Mcl-1 inhibitor 6 是一种口服有效的，选择性的骨髓细胞白血病 1 (Mcl-1) 蛋白抑制剂，Kd值为 0.23 nM，Ki值为 0.02 μM。Mcl-1 inhibitor 6 对 Mcl-1 的选择性高于其他 Bcl-2 家族成员 (Bcl-2、Bcl2A1、Bcl-xL 和 Bcl-w，Kd>10 μM)。Mcl-1 inhibitor 6 是一种有效的抗肿瘤剂。
| 生物活性 | Mcl-1 inhibitor6 is an orally active, selectivemyeloid cell leukemia 1 (Mcl-1)protein inhibitor with aKdof 0.23 nM and aKiof 0.02 μM.Mcl-1 inhibitor6 possesses superior selectivity over otherBcl-2 familymembers (Bcl-2, Bcl2A1,Bcl-xL, andBcl-w, Kd>10 μM).Mcl-1 inhibitor6 is a potent antitumor agent[1]. |
| IC50& Target[1] | Mcl-1 0.23 nM (Kd) | Mcl-1 0.02 μM (Ki) | Bcl-2 >10 μM (Kd) | Bcl2A1 >10 μM (Kd) | Bcl-xL >10 μM (Kd) | Bcl-W >10 μM (Kd) | Bcl-2 10 μM (Ki) | Bfl-1 1.57 μM (Ki) |
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体外研究
(In Vitro) | Mcl-1 inhibitor 6 has Kis of 10 μM and 1.57μM for Bcl-2 and Bfl-1, respectively[1].
Mcl-1 inhibitor 6 (1, 5 μM; for 48 h) significantly induces apoptosis in a concentration-dependent manner[1].
Mcl-1 inhibitor 6 (0.1, 5 μM; for 4 h) remarkably upregulates PARP cleavage in H929 cells in a concentration-dependent manner[1].
Mcl-1 inhibitor 6 (for 72 h) shows antiproliferative activities against the tumor cell lines (H929, MV4-11, SK-BR-3, NCI-H23; IC50=0.36-3.02 μM). Mcl-1 inhibitor 6 shows ideal selectivity against CML cell line K562 (IC50>30 μM)[1].
Apoptosis Analysis[1] | Cell Line: | H929 cells | | Concentration: | 1, 5 μM | | Incubation Time: | For 48 hours | | Result: | Significantly induced apoptosis in a concentration-dependent manner. |
Western Blot Analysis[1] | Cell Line: | H929 cells | | Concentration: | 0.1, 0.5, 1, 5 μM | | Incubation Time: | For 4 hours | | Result: | Remarkably upregulated PARP cleavage in H929 cells in a concentration-dependent manner. |
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体内研究
(In Vivo) | Mcl-1 inhibitor 6 (compound 40; 60 mg/kg with PO or 20 mg/kg with IP; every two days for 14 days) shows desired in vivo tumor growth inhibition activity[1].
Mcl-1 inhibitor 6 (3 mg/kg with IV or 10 mg/kg with PO) has a T1/2of 2.3 hours, a CL of 15.18 mL/minokg by IV[1].
| Animal Model: | Balb/c nude female mice (7 weeks) loaded with MV4-11 xenografts[1] | | Dosage: | 60 mg/kg (PO) or 20 mg/kg (IP) | | Administration: | IP or PO; every two days for 14 days | | Result: | Showed desired in vivo tumor growth inhibition activity (T/C = 37.30% and 5.52% by po and ip administration, respectively). |
| Animal Model: | SD rats (200-250 g)[1] | | Dosage: | 3 mg/kg (IV) or 10 mg/kg (PO) (Pharmacokinetic Analysis) | | Administration: | IV or PO | | Result: | Had a T1/2of 2.3 hours, a CL of 15.18 mL/minokg by IV.
Had a T1/2of 2.1 hours, a CL of 36.8 mL/minokg and a Cmaxof 2012.95 ng/mL. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 100 mg/mL(193.04 mM;ultrasonic and warming and heat to 60℃) 配制储备液 | 1 mM | 1.9304 mL | 9.6521 mL | 19.3043 mL | | 5 mM | 0.3861 mL | 1.9304 mL | 3.8609 mL | | 10 mM | 0.1930 mL | 0.9652 mL | 1.9304 mL |
*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℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 |
