MK-1775
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MedKoo CAT#: 201912

CAS#: 955365-80-7

Description: MK-1775, also known as adavosertib, AZD-1775, is a WEE1 inhibitor, is also a small molecule inhibitor of the tyrosine kinase WEE1 with potential antineoplastic sensitizing activity. MK-1775 selectively targets and inhibits WEE1, a tyrosine kinase that phosphorylates cyclin-dependent kinase 1 (CDC2) to inactivate the CDC2/cyclin B complex. Inhibition of WEE1 activity prevents the phosphorylation of CDC2 and impairs the G2 DNA damage checkpoint. This may lead to apoptosis upon treatment with DNA damaging chemotherapeutic agents.


Chemical Structure

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MK-1775
CAS# 955365-80-7

Theoretical Analysis

MedKoo Cat#: 201912
Name: MK-1775
CAS#: 955365-80-7
Chemical Formula: C27H32N8O2
Exact Mass: 500.26482
Molecular Weight: 500.6
Elemental Analysis: C, 64.78; H, 6.44; N, 22.38; O, 6.39

Price and Availability

Size Price Availability Quantity
10.0mg USD 90.0 Ready to ship
100.0mg USD 150.0 Ready to ship
200.0mg USD 250.0 Ready to ship
500.0mg USD 550.0 Ready to ship
1.0g USD 950.0 Ready to ship
2.0g USD 1650.0 Ready to ship
5.0g USD 3650.0 Ready to ship
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Synonym: MK-1775; MK1775; MK 1775; AZD1775; AZD-1775; AZD 1775; adavosertib.

IUPAC/Chemical Name: 2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[3,4-d]pyrimidin-3(2H)-one

InChi Key: BKWJAKQVGHWELA-UHFFFAOYSA-N

InChi Code: InChI=1S/C27H32N8O2/c1-5-13-34-25(36)21-18-28-26(29-19-9-11-20(12-10-19)33-16-14-32(4)15-17-33)31-24(21)35(34)23-8-6-7-22(30-23)27(2,3)37/h5-12,18,37H,1,13-17H2,2-4H3,(H,28,29,31)

SMILES Code: O=C1N(CC=C)N(C2=NC(C(C)(O)C)=CC=C2)C3=NC(NC4=CC=C(N5CCN(C)CC5)C=C4)=NC=C31

Appearance: Yellow 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: >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

Biological target: Wee1 inhibitor with an IC50 of 5.2 nM.
In vitro activity: MK-1775 induced apoptosis in both AML cell lines and diagnostic blast samples, accompanied by decreased phosphorylation of CDK1 and CDK2 on Tyr-15 and increased DNA double-strand breaks (DSBs). Time-course experiments, using AML cell lines, revealed a time-dependent increase in DNA DSBs, activation of CHK1 and subsequent apoptosis following MK-1775 treatment, which could be attenuated by a CDK1/2 inhibitor, Roscovitine. Simultaneous inhibition of CHK1 and Wee1 resulted in synergistic anti-leukemic activity in both AML cell lines and primary patient samples ex vivo. Reference: J Hematol Oncol. 2014; 7: 53. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4237862/
In vivo activity: GBM22 (IC50 = 68 nM) was significantly more sensitive to MK-1775 compared to 5 other GBM xenograft lines including GBM6 (IC50 >300 nM), and this was associated with a significant difference in pan-nuclear γH2AX staining between treated GBM22 (81% cells positive) and GBM6 (20% cells positive) cells. However, there was no sensitizing effect of MK-1775 when combined with TMZ in vitro. In an orthotopic GBM22 model, MK-1775 was ineffective when combined with TMZ, while in a flank model of GBM22, MK-1775 exhibited both single agent and combinatorial activity with TMZ. Consistent with limited drug delivery into orthotopic tumors, the normal brain to whole blood ratio following a single MK-1775 dose was 5%, and MALDI-MS imaging demonstrated heterogeneous and markedly lower MK-1775 distribution in orthotopic as compared to heterotopic GBM22 tumors. Reference: data is copied from Clin Cancer Res. 2015 Apr 15; 21(8): 1916–1924. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401631/ Note: The information listed here was extracted from literature. MedKoo has not independently retested and confirmed the accuracy of these methods. Customer should use it just for a reference only.

