Page 26 - GPD-4-3

Gene & Protein in Disease Targeting cathepsins during cancer development

140. Park CM, Oie T, Petros AM, et al. Design, synthesis, and 150. Leverson JD, Zhang H, Chen J, et al. Potent and selective
computational studies of inhibitors of Bcl-xL. J Am Chem small-molecule MCL-1 inhibitors demonstrate on-target
Soc. 2006;128(50):16206-16212. cancer cell killing activity as single agents and in
combination with ABT-263 (navitoclax). Cell Death Dis.
doi: 10.1021/ja0650347
2015;6(1):e1590.
141. Wang G, Nikolovska-Coleska Z, Yang CY, et al. Structure-
based design of potent small-molecule inhibitors of anti- doi: 10.1038/cddis.2014.561
apoptotic Bcl-2 proteins. J Med Chem. 2006;49(21):6139-6142. 151. Bruncko M, Wang L, Sheppard GS, et al. Structure-guided
design of a series of MCL-1 inhibitors with high affinity and
doi: 10.1021/jm060460o
selectivity. J Med Chem. 2015;58(5):2180-2194.
142. Nguyen M, Marcellus RC, Roulston A, et al. Small molecule
obatoclax (GX15-070) antagonizes MCL-1 and overcomes doi: 10.1021/jm501258m
MCL-1-mediated resistance to apoptosis. Proc Natl Acad Sci 152. Caenepeel S, Brown SP, Belmontes B, et al. AMG 176, a
U S A. 2007;104(49):19512-19517. selective MCL1 inhibitor, is effective in hematologic cancer
models alone and in combination with established therapies.
doi: 10.1073/pnas.0709443104
Cancer Discov. 2018;8(12):1582-1597.
143. Li L, Thomas RM, Suzuki H, De Brabander JK, Wang X,
Harran PG. A small molecule Smac mimic potentiates doi: 10.1158/2159-8290.CD-18-0387
TRAIL- and TNFalpha-mediated cell death. Science. 153. Tron AE, Belmonte MA, Adam A, et al. Discovery of
2004;305(5689):1471-1474. Mcl-1-specific inhibitor AZD5991 and preclinical activity
in multiple myeloma and acute myeloid leukemia. Nat
doi: 10.1126/science.1098231
Commun. 2018;9(1):5341.
144. Bai L, Chen W, Chen W, Wang X, Tang H, Lin Y. IKKbeta-
mediated nuclear factor-kappaB activation attenuates smac doi: 10.1038/s41467-018-07551-w
mimetic-induced apoptosis in cancer cells. Mol Cancer Ther. 154. Kotschy A, Szlavik Z, Murray J, et al. The MCL1 inhibitor
2009;8(6):1636-1645. S63845 is tolerable and effective in diverse cancer models.
Nature. 2016;538(7626):477-482.
doi: 10.1158/1535-7163.MCT-09-0068
doi: 10.1038/nature19830
145. Lu J, Bai L, Sun H, et al. SM-164: A novel, bivalent Smac
mimetic that induces apoptosis and tumor regression by 155. Stewart ML, Fire E, Keating AE, Walensky LD. The MCL-1
concurrent removal of the blockade of cIAP-1/2 and XIAP. BH3 helix is an exclusive MCL-1 inhibitor and apoptosis
Cancer Res. 2008;68(22):9384-9393. sensitizer. Nat Chem Biol. 2010;6(8):595-601.
doi: 10.1158/0008-5472.CAN-08-2655 doi: 10.1038/nchembio.391
146. Cai Q, Sun H, Peng Y, et al. A potent and orally active 156. Ramsey HE, Fischer MA, Lee T, et al. A novel MCL1
antagonist (SM-406/AT-406) of multiple inhibitor of inhibitor combined with venetoclax rescues venetoclax-
apoptosis proteins (IAPs) in clinical development for cancer resistant acute myelogenous leukemia. Cancer Discov.
treatment. J Med Chem. 2011;54(8):2714-2726. 2018;8(12):1566-1581.
doi: 10.1021/jm101505d doi: 10.1158/2159-8290.CD-18-0140
147. Weisberg E, Ray A, Barrett R, et al. Smac mimetics: 157. Lee T, Bian Z, Zhao B, et al. Discovery and biological
Implications for enhancement of targeted therapies in characterization of potent myeloid cell leukemia-1
leukemia. Leukemia. 2010;24(12):2100-2109. inhibitors. FEBS Lett. 2017;591(1):240-251.
doi: 10.1038/leu.2010.212 doi: 10.1002/1873-3468.12497
148. Sun H, Nikolovska-Coleska Z, Lu J, et al. Design, synthesis, 158. Folkes AJ, Ahmadi K, Alderton WK, et al. The identification
and characterization of a potent, nonpeptide, cell- of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-
permeable, bivalent Smac mimetic that concurrently targets 1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine
both the BIR2 and BIR3 domains in XIAP. J Am Chem Soc. (GDC-0941) as a potent, selective, orally bioavailable
2007;129(49):15279-15294. inhibitor of class I PI3 kinase for the treatment of cancer.
J Med Chem. 2008;51(18):5522-5532.
doi: 10.1021/ja074725f
doi: 10.1021/jm800295d
149. Allensworth JL, Sauer SJ, Lyerly HK, Morse MA, Devi GR.
Smac mimetic Birinapant induces apoptosis and enhances 159. Zamyatnin AA Jr., Gregory LC, Townsend PA, Soond SM.
TRAIL potency in inflammatory breast cancer cells in an Beyond basic research: The contribution of cathepsin B to
IAP-dependent and TNF-alpha-independent mechanism. cancer development, diagnosis and therapy. Expert Opin
Breast Cancer Res Treat. 2013;137(2):359-371. Ther Targets. 2022;26(11):963-977.
doi: 10.1007/s10549-012-2352-6 doi: 10.1080/14728222.2022.2161888

Volume 4 Issue 3 (2025) 15 doi: 10.36922/gpd.4768