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LCL161 CAS: 1005342-46-0

Category: Inhibitors
Product Name: LCL161
Cat No: I000089
CAS No: 1005342-46-0
Synonyms: LCL161; LCL 161; LCL-161
Molecular Formula: C26H33FN4O3S
Molecular Weight: 500.6
SMILES: O=C(N1CCC[C@H]1C2=NC(C(C3=CC=C(F)C=C3)=O)=CS2)[C@@H](NC([C@@H](NC)C)=O)C4CCCCC4
InChI: None
InChIKey: UFPFGVNKHCLJJO-SSKFGXFMSA-N
Solubility: 10 mM in DMSO
Target: IAP
Storage: Store at -20°C
CAS 1005342-46-0,LCL161
  • Description

LCL161 is an orally bioavailable SMAC mimetic and inhibitor of Inhibitor of Apoptosis Protein (IAP) family of proteins, with antineoplastic activity. 

in vitro: Huh-7 cells co-treated with LCL161 and SC-2001 showed a significant dose-dependent apoptotic effect demonstrated by sub-G1 assay and cleavage of PARP. Furthermore, the combination index (CI) ofLCL161 and SC-2001 showed a convincing synergism in resistant Huh-7. Results in human liver microsomes indicated LCL161 inhibited CYP3A in a concentration- and time-dependent manner (KI of 0.797 uM and kinact of 0.0803 min(-1) ). LCL161 activated human PXR in a reporter gene assay and induced CYP3A4 mRNA up to 5-fold in human hepatocytes. LCL161 caused rapid degradation of cIAP1 leading to TNFα secretion, LCL161 did not promote apoptosis significantly. However, LCL161 induced expression of MICA and MICB, ligands for the activating immune receptor NKG2D, and enhanced the susceptibility of HL cells to NKG2D-dependent lysis by NK cells

in vivo: The combinational therapy showed significant growth inhibition in Huh-7-bearing xenograft tumors. Notably, down regulation of Bcl-2 was observed in a tumor sample treated with LCL161 and SC-2001

Clinical trial: Phase I Trial of LCL-161 and Gemcitabine Plus Nab-Paclitaxel in Metastatic Pancreatic Cancer. Phase 1

  • Spec

Appearance:Solid powder
Purity: > 98%

  • References


1:LCL161 increases paclitaxel-induced apoptosis by degrading cIAP1 and cIAP2 in NSCLC. Yang C, Wang H, Zhang B, Chen Y, Zhang Y, Sun X, Xiao G, Nan K, Ren H, Qin S.J Exp Clin Cancer Res. 2016 Sep 30;35(1):158. PMID: 27737687 Free PMC Article
2:Smac mimetic LCL161 supports neuroblastoma chemotherapy in a drug class-dependent manner and synergistically interacts with ALK inhibitor TAE684 in cells with ALK mutation F1174L. Najem S, Langemann D, Appl B, Trochimiuk M, Hundsdoerfer P, Reinshagen K, Eschenburg G.Oncotarget. 2016 Nov 8;7(45):72634-72653. doi: 10.18632/oncotarget.12055. PMID: 27655666 Free PMC Article
3:[Effects of LCL161, a Smac mimetic on the proliferation and apoptosis in hepatocellular carcinoma cells]. Ren K, Ma L, Chong D, Zhang Z, Zhou C, Liu H, Zhao S.Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2016 Sep 28;41(9):898-904. doi: 10.11817/j.issn.1672-7347.2016.09.003. Chinese. PMID: 27640787 Free Article
4:Smac mimetic LCL161 overcomes protective ER stress induced by obatoclax, synergistically causing cell death in multiple myeloma. Ramakrishnan V, Gomez M, Prasad V, Kimlinger T, Painuly U, Mukhopadhyay B, Haug J, Bi L, Rajkumar SV, Kumar S.Oncotarget. 2016 Aug 30;7(35):56253-56265. doi: 10.18632/oncotarget.11028. PMID: 27494845 Free PMC Article
5:Cytotoxic effects of SMAC-mimetic compound LCL161 in head and neck cancer cell lines. Brands RC, Herbst F, Hartmann S, Seher A, Linz C, Kübler AC, Müller-Richter UD.Clin Oral Investig. 2016 Dec;20(9):2325-2332. Epub 2016 Feb 4. PMID: 26846923
6:Sensitization of acute lymphoblastic leukemia cells for LCL161-induced cell death by targeting redox homeostasis. Haß C, Belz K, Schoeneberger H, Fulda S.Biochem Pharmacol. 2016 Apr 1;105:14-22. doi: 10.1016/j.bcp.2016.01.004. Epub 2016 Jan 13. PMID: 26774450
7:Phase I dose-escalation study of LCL161, an oral inhibitor of apoptosis proteins inhibitor, in patients with advanced solid tumors. Infante JR, Dees EC, Olszanski AJ, Dhuria SV, Sen S, Cameron S, Cohen RB.J Clin Oncol. 2014 Oct 1;32(28):3103-10. doi: 10.1200/JCO.2013.52.3993. Epub 2014 Aug 11. PMID: 25113756
8:Synergistic effects of IAP inhibitor LCL161 and paclitaxel on hepatocellular carcinoma cells. Tian A, Wilson GS, Lie S, Wu G, Hu Z, Hebbard L, Duan W, George J, Qiao L.Cancer Lett. 2014 Sep 1;351(2):232-41. doi: 10.1016/j.canlet.2014.06.006. Epub 2014 Jun 27. PMID: 24976294
9:Smac mimetic compound LCL161 sensitizes esophageal carcinoma cells to radiotherapy by inhibiting the expression of inhibitor of apoptosis protein. Qin Q, Zuo Y, Yang X, Lu J, Zhan L, Xu L, Zhang C, Zhu H, Liu J, Liu Z, Tao G, Dai S, Zhang X, Ma J, Cai J, Sun X.Tumour Biol. 2014 Mar;35(3):2565-74. doi: 10.1007/s13277-013-1338-2. Epub 2013 Oct 30. PMID: 24170321
10:Time-dependent inhibition and induction of human cytochrome P4503A4/5 by an oral IAP antagonist, LCL161, in vitro and in vivo in healthy subjects. Dhuria S, Einolf H, Mangold J, Sen S, Gu H, Wang L, Cameron S.J Clin Pharmacol. 2013 Jun;53(6):642-53. doi: 10.1002/jcph.79. Epub 2013 Apr 15. PMID: 23585187


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