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 100.0 199.76

Preparing Stock Solutions

The following data is based on the product molecular weight 500.6 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: Pokorny JL, Calligaris D, Gupta SK, Iyekegbe DO Jr, Mueller D, Bakken KK, Carlson BL, Schroeder MA, Evans DL, Lou Z, Decker PA, Eckel-Passow JE, Pucci V, Ma B, Shumway SD, Elmquist WF, Agar NY, Sarkaria JN. The Efficacy of the Wee1 Inhibitor MK-1775 Combined with Temozolomide Is Limited by Heterogeneous Distribution across the Blood-Brain Barrier in Glioblastoma. Clin Cancer Res. 2015 Apr 15;21(8):1916-24. doi: 10.1158/1078-0432.CCR-14-2588. Epub 2015 Jan 21. PMID: 25609063; PMCID: PMC4401631.
In vitro protocol: 1. Pokorny JL, Calligaris D, Gupta SK, Iyekegbe DO Jr, Mueller D, Bakken KK, Carlson BL, Schroeder MA, Evans DL, Lou Z, Decker PA, Eckel-Passow JE, Pucci V, Ma B, Shumway SD, Elmquist WF, Agar NY, Sarkaria JN. The Efficacy of the Wee1 Inhibitor MK-1775 Combined with Temozolomide Is Limited by Heterogeneous Distribution across the Blood-Brain Barrier in Glioblastoma. Clin Cancer Res. 2015 Apr 15;21(8):1916-24. doi: 10.1158/1078-0432.CCR-14-2588. Epub 2015 Jan 21. PMID: 25609063; PMCID: PMC4401631. 2. Qi W, Xie C, Li C, Caldwell JT, Edwards H, Taub JW, Wang Y, Lin H, Ge Y. CHK1 plays a critical role in the anti-leukemic activity of the wee1 inhibitor MK-1775 in acute myeloid leukemia cells. J Hematol Oncol. 2014 Aug 1;7:53. doi: 10.1186/s13045-014-0053-9. PMID: 25084614; PMCID: PMC4237862.
In vivo protocol: 1. Pokorny JL, Calligaris D, Gupta SK, Iyekegbe DO Jr, Mueller D, Bakken KK, Carlson BL, Schroeder MA, Evans DL, Lou Z, Decker PA, Eckel-Passow JE, Pucci V, Ma B, Shumway SD, Elmquist WF, Agar NY, Sarkaria JN. The Efficacy of the Wee1 Inhibitor MK-1775 Combined with Temozolomide Is Limited by Heterogeneous Distribution across the Blood-Brain Barrier in Glioblastoma. Clin Cancer Res. 2015 Apr 15;21(8):1916-24. doi: 10.1158/1078-0432.CCR-14-2588. Epub 2015 Jan 21. PMID: 25609063; PMCID: PMC4401631. 2. Wang G, Niu X, Zhang W, Caldwell JT, Edwards H, Chen W, Taub JW, Zhao L, Ge Y. Synergistic antitumor interactions between MK-1775 and panobinostat in preclinical models of pancreatic cancer. Cancer Lett. 2015 Jan 28;356(2 Pt B):656-68. doi: 10.1016/j.canlet.2014.10.015. Epub 2014 Oct 18. PMID: 25458954; PMCID: PMC4282784.

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1: Hoffmann MJ, Meneceur S, Hommel K, Schulz WA, Niegisch G. Downregulation of Cell Cycle and Checkpoint Genes by Class I HDAC Inhibitors Limits Synergism with G2/M Checkpoint Inhibitor MK-1775 in Bladder Cancer Cells. Genes (Basel). 2021 Feb 11;12(2):260. doi: 10.3390/genes12020260. PMID: 33670166; PMCID: PMC7916885.

2: Barbosa RSS, Dantonio PM, Guimarães T, de Oliveira MB, Fook Alves VL, Sandes AF, Fernando RC, Colleoni GWB. Sequential combination of bortezomib and WEE1 inhibitor, MK-1775, induced apoptosis in multiple myeloma cell lines. Biochem Biophys Res Commun. 2019 Nov 12;519(3):597-604. doi: 10.1016/j.bbrc.2019.08.163. Epub 2019 Sep 17. PMID: 31540690.

