Table 2.

A list of prominent SMAC mimetics, their indications for therapeutic strategies in specific cancers, suggested combinatorial approaches and clinical trials conducted to date [39–91, 93–108]

SMAC mimetic	Target	Cancers in vitro	Potential combinatory therapies	Clinical trials
AT-406	XIAP, cIAP1, cIAP2 [93]	Ovarian cancer [109], solid tumors (including breast, head and neck) [94], colorectal cancer [35]	Carboplatin, cisplatin and paclitaxel [109], radiation therapy [96], TRAIL, Bcl-2 and BRAF inhibitors [95]	Phase II, single agent, ovarian cancer (Debiopharm), Phase I acute myelogenous leukemia (AML) (terminated), Phase I (completed in 2014), Dose escalation study (Debiopharm), Phase l/lb non-small cell lung cancer (2016, Debiopharm, Merk and Phizer)
LCL-161	Degradation of cIAP1 and cIAP2 [97, 98]	Multiple myelofibrosis, solid tumors (including breast and ovarian) [99], esophageal squamous cell carcinoma [97], non-small cell lung cancer [98]	TNF- α/TRAIL [99], radiation therapy [97], paclitaxel [110, 98]	Phase II, LCL161 adjunct to cyclophosphamide for multiple myeloma (Ongoing-Mayo Clinic), Phase II, single agent, multiple myelofibrosis (2016, ongoing M.D. Anderson Cancer Center and Novartis), Phase II LCL161 adjunct to paclitaxel for triple-negative breast cancer (completed in 2014, Novartis Pharmaceuticals), Phase I LCL161 adjuct to PDR001 for colorectal, triple-negative breast cancer and (2016, ongoing Novartis Pharmaceuticals)
GDC-0152	XIAP, cIAP1, cIAP2 and ML-lAP [100, 101]	Breast cancer [100], glioblastoma [101]	No information	Phase 1 solid cancers (completed in 2010, Genetech)
BIRINAPANT	Degradation of cIAP1 and cIAP2 [102]	Breast cancer [103], ovarian cancer [104], solid tumours [105], melanoma [106]	Carboplatin [104], TRAIL [102, 103], TNF-α [106]	Phase II ovarian cancer, single agent (completed 2015, National Cancer Institute), Phase I lymphoma, dose escalation study (completed 2013, TetraLogic Pharmaceuticals), Phase Ib, ovarian and peritoneal cancer, Birinapant adjunct to conatumumab (Completed 2015, TatraLogic Pharmaceuticals), Phase Ib/2a, myelodysplastic syndrome, birinapant adjuct to 5-azacitidine (completed 2015, TetraLogic Pharmaceuticals), Phase II, advanced or recurrent high grade carcinoma, birinipant adjuct to platinum based agents (initiated 2017, Jonsson Comprehensive Cancer Center and TetraLogic Pharmaceuticals). Phase I/II, solid tumors, dose escalation study in combination with pembrolizumab (initiated 2017, TetraLogic Pharmaceuticals)
HGS-1029	XIAP inhibition, loss of cIAP expression [111]	Advanced solid tumors (including colon, andrenocarcinoma) (TetraLogic Pharmaceuticals)	No information	Phase I, single agent for solid tumors (completed in 2012, Aegera Therapeutics)
BV6	XIAP, cIAP1 and cIAP2 [107, 108]	Breast cancer [112], acute myeloid leukemia (AML) [107], childhood ALL [108]	Drozitumab [112], 5-azacytidine [107], dexamethasone [108]	N/A