Mcl-1 inhibitor 6 is an orally active, selective myeloid cell leukemia 1 (Mcl-1) protein inhibitor with a Kd of 0.23 nM and a Ki of 0.02 μM. Mcl-1 inhibitor 6 possesses superior selectivity over other Bcl-2 family members (Bcl-2, Bcl2A1, Bcl-xL, and Bcl-w, Kd>10 μM). Mcl-1 inhibitor 6 is a potent antitumor agent[1].
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. |
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 T1/2 of 2.3 hours, a CL of 15.18 mL/min•kg 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 T1/2 of 2.3 hours, a CL of 15.18 mL/min•kg by IV. Had a T1/2 of 2.1 hours, a CL of 36.8 mL/min•kg and a Cmax of 2012.95 ng/mL. |