Dactolisib tosylate
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MedKoo CAT#: 581211

CAS#: 1028385-32-1 (tosylate)

Description: Dactolisib tosylate is also known as NVP-BEZ 235 Tosylate. NVP-BEZ235 is an imidazo[4,5-c]quinoline derivative that inhibits PI3K and mTOR kinase activity by binding to the ATP-binding cleft of these enzymes. The IC50s for PI3Kα, β, γ, δ are 4, 75, 7, 5 nM, respectively. It is also found to be as active against the mutant PI3KαE545K or PI3KαH1047R with IC50s of 5.7 and 4.6 nM, respectively. In human tumor cell lines, it is able to effectively and specifically block the dysfunctional activation of the PI3K pathway, inducing G1 arrest. PTEN-null cell lines PC3M and U87MG shows a dose-dependent reduction in cell proliferation when treated with increasing concentrations of NVP-BEZ235, with an average GI50 of 10 to 12 nM. In Vivo NVP-BEZ235 is well tolerated, displays disease stasis when administered orally, and enhances the efficacy of other anticancer agents. At a dose of 50 mg/kg, NVP-BEZ235 appears rapidly in plasma with a Cmax of 1.68 μM at 0.5 h and a C24h of 0.03 μM.

Chemical Structure

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Dactolisib tosylate
CAS# 1028385-32-1 (tosylate)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 581211
Name: Dactolisib tosylate
CAS#: 1028385-32-1 (tosylate)
Chemical Formula: C37H31N5O4S
Exact Mass: 641.21
Molecular Weight: 641.750
Elemental Analysis: C, 69.25; H, 4.87; N, 10.91; O, 9.97; S, 5.00

Price and Availability

Size Price Availability Quantity
100mg USD 350 2 weeks
200mg USD 600 2 weeks
500mg USD 1250 2 weeks
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Related CAS #: 1028385-32-1 (tosylate)   915019-65-7 (free base)   2319647-83-9 (HCl)  

Synonym: Dactolisib tosylate; NVP-BEZ235-ANA; UNII-U54GT9151S; BEZ235 Tosylate; NVP-BEZ 235 Tosylate;

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)propanenitrile 4-methylbenzenesulfonate

InChi Key: FWURTHAUPVXZHW-UHFFFAOYSA-N

InChi Code: InChI=1S/C30H23N5O.C7H8O3S/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;1-6-2-4-7(5-3-6)11(8,9)10/h4-17H,1-3H3;2-5H,1H3,(H,8,9,10)

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.O=S(C7=CC=C(C)C=C7)(O)=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Product Data:
Product Data
Instruction:
View handling instruction
Biological target: Dactolisib Tosylate (BEZ235 Tosylate) is a dual PI3K and mTOR kinase inhibitor with IC50 values of 4, 75, 7, 5 nM for PI3Kα, β, γ, δ, respectively.
In vitro activity: BEZ235 reduced cell viability in a dose-dependent manner, as shown by CCK8 assays (Figure 1A). The IC50 values of BEZ235 for HL-60/VCR and K562/ADR cells were 66.69 nmol/L and 71.44 nmol/L, respectively. After treatment with different concentrations of BEZ235 for 24 h, the migration of both cell lines significantly decreased (Figure 1B). BEZ235 also induced apoptosis in the HL60/VCR and K562/ADR cells in a dose-dependent manner (Figure 1C). Reference: Acta Pharmacol Sin. 2017 Mar; 38(3): 382–391. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342661/
In vivo activity: Subsequently, the peeled tumors were subjected to paraffin embedded sections. The protein expressions of p53 and p21 in tumor sections were tested by IHC assays. In both K1 and C643 tumors, p21 expression was higher in NVP-BEZ235 treated mice compared with the controls, since an increased percent and stronger staining of p21 positive cells were observed. While only the mice bearing K1 tumors displayed greater portion and stronger staining of p53 positive cells, rather than C643 tumors. These results suggested a p53-independent mechanism of p21 up-regulation in NVP-BEZ235 treated C643 xenograft tumors, which was consistent with the results of in-vitro studies. Moreover, the mitotic cell marker, Ki67 was shown much weaker in the NVP-BEZ235 treated tumors than the control tumors, further suggested NVP-BEZ235 suppresses thyroid cancer cell proliferation (Figure 7C). Taken together, these results indicated that NVP-BEZ235 treatment inhibited tumor growth in mice injected with K1 cells or C643 cells and substantiate our findings that NVP-BEZ235 inhibits thyroid cancer growth independent of TP53 status. Reference: Int J Biol Sci. 2020; 16(4): 682–693. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990918/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 34.0 52.98

