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MedKoo Cat#: 406257 | Name: VE-821
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Description:

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

VE-821 is the first highly selective and potent ATR inhibitor. VE-821 inhibited radiation- and gemcitabine-induced phosphorylation of Chk1, confirming inhibition of ATR signaling. Consistently, VE-821 significantly enhanced the sensitivity of PSN-1, MiaPaCa-2 and primary PancM pancreatic cancer cells to radiation and gemcitabine under both normoxic and hypoxic conditions. ATR inhibition by VE-821 led to inhibition of radiation-induced G 2/M arrest in cancer cells.

Chemical Structure

VE-821
VE-821
CAS#1232410-49-9

Theoretical Analysis

MedKoo Cat#: 406257

Name: VE-821

CAS#: 1232410-49-9

Chemical Formula: C18H16N4O3S

Exact Mass: 368.0943

Molecular Weight: 368.41

Elemental Analysis: C, 58.68; H, 4.38; N, 15.21; O, 13.03; S, 8.70

Price and Availability

Size Price Availability Quantity
10mg USD 110.00 Ready to ship
25mg USD 200.00 Ready to ship
50mg USD 350.00 Ready to ship
100mg USD 600.00 Ready to ship
200mg USD 1,050.00 Ready to ship
500mg USD 1,850.00 Ready to ship
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Related CAS #
No Data
Synonym
VE821; VE-821; VE 821.
IUPAC/Chemical Name
3-amino-6-(4-(methylsulfonyl)phenyl)-N-phenylpyrazine-2-carboxamide
InChi Key
DUIHHZKTCSNTGM-UHFFFAOYSA-N
InChi Code
InChI=1S/C18H16N4O3S/c1-26(24,25)14-9-7-12(8-10-14)15-11-20-17(19)16(22-15)18(23)21-13-5-3-2-4-6-13/h2-11H,1H3,(H2,19,20)(H,21,23)
SMILES Code
O=C(C1=NC(C2=CC=C(S(=O)(C)=O)C=C2)=CN=C1N)NC3=CC=CC=C3
Appearance
White to beige 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, not in water
Shelf Life
>5 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
        
