BCL2-targeting or MCL1-targeting bone fide BH3 mimetics currently in clinical trials
| . | . | State of development . | Characteristics . | ||||
|---|---|---|---|---|---|---|---|
| Target molecule . | Developer . | FDA approved . | Developmental phase . | Heme malignancy . | Target Ki* (nM) . | BAX/BAK dependent . | Route . |
| BCL2 | |||||||
| Venetoclax (ABT-199)17 | Abbvie /Genentech | CLL, AML | 3 | MM, NHL, AML, CLL | <<1 | ✓ | Oral |
| S655487 S55746125 | Servier | 1 1 | Multiple CLL, AML | NR ∼1 | NR ✓ | IV Oral | |
| BGB-11417126 | Beigene | 1 | Multiple | <<1 | NR | Oral | |
| APG-2575127 | Ascentage | 1 | CLL, AML, NHL, T-PLL | <<1 | ✓ | Oral | |
| FCN-338128 | Fochon | 1 | CLL, SLL | NR | NR | Oral | |
| BCL2/BCLxL | |||||||
| Navitoclax (ABT-263)9 | Abbvie | 3 | Myelofibrosis | <1/<1 | ✓ | Oral | |
| AZD0466129,130 | Astra Zeneca | 1 | Multiple | NR | ✓ | IV | |
| Pelcitoclax (APG-1252)131,132 | Ascentage | 1/2 | Myelofibrosis | <1/<1 | ✓ | IV | |
| MCL1 | |||||||
| AMG 17619 AMG 39720 | Amgen | 1 | AML, MM Multiple | <<1 <<1 | ✓ | IV Oral | |
| S64315 (MIK665)21 | Servier/Novartis | 1 | AML, MM, NHL | <<1 | ✓ | IV | |
| AZD599122 | Astra Zeneca | 1 | Multiple | <1 | ✓ | IV | |
| ABBV-467 | Abbvie | 1 | MM | NR | NR | IV | |
| PRT1419 | Prelude | 1 | MDS, AML, NHL, MM | NR | NR | Oral | |
| . | . | State of development . | Characteristics . | ||||
|---|---|---|---|---|---|---|---|
| Target molecule . | Developer . | FDA approved . | Developmental phase . | Heme malignancy . | Target Ki* (nM) . | BAX/BAK dependent . | Route . |
| BCL2 | |||||||
| Venetoclax (ABT-199)17 | Abbvie /Genentech | CLL, AML | 3 | MM, NHL, AML, CLL | <<1 | ✓ | Oral |
| S655487 S55746125 | Servier | 1 1 | Multiple CLL, AML | NR ∼1 | NR ✓ | IV Oral | |
| BGB-11417126 | Beigene | 1 | Multiple | <<1 | NR | Oral | |
| APG-2575127 | Ascentage | 1 | CLL, AML, NHL, T-PLL | <<1 | ✓ | Oral | |
| FCN-338128 | Fochon | 1 | CLL, SLL | NR | NR | Oral | |
| BCL2/BCLxL | |||||||
| Navitoclax (ABT-263)9 | Abbvie | 3 | Myelofibrosis | <1/<1 | ✓ | Oral | |
| AZD0466129,130 | Astra Zeneca | 1 | Multiple | NR | ✓ | IV | |
| Pelcitoclax (APG-1252)131,132 | Ascentage | 1/2 | Myelofibrosis | <1/<1 | ✓ | IV | |
| MCL1 | |||||||
| AMG 17619 AMG 39720 | Amgen | 1 | AML, MM Multiple | <<1 <<1 | ✓ | IV Oral | |
| S64315 (MIK665)21 | Servier/Novartis | 1 | AML, MM, NHL | <<1 | ✓ | IV | |
| AZD599122 | Astra Zeneca | 1 | Multiple | <1 | ✓ | IV | |
| ABBV-467 | Abbvie | 1 | MM | NR | NR | IV | |
| PRT1419 | Prelude | 1 | MDS, AML, NHL, MM | NR | NR | Oral | |
Trial data from ClinicalTrials.gov (accessed 2 January 2021). The most advanced trial phase is listed. References are provided where publication has disclosed the chemical structure and function of the compound. NR, not reported.
Ki measures the affinity for the target in a competition assay. As Ki is measured relative to a competitor and the competitors and assay formats are not uniform across drugs, direct comparison of Ki values between the drugs listed is precluded. Therefore, approximations are provided based on cited specific published data. A Ki of 1 nM or less reflects tight binding to the target and potency in competing with BH3-containing proteins.