Preparing Stock Solutions

The following data is based on the product molecular weight 641.75 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Cai J, Xia J, Zou J, Wang Q, Ma Q, Sun R, Liao H, Xu L, Wang D, Guo X. The PI3K/mTOR dual inhibitor NVP-BEZ235 stimulates mutant p53 degradation to exert anti-tumor effects on triple-negative breast cancer cells. FEBS Open Bio. 2020 Apr;10(4):535-545. doi: 10.1002/2211-5463.12806. Epub 2020 Mar 6. PMID: 32027103; PMCID: PMC7137801. 2. Deng L, Jiang L, Lin XH, Tseng KF, Liu Y, Zhang X, Dong RH, Lu ZG, Wang XJ. The PI3K/mTOR dual inhibitor BEZ235 suppresses proliferation and migration and reverses multidrug resistance in acute myeloid leukemia. Acta Pharmacol Sin. 2017 Mar;38(3):382-391. doi: 10.1038/aps.2016.121. Epub 2017 Jan 2. PMID: 28042875; PMCID: PMC5342661. 3. Ruan B, Liu W, Chen P, Cui R, Li Y, Ji M, Hou P, Yang Q. NVP-BEZ235 inhibits thyroid cancer growth by p53- dependent/independent p21 upregulation. Int J Biol Sci. 2020 Jan 14;16(4):682-693. doi: 10.7150/ijbs.37592. PMID: 32025215; PMCID: PMC6990918 4. Shi F, Zhang J, Liu H, Wu L, Jiang H, Wu Q, Liu T, Lou M, Wu H. The dual PI3K/mTOR inhibitor dactolisib elicits anti-tumor activity in vitro and in vivo. Oncotarget. 2017 Dec 9;9(1):706-717. doi: 10.18632/oncotarget.23091. Erratum in: Oncotarget. 2018 Mar 30;9(24):17255. PMID: 29416647; PMCID: PMC5787502.
In vitro protocol: 1. Cai J, Xia J, Zou J, Wang Q, Ma Q, Sun R, Liao H, Xu L, Wang D, Guo X. The PI3K/mTOR dual inhibitor NVP-BEZ235 stimulates mutant p53 degradation to exert anti-tumor effects on triple-negative breast cancer cells. FEBS Open Bio. 2020 Apr;10(4):535-545. doi: 10.1002/2211-5463.12806. Epub 2020 Mar 6. PMID: 32027103; PMCID: PMC7137801. 2. Deng L, Jiang L, Lin XH, Tseng KF, Liu Y, Zhang X, Dong RH, Lu ZG, Wang XJ. The PI3K/mTOR dual inhibitor BEZ235 suppresses proliferation and migration and reverses multidrug resistance in acute myeloid leukemia. Acta Pharmacol Sin. 2017 Mar;38(3):382-391. doi: 10.1038/aps.2016.121. Epub 2017 Jan 2. PMID: 28042875; PMCID: PMC5342661.
In vivo protocol: 1. Shi F, Zhang J, Liu H, Wu L, Jiang H, Wu Q, Liu T, Lou M, Wu H. The dual PI3K/mTOR inhibitor dactolisib elicits anti-tumor activity in vitro and in vivo. Oncotarget. 2017 Dec 9;9(1):706-717. doi: 10.18632/oncotarget.23091. Erratum in: Oncotarget. 2018 Mar 30;9(24):17255. PMID: 29416647; PMCID: PMC5787502. 2. Ruan B, Liu W, Chen P, Cui R, Li Y, Ji M, Hou P, Yang Q. NVP-BEZ235 inhibits thyroid cancer growth by p53- dependent/independent p21 upregulation. Int J Biol Sci. 2020 Jan 14;16(4):682-693. doi: 10.7150/ijbs.37592. PMID: 32025215; PMCID: PMC6990918.

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1: Witteck L, Jaster R. Trametinib and dactolisib but not regorafenib exert antiproliferative effects on rat pancreatic stellate cells. Hepatobiliary Pancreat Dis Int. 2015 Dec;14(6):642-50. PubMed PMID: 26663013.

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