Table 1 Examples of UPR-targeted cancer drugs in development
From: Unfolded protein response in cancer: the Physician's perspective
Drug | Classification/Mechanism | Development Stage | Disease Indication | Reference |
|---|---|---|---|---|
Bortezomib | Proteasome inhibitor | FDA approved | Multiple myeloma, mantle-cell lymphoma | San et al. [97] |
NPI-0052 (salinosporamide A) | Irreversible proteasome inhibitor | Phase I clinical trials | Multiple Myeloma, Advanced malignancies | Chauhan et al. [98] |
Carfilzomib (PR-171) | Selective proteasome inhibitor | Phase I, II, III clinical trials | Multiple Myeloma, Waldenstrom's Macroglobulinemia | |
PS-341 | Selective proteasome inhibitor | Phase II | Multiple Myeloma | Richardson et al. [101] |
CEP-18770 | Proteasome inhibitor | Phase I, II clinical trials and preclinical studies | multiple myeloma, Non- Hodgkin's lymphoma | Piva et al. [102] |
Tanespimycin (17-AAG, (17-Allylamino-17-demethoxygeldanamycin), KOS-953) | HSP90 Inhibitor | Phase I, II, III clinical trials | Gastrointestinal stromal tumors, breast cancer, gynecological, leukemia, lymphoma, melanoma, prostate, renal, thyroid carcinoma, melanoma | Richardson et al. [103, 104] Heath et al. [105] Pacey et al. [106] |
Alvespimycin (KOS-1022, 17-DMAG) | HSP90 Inhibitor | Phase I clinical trials and preclinical studies | Acute myeloid leukemia, advanced carcinoma | Kummar et al. [107] Lancet et al. [108] Pamanathan et al. [109] Zismanov et al. [110] |
Retaspimycin (IPI-504) | HSP90 Inhibitor | Phase II clinical trials | Gastrointestinal stromal tumors, nonsmall cell lung, prostate | Hanson et al. [111] |
PU-H71 | HSP90 Inhibitor | Preclinical studies | Breast cancer, myeloma, myeloproliferative disorder | Usmani et al. [84] Caldas-Lopes et al. [112] Marubayashi et al. [113] |
SNX-2112 | HSP-90 inhibitor | Preclinical studies | Gastric cancer | Bachleitner-Hofmann, et al. [114] |
Eeyarestatin I (EerI) | Inhibitor of ER-associated degradation (ERAD) | Preclinical studies | Â | Cross et al. [115] |
Versipelostatin | GRP78 inhibitor | Preclinical studies | Â | Matsuo et al. [87] |
(-)-epigallocatechin gallate (EGCG) | GRP78 inhibitor | Preclinical studies | Breast carcinoma | Luo et al. [116] |
Epidermal growth factor (EGF)-SubA | GRP78-targeting cytotoxin | Preclinical murine animal models | Prostate tumor | Backer et al. [90] |
Irestatins | IRE1α inhibitor | Preclinical studies | Multiple Myeloma, | Feldman et al. [117] |
Delta(9)-Tetrahydrocannabinol (THC) | Cannabinoid, activates ER stress and autophagy | Phase I clinical trial | Glioblastoma multiforme | Guzmán et al. [118] |