Table 2.
Promising mimetics and inhibitor therapeutic agents for cancer
| Agent | Type | Origins | Target | Off-Target | Developer | Ref |
|---|---|---|---|---|---|---|
| ABT-737 | BH3-M |
Structure-based design, BAK peptide |
Bcl-2, Bcl-xL | – | Abbott Labs. (IL, USA) | [58] |
| Navitoclax | BH3-M | ABT-737 | Bcl-2, Bcl-xL, Mcl1 | Mcl1 (weak) | Abbott Labs. (IL, USA) | [59] |
|
Gossypol (AT-101) |
BH3-M |
Structure-based design, BIM peptide |
Bcl-2, Bcl-xL, Mcl1 | – | University of Michigan (MI, US) | [60] |
| Obatoclax | BH3-M | In silico docking studies | Bcl-2, Mcl1 | Bcl-xL | University of Montreal (CAN) | [61] |
| Venetoclax | BH3-M | Navitoclax | Bcl-2 | Bcl-xL (weak) | AbbieVie (IL, USA) | [62] |
| Compound 3 | Smac-M |
Smac (AVPI/AVPF peptide sequence) |
xIAP, cIAP1/2 | NF-κB activation | University of Texas (TX, USA) |
[63] [64] |
| APG1387 | Smac-M | Smac (AVPI peptide sequence) | xIAP, cIAP1/2 | – | University of Michigan (MI, USA) | [65] |
| AT-406 | Smac-M | Structure-based design | xIAP, cIAP1/2 | – | University of Michigan (MI, USA) | [66] |
| Compound A | Smac-M | Small molecule screen | xIAP, cIAP1/2 | – | University of Texas (TX, USA) | [63] |
| LC161 | Smac-M | Structure-based design | xIAP, cIAP1/2 | – | Dana-Farber CI (MA, US) | [67] |
| SM-164 | Smac-M | Structure-based design | xIAP | – | University of Michigan (MI, USA) | [68] |
| Birinapant | Smac-M | Smac (AVPI peptide sequence) | cIAP1 | xIAP (weak) | Duke University (NC, USA) | [69] |
| A1210477 | Mcl1-I | High throughput screen | Mcl1 | – |
AbbieVie (IL, USA) Genetech (CA, US) |
[70] [71] |
| AMG-176 | Mcl1-I |
Structure-based design, High throughput screen |
Mcl1 | Bcl-2, Bcl-xL (minimal) | Amgen (CA, USA) | [72] |
| AZD-5991 | Mcl1-I | Structure-based design | Mcl1 | – | AstraZeneca (MA, US) | [73] |
| S63845 | Mcl1-I | In-silico modelling | Mcl1 | – | Institut de Recherches Servier Oncology (FRA) | [74] |
| MIM1 | Mcl1-I | Small molecule screen | Mcl1 | – | Dana-Farber CI (MA, USA) | [75] |
| VU661013 | Mcl1-I | Structure-based design | Mcl1 | BIM-Mcl1 destabilization | Vanderbilt University (TN, USA) |
[76] [77] |
| GDC-0941 | Mcl1-I | In-silico modelling | PI3Kα/δ, Mcl1 | – | Piramed Pharma (UK) | [78] |
BH3-mimetics (-M), Smac-mimetics (-M) and Mcl1 inhibitors (-I) are highlighted along with the techniques utilized for their discovery or origins. For each drug, we show its cognate target and off-target proteins or effects, its developer and the publication describing its development (Ref)