Biological target:
VE-821 is a potent ATP-competitive inhibitor of ATR with Ki/IC50 of 13 nM/26 nM.
In vitro activity:
HeLa, U2OS, and 1BR-hTERT (normal) cells were pre-treated with 1 μM VE-821 for 1 hour and irradiated with either high LET carbon ions or X-rays. Cell survival, cell cycle distribution, cell growth, and micronuclei formation were evaluated. VE-821 caused abrogation of G2/M checkpoint and forced irradiated cells to divide into daughter cells. It was also found that carbon ions caused a higher number of multiple micronuclei than X-rays, leading to decreased cell survival in tumor cells when treated with VE-821, while the survival of irradiated normal cells were not significantly affected by this inhibitor. Reference: Radiat Oncol. 2015 Aug 19;10:175. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/26286029/
In vivo activity:
Solvent mg/mL mM
Solubility
DMSO 50.0 135.72
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 368.41 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:
In vitro protocol:
1. Fujisawa H, Nakajima NI, Sunada S, Lee Y, Hirakawa H, Yajima H, Fujimori A, Uesaka M, Okayasu R. VE-821, an ATR inhibitor, causes radiosensitization in human tumor cells irradiated with high LET radiation. Radiat Oncol. 2015 Aug 19;10:175. doi: 10.1186/s13014-015-0464-y. PMID: 26286029; PMCID: PMC4554350. 2. Prevo R, Fokas E, Reaper PM, Charlton PA, Pollard JR, McKenna WG, Muschel RJ, Brunner TB. The novel ATR inhibitor VE-821 increases sensitivity of pancreatic cancer cells to radiation and chemotherapy. Cancer Biol Ther. 2012 Sep;13(11):1072-81. doi: 10.4161/cbt.21093. Epub 2012 Jul 24. PMID: 22825331; PMCID: PMC3461814.
In vivo protocol:
1: Smith HL, Willmore E, Prendergast L, Curtin NJ. ATR, CHK1 and WEE1 inhibitors cause homologous recombination repair deficiency to induce synthetic lethality with PARP inhibitors. Br J Cancer. 2024 Sep;131(5):905-917. doi: 10.1038/s41416-024-02745-0. Epub 2024 Jul 4. PMID: 38965423; PMCID: PMC11369084. 2: Jadav R, Weiland F, Noordermeer SM, Carroll T, Gao Y, Wang J, Zhou H, Lamoliatte F, Toth R, Macartney T, Brown F, Hastie CJ, Alabert C, van Attikum H, Zenke F, Masson JY, Rouse J. Chemo-Phosphoproteomic Profiling with ATR Inhibitors Berzosertib and Gartisertib Uncovers New Biomarkers and DNA Damage Response Regulators. Mol Cell Proteomics. 2024 Aug;23(8):100802. doi: 10.1016/j.mcpro.2024.100802. Epub 2024 Jun 15. PMID: 38880245; PMCID: PMC11338954. 3: Kansy AG, Ashry R, Mustafa AM, Alfayomy AM, Radsak MP, Zeyn Y, Bros M, Sippl W, Krämer OH. Pharmacological degradation of ATR induces antiproliferative DNA replication stress in leukemic cells. Mol Oncol. 2024 Aug;18(8):1958-1965. doi: 10.1002/1878-0261.13638. Epub 2024 Mar 22. PMID: 38520049; PMCID: PMC11306515. 4: Bayanbold K, Singhania M, Fath MA, Searby CC, Stolwijk JM, Henrich JB, Pulliam CF, Schoenfeld JD, Mapuskar KA, Sho S, Caster JM, Allen BG, Buettner GR, Spies M, Goswami PC, Petronek MS, Spitz DR. Depletion of Labile Iron Induces Replication Stress and Enhances Responses to Chemoradiation in Non-Small-Cell Lung Cancer. Antioxidants (Basel). 2023 Nov 15;12(11):2005. doi: 10.3390/antiox12112005. PMID: 38001858; PMCID: PMC10669787. 5: Zhao JL, Yang J, Li K, Chen Y, Tang M, Zhu HL, Nie CL, Yuan Z, Zhao XY. Abrogation of ATR function preferentially augments cisplatin-induced cytotoxicity in PTEN-deficient breast cancer cells. Chem Biol Interact. 2023 Nov 1;385:110740. doi: 10.1016/j.cbi.2023.110740. Epub 2023 Oct 5. PMID: 37802411. 6: Su H, Yuan Y, Tang J, Zhang Y, Wu H, Zhang Y, Liang J, Wang L, Zou X, Huang S, Zhang S, Lv Y. The ATR inhibitor VE-821 increases the sensitivity of gastric cancer cells to cisplatin. Transl Oncol. 2023 Oct;36:101743. doi: 10.1016/j.tranon.2023.101743. Epub 2023 Jul 28. PMID: 37517142; PMCID: PMC10400920. 7: Lohberger B, Glänzer D, Eck N, Stasny K, Falkner A, Leithner A, Georg D. The ATR Inhibitor VE-821 Enhances the Radiosensitivity and Suppresses DNA Repair Mechanisms of Human Chondrosarcoma Cells. Int J Mol Sci. 2023 Jan 24;24(3):2315. doi: 10.3390/ijms24032315. PMID: 36768638; PMCID: PMC9917087. 8: Huang Z, Yi L, Jin L, Chen J, Han Y, Zhang Y, Shi L. Systematic analysis of virus nucleic acid sensor DDX58 in malignant tumor. Front Microbiol. 2022 Dec 19;13:1085086. doi: 10.3389/fmicb.2022.1085086. PMID: 36601407; PMCID: PMC9807228. 