Avadomide (CC 122) is an orally active cereblon modulator. Avadomide modulates cereblon E3 ligase activity and induces apoptosis of diffuse large B-cell lymphoma (DLBCL) cell lines. Avadomide exhibits potent antitumor and immunomodulatory activities^[1][2].

Avadomide inhibits proliferation and induces apoptosis in ABC and GCB DLBCL. In DLBCL cell lines, Avadomide-induced degradation or short hairpin RNA-mediated knockdown of Aiolos and Ikaros correlates with increased transcription of IFN-stimulated genes independent of IFN-α, -β, and -γ production and/or secretion and results in apoptosis in both activated B-cell (ABC) and germinal center B-cell DLBCL.[1]

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Treatment of female CB-17 SCID mice with Avadomide (CC122) at 3 or 30 mg/kg once daily significantly decreased tumor growth in OCI-LY10 ABC-DLBCL (P = .028 and P < .001, respectively) and WSU-DLCL2 GCB-DLBCL derived xenograft models (P < .01) compared with the vehicle control. In a separate study, we assessed the ability of Avadomide (CC122) to promote degradation of Ikaros and Aiolos in vivo. In the 21-day efficacy study of WSU-DLCL2 xenograft transplanted mice, tumors were excised 1, 6, or 24 hours post final dosing. Aiolos and Ikaros expression was interrogated through immunohistochemistry (IHC) and was found to be decreased 64% and 30%, respectively, compared with vehicle within 1 hour of treatment, with a maximal reduction of 94% and 69%, respectively, observed at 6 hours. Aiolos and Ikaros levels partially recovered 24 hours postdosing with protein level within 20% and 34% of vehicle, respectively. The 24-hour postdose Aiolos and Ikaros expression represents the trough compound level following multiple doses of Avadomide (CC122). When the 1-hour time point is compared with the 24-hour postdose time point, there is a significant reduction in Aiolos but not Ikaros expression; however, at the 6-hour time point, both transcription factors are significantly different from the 24-hour time point. Taken together, these data reveal that Avadomide (CC122) inhibited DLBCL tumor growth in vivo and that this activity was associated with the degradation of Aiolos and Ikaros in both ABC- and GCB-DLBCL xenograft models.[1]

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

286.29

C₁₄H₁₄N₄O₃

1015474-32-4

Room temperature in continental US; may vary elsewhere.

DMSO : 33.33 mg/mL (116.42 mM; Need ultrasonic)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.5 mg/mL (8.73 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (8.73 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• [1]. Rasco DW, et al. A First-in-Human Study of Novel Cereblon Modulator Avadomide (CC-122) in Advanced Malignancies. Clin Cancer Res. 2019 Jan 1;25(1):90-98.

  [2]. Hagner, P.R.et al.CC-122, a pleiotropic pathway modifier, mimics an IFN response and has antitumor activity in DLBCL.Blood.Aug 6;126(6):779-89.

Female SCID mice (CB17/Icr-Prkdcscid, Charles River) were 8 weeks old, with body weights ranging from 15.0 to 23.2 g, on day 1 of these studies. Each SCID mouse was injected subcutaneously in the right flank with 5×106 OCI-LY10 cells (0.2 ml cell suspension). Tumors were calipered in two dimensions to monitor growth as their mean volume approached 100–150 mm3 . Fourteen days (WSU-DLCL2) or twenty-one days (OCI-LY10) after tumor cell implantation, mice were sorted into treatment groups (n=10/group). Tumors were callipered twice weekly during the study. Avadomide (CC122) was suspended in 0.5% carboxymethyl cellulose: 0.25% Tween-80 in de-ionized water. Vehicle and Avadomide (CC122) were each administered via oral gavage (p.o.) once daily for twenty-eight days (qd x28). [1]

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Rasco DW, et al. A First-in-Human Study of Novel Cereblon Modulator Avadomide (CC-122) in Advanced Malignancies. Clin Cancer Res. 2019 Jan 1;25(1):90-98.

  [2]. Hagner, P.R.et al.CC-122, a pleiotropic pathway modifier, mimics an IFN response and has antitumor activity in DLBCL.Blood.Aug 6;126(6):779-89.