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MedKoo CAT#: 200491
CAS#: 915019-65-7 (free base)
Description: Dactolisib, also known as BEZ235, is an orally bioavailable phosphatidylinositol 3-kinase (PI3K) inhibitor with potential antineoplastic activity. PI3K inhibitor BEZ235 specifically inhibits PIK3 in the PI3K/AKT kinase (or protein kinase B) signaling pathway, which may trigger the translocation of cytosolic Bax to the mitochondrial outer membrane, increasing mitochondrial membrane permeability; apoptotic cell death may ensue. Bax is a member of the proapoptotic Bcl2 family of proteins.
MedKoo Cat#: 200491
Name: Dactolisib
CAS#: 915019-65-7 (free base)
Chemical Formula: C30H23N5O
Exact Mass: 469.19026
Molecular Weight: 469.54
Elemental Analysis: C, 76.74; H, 4.94; N, 14.92; O, 3.41
Related CAS #: 1028385-32-1 (tosylate) 915019-65-7 (free base)
Synonym: BEZ235; BEZ-235; BEZ 235; NVPBEZ235; NVP-BEZ235; NVP-BEZ-235; NVP-BEZ 235; Dactolisib.
IUPAC/Chemical Name: 2-Methyl-2-[4-[3-methyl-2-oxo-8-(quinolin-3-yl)-2,3-dihydroimidazo[4,5-c]quinolin-1-yl]phenyl]propionitrile.
InChi Key: JOGKUKXHTYWRGZ-UHFFFAOYSA-N
InChi Code: InChI=1S/C30H23N5O/c1-30(2,18-31)22-9-11-23(12-10-22)35-28-24-15-19(21-14-20-6-4-5-7-25(20)32-16-21)8-13-26(24)33-17-27(28)34(3)29(35)36/h4-17H,1-3H3
SMILES Code: CC(C1=CC=C(N(C2=C3C=NC4=CC=C(C5=CC6=CC=CC=C6N=C5)C=C24)C(N3C)=O)C=C1)(C)C#N
BEZ235 is a dual phosphatidylinositol 3-kinase (PI(3)K)/mammalian target of rapamycin (mTOR) inhibitor that is orally available and that has been shown to be effective in several malignancies in vitro. Recently, BEZ235 entered clinical trials for solid tumors.
1: Passacantilli I, Capurso G, Archibugi L, Calabretta S, Caldarola S, Loreni F, Delle Fave G, Sette C. Combined therapy with RAD001 e BEZ235 overcomes resistance of PET immortalized cell lines to mTOR inhibition. Oncotarget. 2014 Jul 30;5(14):5381-91. PubMed PMID: 25026292.
2: Park HS, Hong SK, Oh MM, Yoon CY, Jeong SJ, Byun SS, Cheon J, Lee SE, Moon du G. Synergistic antitumor effect of NVP-BEZ235 and sunitinib on docetaxel-resistant human castration-resistant prostate cancer cells. Anticancer Res. 2014 Jul;34(7):3457-68. PubMed PMID: 24982354.
3: Moon du G, Lee SE, Oh MM, Lee SC, Jeong SJ, Hong SK, Yoon CY, Byun SS, Park HS, Cheon J. NVP-BEZ235, a dual PI3K/mTOR inhibitor synergistically potentiates the antitumor effects of cisplatin in bladder cancer cells. Int J Oncol. 2014 Sep;45(3):1027-35. doi: 10.3892/ijo.2014.2505. Epub 2014 Jun 19. PubMed PMID: 24969552; PubMed Central PMCID: PMC4121414.
4: Qu Y, Wu X, Yin Y, Yang Y, Ma D, Li H. Antitumor activity of selective MEK1/2 inhibitor AZD6244 in combination with PI3K/mTOR inhibitor BEZ235 in gefitinib-resistant NSCLC xenograft models. J Exp Clin Cancer Res. 2014 Jun 17;33:52. doi: 10.1186/1756-9966-33-52. PubMed PMID: 24939055; PubMed Central PMCID: PMC4074836.
5: Oishi T, Itamochi H, Kudoh A, Nonaka M, Kato M, Nishimura M, Oumi N, Sato S, Naniwa J, Sato S, Shimada M, Kigawa J, Harada T. The PI3K/mTOR dual inhibitor NVP-BEZ235 reduces the growth of ovarian clear cell carcinoma. Oncol Rep. 2014 Aug;32(2):553-8. doi: 10.3892/or.2014.3268. Epub 2014 Jun 13. PubMed PMID: 24927217.
6: Seixas JD, Luengo-Arratta SA, Diaz R, Saldivia M, Rojas-Barros DI, Manzano P, Gonzalez S, Berlanga M, Smith TK, Navarro M, Pollastri MP. Establishment of a structure-activity relationship of 1H-imidazo[4,5-c]quinoline-based kinase inhibitor NVP-BEZ235 as a lead for African sleeping sickness. J Med Chem. 2014 Jun 12;57(11):4834-48. doi: 10.1021/jm500361r. Epub 2014 May 21. PubMed PMID: 24805946; PubMed Central PMCID: PMC4099174.
7: Seo BR, Min KJ, Cho IJ, Kim SC, Kwon TK. Curcumin significantly enhances dual PI3K/Akt and mTOR inhibitor NVP-BEZ235-induced apoptosis in human renal carcinoma Caki cells through down-regulation of p53-dependent Bcl-2 expression and inhibition of Mcl-1 protein stability. PLoS One. 2014 Apr 17;9(4):e95588. doi: 10.1371/journal.pone.0095588. eCollection 2014. PubMed PMID: 24743574; PubMed Central PMCID: PMC3990719.
8: Kuger S, Cörek E, Polat B, Kämmerer U, Flentje M, Djuzenova CS. Novel PI3K and mTOR Inhibitor NVP-BEZ235 Radiosensitizes Breast Cancer Cell Lines under Normoxic and Hypoxic Conditions. Breast Cancer (Auckl). 2014 Mar 16;8:39-49. doi: 10.4137/BCBCR.S13693. eCollection 2014. PubMed PMID: 24678241; PubMed Central PMCID: PMC3964191.
9: Hong SW, Shin JS, Moon JH, Kim YS, Lee J, Choi EK, Ha SH, Lee DH, Chung HN, Kim JE, Kim KP, Hong YS, Lee JL, Lee WJ, Choi EK, Lee JS, Jin DH, Kim TW. NVP-BEZ235, a dual PI3K/mTOR inhibitor, induces cell death through alternate routes in prostate cancer cells depending on the PTEN genotype. Apoptosis. 2014 May;19(5):895-904. doi: 10.1007/s10495-014-0973-4. PubMed PMID: 24652480.
10: Jebahi A, Villedieu M, Pétigny-Lechartier C, Brotin E, Louis MH, Abeilard E, Giffard F, Guercio M, Briand M, Gauduchon P, Lheureux S, Poulain L. PI3K/mTOR dual inhibitor NVP-BEZ235 decreases Mcl-1 expression and sensitizes ovarian carcinoma cells to Bcl-xL-targeting strategies, provided that Bim expression is induced. Cancer Lett. 2014 Jun 28;348(1-2):38-49. doi: 10.1016/j.canlet.2014.03.001. Epub 2014 Mar 18. PubMed PMID: 24650799.
