LBW242
WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#:406185
CAS#:867324-12-7
Description:LBW242 is a Smac mimetic, and potent IAP inhibitor. LBW242 is effective against mutant FLT3 at doses that are physiologically achievable and well tolerated in vivo. LBW242 also enhances the inhibitory effects of PKC412, as well as standard chemotherapeutic agents such as doxorubicin and Ara-c, by acting in an additive-synergistic fashion against mutant FLT3-expressing cells in vitro. LBW242 also sensitizes ovarian cancer cells to the antitumor effects of TRAIL and anticancer drugs commonly used in clinic.
Price and Availability
LBW242 is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.
Chemical Structure
Theoretical Analysis
MedKoo Cat#: 406185Name: LBW242CAS#: 867324-12-7Chemical Formula: C27H42N4O2Exact Mass: 454.33078Molecular Weight: 454.65Elemental Analysis: C, 71.33; H, 9.31; N, 12.32; O, 7.04
Synonym:LBW242; LBW 242; LBW-242.
IUPAC/Chemical Name:(S)-N-((S)-1-cyclohexyl-2-oxo-2-((3aR,7aS)-6-phenethyloctahydro-1H-pyrrolo[2,3-c]pyridin-1-yl)ethyl)-2-(methylamino)propanamide
InChi Key:HCSMRSHIIKPNAK-LSAVBLLPSA-N
InChi Code:InChI=1S/C27H42N4O2/c1-20(28-2)26(32)29-25(23-11-7-4-8-12-23)27(33)31-18-15-22-14-17-30(19-24(22)31)16-13-21-9-5-3-6-10-21/h3,5-6,9-10,20,22-25,28H,4,7-8,11-19H2,1-2H3,(H,29,32)/t20-,22+,24+,25-/m0/s1
SMILES Code:C[C@H](NC)C(N[C@@H](C1CCCCC1)C(N2CC[C@]3([H])[C@@]2([H])CN(CCC4=CC=CC=C4)CC3)=O)=O
Technical Data
References
1: Keating J, Tsoli M, Hallahan AR, Ingram WJ, HaberM, Ziegler DS. Targeting the inhibitor of apoptosis proteins as a noveltherapeutic strategy in medulloblastoma. Mol Cancer Ther. 2012Dec;11(12):2654-63. doi: 10.1158/1535-7163.MCT-12-0352. Epub 2012 Sep25. PubMed PMID: 23012247.
2: Petrucci E, Pasquini L, Bernabei M, Saulle E, Biffoni M, Accarpio F,Sibio S, Di Giorgio A, Di Donato V, Casorelli A, Benedetti-Panici P,Testa U. A small molecule SMAC mimic LBW242 potentiates TRAIL- andanticancer drug-mediated cell death of ovarian cancer cells. PLoS One.2012;7(4):e35073. doi: 10.1371/journal.pone.0035073. Epub 2012 Apr 25.PubMed PMID: 22558117; PubMed Central PMCID: PMC3338831.
3: Eschenburg G, Eggert A, Schramm A, Lode HN, Hundsdoerfer P. Smacmimetic LBW242 sensitizes XIAP-overexpressing neuroblastoma cells forTNF-α-independent apoptosis. Cancer Res. 2012 May 15;72(10):2645-56. doi:10.1158/0008-5472.CAN-11-4072. Epub 2012 Apr 9. PubMed PMID: 22491673.
4: Ziegler DS, Keating J, Kesari S, Fast EM, Zawel L, Ramakrishna N,Barnes J, Kieran MW, Veldhuijzen van Zanten SE, Kung AL. Asmall-molecule IAP inhibitor overcomes resistance to cytotoxic therapiesin malignant gliomas in vitro and in vivo. Neuro Oncol. 2011Aug;13(8):820-9. doi: 10.1093/neuonc/nor066. Epub 2011 Jul 1. PubMedPMID: 21724651; PubMed Central PMCID: PMC3145470.
5: Xu Y, Zhou L, Huang J, Liu F, Yu J, Zhan Q, Zhang L, Zhao X. Role ofSmac in determining the chemotherapeutic response of esophageal squamouscell carcinoma. Clin Cancer Res. 2011 Aug 15;17(16):5412-22. doi:10.1158/1078-0432.CCR-11-0426. Epub 2011 Jun 15. PubMed PMID: 21676925.
6: Hundsdoerfer P, Dietrich I, Schmelz K, Eckert C, Henze G. XIAPexpression is post-transcriptionally upregulated in childhood ALL and isassociated with glucocorticoid response in T-cell ALL. Pediatr BloodCancer. 2010 Aug;55(2):260-6. doi: 10.1002/pbc.22541. PubMed PMID:20582956.
7: Weber A, Kirejczyk Z, Besch R, Potthoff S, Leverkus M, Häcker G.Proapoptotic signalling through Toll-like receptor-3 involvesTRIF-dependent activation of caspase-8 and is under the control ofinhibitor of apoptosis proteins in melanoma cells. Cell Death Differ.2010 Jun;17(6):942-51. doi: 10.1038/cdd.2009.190. Epub 2009 Dec 18.PubMed PMID: 20019748.
8: Ziegler DS, Wright RD, Kesari S, Lemieux ME, Tran MA, Jain M, ZawelL, Kung AL. Resistance of human glioblastoma multiforme cells to growthfactor inhibitors is overcome by blockade of inhibitor of apoptosisproteins. J Clin Invest. 2008 Sep;118(9):3109-22. doi: 10.1172/JCI34120.PubMed PMID: 18677408; PubMed Central PMCID: PMC2491457.
9: Gaither A, Porter D, Yao Y, Borawski J, Yang G, Donovan J, Sage D,Slisz J, Tran M, Straub C, Ramsey T, Iourgenko V, Huang A, Chen Y,Schlegel R, Labow M, Fawell S, Sellers WR, Zawel L. A Smac mimeticrescue screen reveals roles for inhibitor of apoptosis proteins in tumornecrosis factor-alpha signaling. Cancer Res. 2007 Dec 15;67(24):11493-8.PubMed PMID: 18089776.
10: Weisberg E, Kung AL, Wright RD, Moreno D, Catley L, Ray A, Zawel L,Tran M, Cools J, Gilliland G, Mitsiades C, McMillin DW, Jiang J,Hall-Meyers E, Griffin JD. Potentiation of antileukemic therapies bySmac mimetic, LBW242: effects on mutant FLT3-expressing cells. MolCancer Ther. 2007 Jul;6(7):1951-61. PubMed PMID: 17620426.
11: Chauhan D, Neri P, Velankar M, Podar K, Hideshima T, Fulciniti M,Tassone P, Raje N, Mitsiades C, Mitsiades N, Richardson P, Zawel L, TranM, Munshi N, Anderson KC. Targeting mitochondrial factor Smac/DIABLO astherapy for multiple myeloma (MM). Blood. 2007 Feb 1;109(3):1220-7. Epub2006 Oct 10. PubMed PMID: 17032924; PubMed Central PMCID: PMC1785138.
