AT7519 trifluoroacetate | CAS#1431697-85-6 | CDK inhibitor

MedKoo Cat#: 462404 | Name: AT7519 trifluoroacetate

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

AT7519 trifluoroacetate is a potent inhibitor of CDKs.

Chemical Structure

AT7519 trifluoroacetate

CAS#1431697-85-6 (trifluoroacetate)

Theoretical Analysis

MedKoo Cat#: 462404

Name: AT7519 trifluoroacetate

CAS#: 1431697-85-6 (trifluoroacetate)

Chemical Formula: C18H18Cl2F3N5O4

Exact Mass: 0.0000

Molecular Weight: 496.27

Elemental Analysis: C, 43.56; H, 3.66; Cl, 14.29; F, 11.48; N, 14.11; O, 12.90

Price and Availability

Size	Price	Availability
10mg	USD 300.00	2 Weeks
50mg	USD 650.00	2 Weeks
100mg	USD 950.00	2 Weeks

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Related CAS #

902135-91-5 (HCl) 844442-38-2 (free base) 902135-89-1(methanesulfonate) 1431697-85-6 (trifluoroacetate)

Synonym

AT7519 trifluoroacetate; AT 7519 trifluoroacetate; AT-7519 trifluoroacetate

IUPAC/Chemical Name

4-(2,6-dichlorobenzamido)-N-(piperidin-4-yl)-1H-pyrazole-3-carboxamide 2,2,2-trifluoroacetate

InChi Key

XTOQTRBZWZONHQ-UHFFFAOYSA-N

InChi Code

InChI=1S/C16H17Cl2N5O2.C2HF3O2/c17-10-2-1-3-11(18)13(10)15(24)22-12-8-20-23-14(12)16(25)21-9-4-6-19-7-5-9;3-2(4,5)1(6)7/h1-3,8-9,19H,4-7H2,(H,20,23)(H,21,25)(H,22,24);(H,6,7)

SMILES Code

O=C(C1=C(C=CC=C1Cl)Cl)NC2=CNN=C2C(NC3CCNCC3)=O.O=C(C(F)(F)F)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

>3 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:

AT7519 trifluoroacetate is a potent inhibitor of CDKs, with IC50s of 210, 47, 100, 13, 170, and <10 nM for CDK1, CDK2, CDK4 to CDK6, and CDK9, respectively.

In vitro activity:

To investigate whether AT7519-induced cytotoxic effects were plausibly due to the apoptosis induction, the binding of annexin-V in combination with PI was analyzed by flow cytometry method. Intriguingly, FACS analysis of annexin-V/PI demonstrated that the inhibition of CDK increased the proportion of both early and late apoptotic cells, which was in agreement with the elevated sub-G1. As presented in Figure 4, AT7519 considerably increased annexin-V-positive NB4 cells from 10.8% in 100 nM to 35.8% in 500 nM of the inhibitor and also enhanced annexin-V/PI double-positive cell from 13.5% to 53.6% in 100 and 500 nM of the inhibitor, respectively. Taken together, these results showed that the inhibition of CDK using AT7519 halted NB4 cell progression, at least partly, through the induction of apoptotic pathway. Reference: Iran J Pharm Res. 2020 Summer; 19(3): 144–155. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758003/

In vivo activity:

Mice were treated daily with i.p. injections of 5, 10 or 15 mg/kg AT7519 in a 5-days on, 2-days off schedule for three weeks consecutively. AT7519 inhibited the growth of AMC711T neuroblastoma xenografts in a dose-dependent manner, with even the lowest dose of 5 mg/kg providing a statistically significant reduction in tumour growth (Fig. 3A and Supplementary Fig. S5A). Treatment with either 10 or 15 mg/kg AT7519 almost completely blocked tumour growth, resulting in a significantly improved anticancer effect compared with 5 mg/kg AT7519 (Fig. 3A). More rapid tumour growth was observed after terminating treatment with AT7519 (Supplementary Fig. S5B). This study also tested AT7519 (15 mg/kg) in MYCN-amplified KCNR neuroblastoma xenografts and found a 50% reduction in tumour growth compared to saline control at day 17 after treatment initiation (Supplementary Fig. S5C). Reference: Clin Cancer Res. 2015 Nov 15; 21(22): 5100–5109. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4645454/

Preparing Stock Solutions

The following data is based on the product molecular weight 496.27 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.

