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LCL161 (1005342-46-0)

LCL161 is an oral small molecule antagonist of Inhibitor of Apoptosis Proteins (IAPs) that sensitizes a subset of tumors from diverse lineages to treatment with cytotoxic therapies…

Not Intended for Therapeutic Use. For research use only.

CAS: 1005342-46-0 Category

LCL161 (1005342-46-0) Description:

LCL161 is a n orally bioavailable second mitochondrial-derived activator of caspases (SMAC) mimetic and inhibitor of IAP (Inhibitor of Apoptosis Protein) family of proteins, with potential antineoplastic activity. SMAC mimetic LCL161 binds to IAPs, such as X chromosome-linked IAP (XIAP) and cellular IAPs 1 and 2. Since IAPs shield cancer cells from the apoptosis process, this agent may restore and promote the induction of apoptosis through apoptotic signaling pathways in cancer cells. IAPs are overexpressed by many cancer cell types and suppress apoptosis by binding and inhibiting active caspases-3, -7 and -9, which play essential roles in apoptosis (programmed cell death), necrosis and inflammation. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus). LCL161 is also a small molecule oral IAP antagonist in development for use in combination with cytotoxic agents. The effect of LCL161 on CYP3A4/5 (CYP3A) activity is investigated in vitro. Results in human liver microsomes indicated LCL161 inhibited CYP3A in a concentration- and time-dependent manner (KI of 0.797 µM and Kinact of 0.0803 min-1). LCL161 activates human PXR in a reporter gene assay and induced CYP3A4 mRNA up to ~5-fold in human hepatocytes.

LCL161 (1005342-46-0) Specifications:

Product Name LCL161
Synonym LCL161; LCL 161; LCL-161
Chemical Name (2S)-N-[(1S)-1-cyclohexyl-2-[(2S)-2-[4-(4-fluorobenzoyl)-1,3-thiazol-2-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propenamide, XIAP Inhibitor, IAP inhibitor
Drug Class Inhibitor
Purity ≥98% (HPLC)
CAS Number 1005342-46-0
Molecular Formula C26H33FN4O3S
Molecular Weight 500.63
Monoisotopic Mass 500.22574  g/mol
MDL number MFCD23160049
InChIKey UFPFGVNKHCLJJO-SSKFGXFMSA-N
InChi Code 1S/C26H33FN4O3S/c1-16(28-2)24(33)30-22(17-7-4-3-5-8-17)26(34)31-14-6-9-21(31)25-29-20(15-35-25)23(32)18-10-12-19(27)13-11-18/h10-13,15-17,21-22,28H,3-9,14H2,1-2H3,(H,30,33)/t16-,21-,22-/m0/s1
SMILES CC(C(=O)NC(C1CCCCC1)C(=O)N2CCCC2C3=NC(=CS3)C(=O)C4=CC=C(C=C4)F)NC
Form Powder
Color Yellow
Solubility  Soluble in Ethanol: 20 mg/ml warmed (39.94 mM); DMSO: 100 mg/ml (199.74 mM)
Storage Temp.  -20°C
Shelf life >5 years if stored properly
Handling Protect from air and light
Application An oral small molecule antagonist of Inhibitor of Apoptosis Proteins (IAPs)

 


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RIDADR NONH for all modes of transport

References:

[1]. Shekhar TM, Green MM, Rayner DM, Miles MA, Cutts SM, Hawkins CJ. Inhibition of Bcl-2 or IAP proteins does not provoke mutations in surviving cells. Mutat Res. 2015 Jul;777:23-32. doi: 10.1016/j.mrfmmm.2015.04.005. Epub 2015 Apr 15. PubMed PMID: 25916945.

[2]. Fulda S. Targeting inhibitor of apoptosis proteins for cancer therapy: a double-edge sword? J Clin Oncol. 2014 Oct 1;32(28):3190-1. doi: 10.1200/JCO.2014.56.8741. Epub 2014 Aug 11. PubMed PMID: 25113757.

[3]. Infante JR, Dees EC, Olszanski AJ, Dhuria SV, Sen S, Cameron S, Cohen RB. Phase I dose-escalation study of LCL161, an oral inhibitor of apoptosis proteins inhibitor, in patients with advanced solid tumors. J Clin Oncol. 2014 Oct 1;32(28):3103-10. doi: 10.1200/JCO.2013.52.3993. Epub 2014 Aug 11. PubMed PMID: 25113756.

[4]. Tian A, Wilson GS, Lie S, Wu G, Hu Z, Hebbard L, Duan W, George J, Qiao L. Synergistic effects of IAP inhibitor LCL161 and paclitaxel on hepatocellular carcinoma cells. Cancer Lett. 2014 Sep 1;351(2):232-41. doi: 10.1016/j.canlet.2014.06.006. Epub 2014 Jun 27. PubMed PMID: 24976294.

[5]. Faye MD, Beug ST, Graber TE, Earl N, Xiang X, Wild B, Langlois S, Michaud J, Cowan KN, Korneluk RG, Holcik M. IGF2BP1 controls cell death and drug resistance in rhabdomyosarcomas by regulating translation of cIAP1. Oncogene. 2015 Mar 19;34(12):1532-41. doi: 10.1038/onc.2014.90. Epub 2014 Apr 7. PubMed PMID: 24704827.