Table 2.

Overview of Compounds With Activity Against MCL-1 Not Currently Undergoing Clinical Evaluation

Compound	Category/Binding Site	In Vitro Potency	In Vitro or In Vivo Properties
Clinical evaluation not yet under way
VU661013 [60]	MCL-1 inhibition/ destabilizes BIM/MCL-1 association	KI: 97 pM	Growth inhibition in AML cell lines in vitro; dose-dependent decrease in tumor burden in murine models
Compound 42 [102]	Displaces BIM from MCL-1	Ki: 70–300 pM	Tumor regression in murine models
BIM SAHBA [103]	Preferentially displaces BIM from MCL-1	EC50: 2–18 μM	–
Clinical evaluation does not appear to be progressing
Fesik compound 53 [95]	Inhibition of MCL-1/BH3 peptide binding	KI: 0.055 μM	–
A-1210477 [50, 94]	Inhibition of MCL-1/disrupts BIM binding	KI: 0.0004–0.0005 μM	–
Zhang compound 12 [92]	Inhibition of MCL-1/BH3 peptide binding	KI: 0.48 μM IC50: 2.2μM	Inhibits MCL-1-dependent cells in vitro
MIM1 [89]	Inhibition of MCL-1/BAK interaction	IC50: 4.2 μM	Induces apoptosis in leukemia cells
UMI-77 [90]	Inhibition of MCL-1/BAK interaction	KI: 0.49 μM	Daily administration (5 d/wk for 2 weeks) significantly inhibited tumor growth in BxPC-3 xenograft mouse model
Roussi compound 2c [98]	Inhibition of MCL-1 activity	KI: 0.46 μM	–
Cardone compound 9 [51]	Inhibition of MCL-1/BH3 peptide binding	IC50: 0.31 μM	High activity against a panel of human-derived cancer cell lines
Compound 34 [97]	Inhibition of MCL-1/disrupts BIM binding	IC50: 6.1 μM	–
Chai compound 7 [93]	Inhibition of MCL-1/BH3 peptide binding	KI: 8 μM	–
Pyridoclax [96]	Inhibition of MCL-1/disrupts BIM binding	–	Sensitizes ovarian cancer cells to BCL-XL inhibition
Liu & Wang A1 [99]	Inhibition of MCL-1/BH3 peptide binding	KI: 0.18 μM	–

AML=acute myeloid leukemia; BH3=BCL-2 homology 3; EC₅₀=half-maximal concentration of drug; IC₅₀=concentration inhibitory to 50% of cells; MCL-1=myeloid cell leukemia sequence 1.