dactolisib

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| ImageFile = Dactolisib.svg

| ImageSize = 220px

| ImageFile1 = Dactolisib molecule ball.png

| ImageSize1 = 240

| ImageAlt1 = Ball-and-stick model of the BEZ235 molecule

| PIN = 2-Methyl-2-{4-[3-methyl-2-oxo-8-(quinolin-3-yl)-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl]phenyl}propanenitrile

| OtherNames = NVP-BEZ235; BEZ-235; RTB101

| Section1 = {{Chembox Identifiers

| IUPHAR_ligand = 7950

| CASNo = 915019-65-7

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| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = RUJ6Z9Y0DT

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| StdInChI = 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

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = JOGKUKXHTYWRGZ-UHFFFAOYSA-N

| PubChem = 11977753

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 1879463

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| ChemSpiderID = 10151099

| SMILES = N#CC(c6ccc(N5c4c(cnc3ccc(c1cc2ccccc2nc1)cc34)N(C5=O)C)cc6)(C)C

| KEGG = D10552

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| Section2 = {{Chembox Properties

| C=30 | H=23 | N=5 | O=1

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Dactolisib (codenamed NVP-BEZ235 and BEZ-235, also known as RTB101) is an imidazoquinoline derivative acting as a PI3K inhibitor.{{cite journal | last1 = Liu | first1 = TJ | last2 = Koul | first2 = D | last3 = LaFortune | first3 = T | last4 = Tiao | first4 = N | last5 = Shen | first5 = RJ | last6 = Maira | first6 = SM | last7 = Garcia-Echevrria | first7 = C | last8 = Yung | first8 = WKA | title = NVP-BEZ235, a Novel Dual Phosphatidylinositol 3-kinase/Mammalian Target of Rapamycin Inhibitor, Elicits Multifaceted Antitumor Activities in Human Gliomas | journal = Molecular Cancer Therapeutics | date = 11 August 2009 | volume = 8 | issue = 8 | pages = 2204–10 | doi = 10.1158/1535-7163.MCT-09-0160 | pmid = 19671762 | pmc = 2752877}} It also inhibits mTOR.{{cite journal | last1 = Awasthi | first1 = N | last2 = Yen | first2 = PL | last3 = Schwarz | first3 = MA | last4 = Schwarz | first4 = RE | title = The Efficacy of a Novel, Dual PI3K/mTOR Inhibitor NVP-BEZ235 to Enhance Chemotherapy and Antiangiogenic Response in Pancreatic Cancer | journal = Journal of Cellular Biochemistry | date = March 2012 | volume = 113 | issue = 3 | pages = 784–91 | doi = 10.1002/jcb.23405 | pmid = 22020918 | s2cid = 23005922 }} It is being investigated as a possible cancer treatment.{{cite journal | last1 = Maira | first1 = SM | last2 = Stauffer | first2 = F | last3 = Schnell | first3 = C | last4 = García-Echeverría | first4 = C | title = PI3K Inhibitors for Cancer Treatment: Where Do We Stand? | journal = Biochemical Society Transactions | date = 1 February 2009 | volume = 37 | issue = 1 | pages = 265–72 | doi = 10.1042/BST0370265 | pmid=19143644}}

It has been shown to be toxic to Waldenström's macroglobulinemia cells.{{cite journal | last1 = Sacco | first1 = A | last2 = Roccaro | first2 = A | last3 = Ghobrial | first3 = IM | title = Role of Dual PI3/Akt and mTOR Inhibition in Waldenström's Macroglobulinemia | journal = Oncotarget | date = November 2010 | volume = 1 | issue = 7 | pages = 578–82 | doi = 10.18632/oncotarget.192| pmid = 21317453 | pmc = 3248138}}

It was the first PI3K inhibitor to enter clinical trials, in 2006.{{cite web | title = A Phase I/II Study of BEZ235 in Patients with Advanced Solid Malignancies Enriched by Patients with Advanced Breast Cancer | url = http://clinicaltrials.gov/ct2/show/NCT00620594 | publisher = ClinicalTrials.gov | access-date = 16 July 2016}}

A phase IB/II clinical trial for locally advanced or metastatic HER2 negative breast cancer has completed.[https://clinicaltrials.gov/ct2/show/NCT01495247 Phase Ib/II Trial of BEZ235 With Paclitaxel in Patients With HER2 Negative, Locally Advanced or Metastatic Breast Cancer]

A phase II clinical trial for advanced pancreatic neuroendocrine tumors (pNET) had initially reported results, but was later terminated because insufficient normal tissue tolerance to the drug.[https://clinicaltrials.gov/ct2/show/results/NCT01658436 BEZ235 Phase II Trial in Patients With Advanced Pancreatic Neuroendocrine Tumors (pNET) After Failure of mTOR Inhibitor Therapy.]

A phase I clinical trial of BEZ235 in patients with advanced renal cell carcinoma had to be terminated prematurely due to toxicity and a lack of clinical efficacy .{{cite journal | title = BEZ235: When Promising Science Meets Clinical Reality | year = 2016 | journal = The Oncologist | pmc = 5016067 | last1 = Pongas | first1 = G. | last2 = Fojo | first2 = T. | volume = 21 | issue = 9 | pages = 1033–1034 | doi = 10.1634/theoncologist.2016-0243 | pmid = 27566248 }}

Another Phase Ib study on patients with various solid cancers found severe normal tissue toxicity as well when BEZ235/Dactolisib was administered in combination with the mTOR inhibitor Everolimus. The authors concluded that the combination of both drugs demonstrated limited efficacy and tolerance. BEZ235 systemic exposure increased in a dose-proportional manner while oral bioavailability was quite low, which may be related to gastrointestinal-specific toxicity .{{cite web | title = A Phase Ib Study of the Dual PI3K/mTOR Inhibitor Dactolisib(BEZ235) Combined with Everolimus in Patients with AdvancedSolid Malignancies | url = https://core.ac.uk/reader/81180444 | publisher = Target Oncology | access-date = 29 March 2017}}

A phase I study of BEZ-235 to treat acute lymphoid leukaemia was initiated in 2012, but no results were published since then.{{cite web | title = A Phase I, Dose-finding Study of BEZ235 in Adult Patients With Relapsed or Refractory Acute Leukemia | url = https://clinicaltrials.gov/ct2/show/NCT01756118 | publisher = clinicatrials.gov | access-date = 29 July 2020}}

A phase 2a randomized, placebo-controlled clinical trial published in 2018 showed that everolimus in combination with dactolisib decreased the rate of reported infections in an elderly population.{{cite journal | author=Zhavoronkov A | author-link=Alex Zhavoronkov | title=Geroprotective and senoremediative strategies to reduce the comorbidity, infection rates, severity, and lethality in gerophilic and gerolavic infections | journal=Aging | volume=12 | issue=8 | pages=6492–6510 | year=2020 | doi =10.18632/aging.102988 | pmc=7202545 | pmid=32229705}}