9: Smith HL, Willmore E, Mukhopadhyay A, Drew Y, Curtin NJ. Differences in Durability of PARP Inhibition by Clinically Approved PARP Inhibitors: Implications for Combinations and Scheduling. Cancers (Basel). 2022 Nov 12;14(22):5559. doi: 10.3390/cancers14225559. PMID: 36428653; PMCID: PMC9688250. 10: Saha S, Rundle S, Kotsopoulos IC, Begbie J, Howarth R, Pappworth IY, Mukhopadhyay A, Kucukmetin A, Marchbank KJ, Curtin N. Determining the Potential of DNA Damage Response (DDR) Inhibitors in Cervical Cancer Therapy. Cancers (Basel). 2022 Sep 1;14(17):4288. doi: 10.3390/cancers14174288. PMID: 36077823; PMCID: PMC9454916. 11: Bradbury A, Zenke FT, Curtin NJ, Drew Y. The Role of ATR Inhibitors in Ovarian Cancer: Investigating Predictive Biomarkers of Response. Cells. 2022 Aug 1;11(15):2361. doi: 10.3390/cells11152361. PMID: 35954206; PMCID: PMC9367423. 12: Hirt CK, Booij TH, Grob L, Simmler P, Toussaint NC, Keller D, Taube D, Ludwig V, Goryachkin A, Pauli C, Lenggenhager D, Stekhoven DJ, Stirnimann CU, Endhardt K, Ringnalda F, Villiger L, Siebenhüner A, Karkampouna S, De Menna M, Beshay J, Klett H, Kruithof-de Julio M, Schüler J, Schwank G. Drug screening and genome editing in human pancreatic cancer organoids identifies drug-gene interactions and candidates for off-label treatment. Cell Genom. 2022 Feb;2(2):100095. doi: 10.1016/j.xgen.2022.100095. PMID: 35187519; PMCID: PMC7612395. 13: Han L, Huang C, Wang X, Tong D. The RNA-binding protein GRSF1 promotes hepatocarcinogenesis via competitively binding to YY1 mRNA with miR-30e-5p. J Exp Clin Cancer Res. 2022 Jan 8;41(1):17. doi: 10.1186/s13046-021-02217-w. Erratum in: J Exp Clin Cancer Res. 2022 May 25;41(1):181. doi: 10.1186/s13046-022-02392-4. PMID: 34998399; PMCID: PMC8742353. 14: Moon SH, Park NS, Noh MH, Kim YS, Cheong SH, Hur DY. Olaparib-induced Apoptosis Through EBNA1-ATR-p38 MAPK Signaling Pathway in Epstein-Barr Virus- positive Gastric Cancer Cells. Anticancer Res. 2022 Jan;42(1):555-563. doi: 10.21873/anticanres.15513. PMID: 34969765. 15: King D, Southgate HED, Roetschke S, Gravells P, Fields L, Watson JB, Chen L, Chapman D, Harrison D, Yeomanson D, Curtin NJ, Tweddle DA, Bryant HE. Increased Replication Stress Determines ATR Inhibitor Sensitivity in Neuroblastoma Cells. Cancers (Basel). 2021 Dec 10;13(24):6215. doi: 10.3390/cancers13246215. PMID: 34944835; PMCID: PMC8699051. 16: Ghelli Luserna Di Rorà A, Ghetti M, Ledda L, Ferrari A, Bocconcelli M, Padella A, Napolitano R, Fontana MC, Liverani C, Imbrogno E, Bochicchio MT, Paganelli M, Robustelli V, Sanogo S, Cerchione C, Fumagalli M, Rondoni M, Imovilli A, Musuraca G, Martinelli G, Simonetti G. Exploring the ATR-CHK1 pathway in the response of doxorubicin-induced DNA damages in acute lymphoblastic leukemia cells. Cell Biol Toxicol. 2023 Jun;39(3):795-811. doi: 10.1007/s10565-021-09640-x. Epub 2021 Sep 14. Erratum in: Cell Biol Toxicol. 2024 Aug 31;40(1):73. doi: 10.1007/s10565-024-09913-1. PMID: 34519926; PMCID: PMC10406704. 17: Permata TBM, Sato H, Gu W, Kakoti S, Uchihara Y, Yoshimatsu Y, Sato I, Kato R, Yamauchi M, Suzuki K, Oike T, Tsushima Y, Gondhowiardjo S, Ohno T, Yasuhara T, Shibata A. High linear energy transfer carbon-ion irradiation upregulates PD-L1 expression more significantly than X-rays in human osteosarcoma U2OS cells. J Radiat Res. 2021 Sep 13;62(5):773-781. doi: 10.1093/jrr/rrab050. PMID: 34196706; PMCID: PMC8438258. 18: Nikolakopoulou A, Soni A, Habibi M, Karaiskos P, Pantelias G, Terzoudi GI, Iliakis G. G2/M Checkpoint Abrogation With Selective Inhibitors Results in Increased Chromatid Breaks and Radiosensitization of 82-6 hTERT and RPE Human Cells. Front Public Health. 2021 May 28;9:675095. doi: 10.3389/fpubh.2021.675095. PMID: 34123995; PMCID: PMC8193504. 19: Zhang JQJ, Saravanabavan S, Rangan GK. Effect of Reducing Ataxia- Telangiectasia Mutated (ATM) in Experimental Autosomal Dominant Polycystic Kidney Disease. Cells. 2021 Mar 3;10(3):532. doi: 10.3390/cells10030532. PMID: 33802342; PMCID: PMC8000896. 20: Moolmuang B, Ruchirawat M. The antiproliferative effects of ataxia- telangiectasia mutated and ATM- and Rad3-related inhibitions and their enhancements with the cytotoxicity of DNA damaging agents in cholangiocarcinoma cells. J Pharm Pharmacol. 2021 Mar 1;73(1):40-51. doi: 10.1093/jpp/rgaa050. PMID: 33791808.