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. Pourbagheri-Sigaroodi A, Safaroghli-Azar A, Shanaki M, Yousefi AM, Anjam Najmedini A, Bashash D. Inhibition of Cyclin-dependent Kinase (CDK) Decreased Survival of NB4 Leukemic Cells: Proposing a p53-Independent Sensitivity of Leukemic Cells to Multi-CDKs Inhibitor AT7519. Iran J Pharm Res. 2020 Summer;19(3):144-155. doi: 10.22037/ijpr.2020.113170.14148. PMID: 33680018; PMCID: PMC7758003. 2. Zabihi M, Safaroghli-Azar A, Gharehbaghian A, Allahbakhshian Farsani M, Bashash D. CDK Blockade Using AT7519 Suppresses Acute Myeloid Leukemia Cell Survival through the Inhibition of Autophagy and Intensifies the Anti-leukemic Effect of Arsenic Trioxide. Iran J Pharm Res. 2019 Fall;18(Suppl1):119-131. doi: 10.22037/ijpr.2019.112560.13827. PMID: 32802093; PMCID: PMC7393062. 3. Dolman ME, Poon E, Ebus ME, den Hartog IJ, van Noesel CJ, Jamin Y, Hallsworth A, Robinson SP, Petrie K, Sparidans RW, Kok RJ, Versteeg R, Caron HN, Chesler L, Molenaar JJ. Cyclin-Dependent Kinase Inhibitor AT7519 as a Potential Drug for MYCN-Dependent Neuroblastoma. Clin Cancer Res. 2015 Nov 15;21(22):5100-9. doi: 10.1158/1078-0432.CCR-15-0313. Epub 2015 Jul 22. PMID: 26202950; PMCID: PMC4645454. 4. Alessandri AL, Duffin R, Leitch AE, Lucas CD, Sheldrake TA, Dorward DA, Hirani N, Pinho V, de Sousa LP, Teixeira MM, Lyons JF, Haslett C, Rossi AG. Induction of eosinophil apoptosis by the cyclin-dependent kinase inhibitor AT7519 promotes the resolution of eosinophil-dominant allergic inflammation. PLoS One. 2011;6(9):e25683. doi: 10.1371/journal.pone.0025683. Epub 2011 Sep 30. PMID: 21984938; PMCID: PMC3184151.

In vitro protocol:

In vivo protocol:

1. Dolman ME, Poon E, Ebus ME, den Hartog IJ, van Noesel CJ, Jamin Y, Hallsworth A, Robinson SP, Petrie K, Sparidans RW, Kok RJ, Versteeg R, Caron HN, Chesler L, Molenaar JJ. Cyclin-Dependent Kinase Inhibitor AT7519 as a Potential Drug for MYCN-Dependent Neuroblastoma. Clin Cancer Res. 2015 Nov 15;21(22):5100-9. doi: 10.1158/1078-0432.CCR-15-0313. Epub 2015 Jul 22. PMID: 26202950; PMCID: PMC4645454. 2. Alessandri AL, Duffin R, Leitch AE, Lucas CD, Sheldrake TA, Dorward DA, Hirani N, Pinho V, de Sousa LP, Teixeira MM, Lyons JF, Haslett C, Rossi AG. Induction of eosinophil apoptosis by the cyclin-dependent kinase inhibitor AT7519 promotes the resolution of eosinophil-dominant allergic inflammation. PLoS One. 2011;6(9):e25683. doi: 10.1371/journal.pone.0025683. Epub 2011 Sep 30. PMID: 21984938; PMCID: PMC3184151.

1: Santo L, Vallet S, Hideshima T, et al. AT7519, A novel small molecule multi-cyclin-dependent kinase inhibitor, induces apoptosis in multiple myeloma via GSK-3beta activation and RNA polymerase II inhibition. Oncogene. 2010;29(16):2325-2336. doi:10.1038/onc.2009.510 2: Squires MS, Feltell RE, Wallis NG, et al. Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines. Mol Cancer Ther. 2009;8(2):324-332. doi:10.1158/1535-7163.MCT-08-0890 3: Squires MS, Cooke L, Lock V, et al. AT7519, a cyclin-dependent kinase inhibitor, exerts its effects by transcriptional inhibition in leukemia cell lines and patient samples. Mol Cancer Ther. 2010;9(4):920-928. doi:10.1158/1535-7163.MCT-09-1071