3: Duan Y, Dong X, Nie J, Li P, Lu F, Ma D, Ji C. Wee1 kinase inhibitor MK-1775 induces apoptosis of acute lymphoblastic leukemia cells and enhances the efficacy of doxorubicin involving downregulation of Notch pathway. Oncol Lett. 2018 Oct;16(4):5473-5481. doi: 10.3892/ol.2018.9291. Epub 2018 Aug 10. PMID: 30250620; PMCID: PMC6144465.

4: Chen G, Zhang B, Xu H, Sun Y, Shi Y, Luo Y, Jia H, Wang F. Suppression of Sirt1 sensitizes lung cancer cells to WEE1 inhibitor MK-1775-induced DNA damage and apoptosis. Oncogene. 2017 Dec 14;36(50):6863-6872. doi: 10.1038/onc.2017.297. Epub 2017 Sep 4. PMID: 28869605.

5: Ebeid K, Ho GN, Salem AK. HPLC-UV method for simultaneous determination of MK-1775 and AZD-7762 in both acetonitrile-aqueous solution and mouse plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Feb 15;1044-1045:70-76. doi: 10.1016/j.jchromb.2016.12.031. Epub 2016 Dec 30. PMID: 28088043; PMCID: PMC5296315.

6: Ma H, Takahashi A, Sejimo Y, Adachi A, Kubo N, Isono M, Yoshida Y, Kanai T, Ohno T, Nakano T. Targeting of Carbon Ion-Induced G2 Checkpoint Activation in Lung Cancer Cells Using Wee-1 Inhibitor MK-1775. Radiat Res. 2015 Dec;184(6):660-9. doi: 10.1667/RR14171.1. Epub 2015 Dec 8. Erratum in: Radiat Res. 2016 Feb;185(2):e52. PMID: 26645158.

7: Qi W, Zhang W, Edwards H, Chu R, Madlambayan GJ, Taub JW, Wang Z, Wang Y, Li C, Lin H, Ge Y. Synergistic anti-leukemic interactions between panobinostat and MK-1775 in acute myeloid leukemia ex vivo. Cancer Biol Ther. 2015;16(12):1784-93. doi: 10.1080/15384047.2015.1095406. PMID: 26529495; PMCID: PMC4847803.

8: Do K, Wilsker D, Ji J, Zlott J, Freshwater T, Kinders RJ, Collins J, Chen AP, Doroshow JH, Kummar S. Phase I Study of Single-Agent AZD1775 (MK-1775), a Wee1 Kinase Inhibitor, in Patients With Refractory Solid Tumors. J Clin Oncol. 2015 Oct 20;33(30):3409-15. doi: 10.1200/JCO.2014.60.4009. Epub 2015 May 11. PMID: 25964244; PMCID: PMC4606059.

9: Pokorny JL, Calligaris D, Gupta SK, Iyekegbe DO Jr, Mueller D, Bakken KK, Carlson BL, Schroeder MA, Evans DL, Lou Z, Decker PA, Eckel-Passow JE, Pucci V, Ma B, Shumway SD, Elmquist WF, Agar NY, Sarkaria JN. The Efficacy of the Wee1 Inhibitor MK-1775 Combined with Temozolomide Is Limited by Heterogeneous Distribution across the Blood-Brain Barrier in Glioblastoma. Clin Cancer Res. 2015 Apr 15;21(8):1916-24. doi: 10.1158/1078-0432.CCR-14-2588. Epub 2015 Jan 21. PMID: 25609063; PMCID: PMC4401631.

10: Wang G, Niu X, Zhang W, Caldwell JT, Edwards H, Chen W, Taub JW, Zhao L, Ge Y. Synergistic antitumor interactions between MK-1775 and panobinostat in preclinical models of pancreatic cancer. Cancer Lett. 2015 Jan 28;356(2 Pt B):656-68. doi: 10.1016/j.canlet.2014.10.015. Epub 2014 Oct 18. PMID: 25458954; PMCID: PMC4282784.

11: Qi W, Xie C, Li C, Caldwell JT, Edwards H, Taub JW, Wang Y, Lin H, Ge Y. CHK1 plays a critical role in the anti-leukemic activity of the wee1 inhibitor MK-1775 in acute myeloid leukemia cells. J Hematol Oncol. 2014 Aug 1;7:53. doi: 10.1186/s13045-014-0053-9. PMID: 25084614; PMCID: PMC4237862.

