lcl161

LCL161 是一种 SMAC 模拟物，一种 IAP 拮抗剂，具有口服活性，抑制 HEK293 细胞中 XIAP (IC50=35 nM)，也抑制 MDA-MB-231 细胞中 cIAP1 (IC50=0.4 nM)。LCL161 具有潜在抗肿瘤活性。

cIAP1 ligand 2, a derivative of LCL161, is an IAP ligand that can be connected to the ABL ligand for protein via a linker, resulting in the formation of SNIPER.

cIAP1 ligand 1 (E3 ligase Ligand 12) 是基于 LCL161 衍生物的细胞凋亡蛋白配体，可募集 IAP 泛素连接酶以降解靶蛋白，可用于和雄激素受体配体欧联开发蛋白降解剂，可用于研究前列腺癌。

SNIPER(ABL)-024, conjugating GNF5 (ABL inhibitor) to LCL161 derivative (IAP ligand) with a linker, induces the reduction of BCR-ABL protein with a DC50 of 5μM[1].

SNIPER(ABL)-033, conjugating HG-7-85-01 (ABL inhibitor) to LCL161 derivative (IAP ligand) with a linker, induces the reduction of BCR-ABL protein with a DC50 of 0.3 μM[1].

SNIPER(ABL)-039, conjugating Dasatinib (ABL inhibitor) to LCL161 derivative (IAP ligand) with a linker, induces the reduction of BCR-ABL protein with a DC50 of 10 nM. IC50s are 0.54 nM, 10 nM, 12 nM, and 50 nM for ABL, cIAP1, cIAP2, XIAP, respectively[1].

SNIPER(ABL)-058, conjugating Imatinib (ABL inhibitor) to LCL161 derivative (IAP ligand) with a linker, induces the reduction of BCR-ABL protein with a DC50 of 10 μM[1].

SNIPER(ER)-87 is a chemical compound composed of a derivative of the inhibitor of apoptosis protein (IAP) ligand LCL161 conjugated to the estrogen receptor α (ERα) ligand 4-hydroxytamoxifen using a PEG linker. It effectively degrades the ERα protein with an IC50 value of 0.097 μM. Within cells, SNIPER(ER)-87 selectively recruits XIAP to ERα, and XIAP functions as the primary E3 ubiquitin ligase responsible for the degradation of ERα induced by SNIPER(ER)-87[1][2].

HG-7-85-01-NH2 是 SNIPER(ABL)-033 的配体。该化合物通过将 HG-7-85-01 (ABL 抑制剂) 透过 linker 与 LCL161 衍生物 (IAP 配体) 结合形成 SNIPER(ABL)-033，该结合物能有效促进 BCR-ABL 蛋白的降解，表现出 0.3 μM 的 DC50 值。