from the plasma after 4 hours[1].
YX-2-107 (150 mg/kg; i.p.; single daily for 3 days) is pharmacologically active in suppressing Ph+ ALL proliferation in mice[1]. | Animal Model: | NRG-SGM3 mice (Ph+ ALL xenografts model)[1]. | | Dosage: | 150 mg/kg | | Administration: | Intraperitoneal injection; single daily for 3 days | | Result: | Suppressed the percentage of primary Ph+ ALL S-phase cells, the expression of CDK4/6-regulated phospho-RB and, to a lesser degree, FOXM1, and induced the selective CDK6 degradation.
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| Animal Model: | C57BL/6j mice[1]. | | Dosage: | 10 mg/kg | | Administration: | Intraperitoneal injection; single | | Result: | 1.19Pharmacokinetic Parameters of YX-2-107 in C57BL/6j mice [1].
| IP (10 mg/kg) | | Tmax (h) | 0.5 | | Cmax (ng/mL) | 660 | | AUC0-t (ng/mL·h) | 815 | | AUC0-∞ (ng/mL·h) | 987 |
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| [IC 50]
CDK6: 4.4 nM (IC50) | [References]
[1] De Dominici M, et al. Selective inhibition of Ph-positive ALL cell growth through kinase-dependent and -independent effects by CDK6-specific PROTACs. Blood. 2020 Apr 30;135(18):1560-1573. DOI:10.1182/blood.2019003604 |
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