12: Guertin AD, Li J, Liu Y, Hurd MS, Schuller AG, Long B, Hirsch HA, Feldman I, Benita Y, Toniatti C, Zawel L, Fawell SE, Gilliland DG, Shumway SD. Preclinical evaluation of the WEE1 inhibitor MK-1775 as single-agent anticancer therapy. Mol Cancer Ther. 2013 Aug;12(8):1442-52. doi: 10.1158/1535-7163.MCT-13-0025. Epub 2013 May 22. PMID: 23699655.

13: Kreahling JM, Foroutan P, Reed D, Martinez G, Razabdouski T, Bui MM, Raghavan M, Letson D, Gillies RJ, Altiok S. Wee1 inhibition by MK-1775 leads to tumor inhibition and enhances efficacy of gemcitabine in human sarcomas. PLoS One. 2013;8(3):e57523. doi: 10.1371/journal.pone.0057523. Epub 2013 Mar 8. PMID: 23520471; PMCID: PMC3592874.

14: Xu Y, Fang W, Zeng W, Leijen S, Woolf EJ. Evaluation of dried blood spot (DBS) technology versus plasma analysis for the determination of MK-1775 by HILIC-MS/MS in support of clinical studies. Anal Bioanal Chem. 2012 Dec;404(10):3037-48. doi: 10.1007/s00216-012-6440-6. Epub 2012 Oct 26. PMID: 23099526.

15: Sarcar B, Kahali S, Prabhu AH, Shumway SD, Xu Y, Demuth T, Chinnaiyan P. Targeting radiation-induced G(2) checkpoint activation with the Wee-1 inhibitor MK-1775 in glioblastoma cell lines. Mol Cancer Ther. 2011 Dec;10(12):2405-14. doi: 10.1158/1535-7163.MCT-11-0469. Epub 2011 Oct 12. PMID: 21992793; PMCID: PMC5753756.

16: Bridges KA, Hirai H, Buser CA, Brooks C, Liu H, Buchholz TA, Molkentine JM, Mason KA, Meyn RE. MK-1775, a novel Wee1 kinase inhibitor, radiosensitizes p53-defective human tumor cells. Clin Cancer Res. 2011 Sep 1;17(17):5638-48. doi: 10.1158/1078-0432.CCR-11-0650. Epub 2011 Jul 28. PMID: 21799033; PMCID: PMC3167033.

17: Rajeshkumar NV, De Oliveira E, Ottenhof N, Watters J, Brooks D, Demuth T, Shumway SD, Mizuarai S, Hirai H, Maitra A, Hidalgo M. MK-1775, a potent Wee1 inhibitor, synergizes with gemcitabine to achieve tumor regressions, selectively in p53-deficient pancreatic cancer xenografts. Clin Cancer Res. 2011 May 1;17(9):2799-806. doi: 10.1158/1078-0432.CCR-10-2580. Epub 2011 Mar 9. PMID: 21389100; PMCID: PMC3307341.

18: Hirai H, Arai T, Okada M, Nishibata T, Kobayashi M, Sakai N, Imagaki K, Ohtani J, Sakai T, Yoshizumi T, Mizuarai S, Iwasawa Y, Kotani H. MK-1775, a small molecule Wee1 inhibitor, enhances anti-tumor efficacy of various DNA- damaging agents, including 5-fluorouracil. Cancer Biol Ther. 2010 Apr 1;9(7):514-22. doi: 10.4161/cbt.9.7.11115. Epub 2010 Apr 1. PMID: 20107315.

19: Hirai H, Iwasawa Y, Okada M, Arai T, Nishibata T, Kobayashi M, Kimura T, Kaneko N, Ohtani J, Yamanaka K, Itadani H, Takahashi-Suzuki I, Fukasawa K, Oki H, Nambu T, Jiang J, Sakai T, Arakawa H, Sakamoto T, Sagara T, Yoshizumi T, Mizuarai S, Kotani H. Small-molecule inhibition of Wee1 kinase by MK-1775 selectively sensitizes p53-deficient tumor cells to DNA-damaging agents. Mol Cancer Ther. 2009 Nov;8(11):2992-3000. doi: 10.1158/1535-7163.MCT-09-0463. Epub 2009 Nov 3. PMID: 19887545.

MK-1775

10.0mg / USD 90.0


Additional Information