Sotrastaurin
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MedKoo CAT#: 205809

CAS#: 425637-18-9

Description: Sotrastaurin, also known as AEB-071, is an orally available pan-protein kinase C (PKC) inhibitor with potential immunosuppressive and antineoplastic activities. Sotrastaurin inhibits both T- and B-cell activations via PKC theta and beta isozymes, respectively. Both PKCs are important in the activation of nuclear factor-kappaB (NF-kB). Inhibition of PKC beta in B-cells results in prevention of NF-kB-mediated signaling and down regulation of NF-kB target genes. This may eventually lead to an induction of G1 cell cycle arrest and tumor cell apoptosis in susceptible tumor cells. This agent may act synergistically with other chemotherapeutic agents.


Price and Availability

Size
Price

5mg
USD 250
Size
Price

10mg
USD 450
Size
Price

Sotrastaurin, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 205809
Name: Sotrastaurin
CAS#: 425637-18-9
Chemical Formula: C25H22N6O2
Exact Mass: 438.18042
Molecular Weight: 438.48118
Elemental Analysis: C, 68.48; H, 5.06; N, 19.17; O, 7.30


Synonym: AEB071; AEB071; AEB 071. Sotrastaurin.

IUPAC/Chemical Name: 3-(1H-indol-3-yl)-4-(2-(4-methylpiperazin-1-yl)quinazolin-4-yl)-1H-pyrrole-2,5-dione

InChi Key: OAVGBZOFDPFGPJ-UHFFFAOYSA-N

InChi Code: InChI=1S/C25H22N6O2/c1-30-10-12-31(13-11-30)25-27-19-9-5-3-7-16(19)22(28-25)21-20(23(32)29-24(21)33)17-14-26-18-8-4-2-6-15(17)18/h2-9,14,26H,10-13H2,1H3,(H,29,32,33)

SMILES Code: O=C(C(C1=CNC2=C1C=CC=C2)=C3C4=C5C=CC=CC5=NC(N6CCN(C)CC6)=N4)NC3=O


Technical Data

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, 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).

Harmonized System Code:
293490


Additional Information

  
 
 
 


References

1: Bigaud M, Wieczorek G, Beerli C, Audet M, Blancher A, Heusser C, Morris RE, Wagner J. Sotrastaurin (AEB071) alone and in combination with cyclosporine A prolongs survival times of non-human primate recipients of life-supporting kidney allografts. Transplantation. 2012 Jan 27;93(2):156-64. PubMed PMID: 22179400.

2: Yamashita K, Todo S. Sotrastaurin, a new selective protein kinase C inhibitor, on the way. Transplantation. 2012 Jan 27;93(2):146-7. PubMed PMID: 22129763.

3: Merani S, McCall M, Pawlick RL, Edgar RL, Davis J, Toso C, Emamaullee JA, Kin T, Shapiro AM. AEB071 (sotrastaurin) does not exhibit toxic effects on human islets in vitro, nor after transplantation into immunodeficient mice. Islets. 2011 Nov-Dec;3(6):338-43. Epub 2011 Nov 1. PubMed PMID: 21934354.

4: von Hahn T, Schulze A, Chicano Wust I, Heidrich B, Becker T, Steinmann E, Helfritz FA, Rohrmann K, Urban S, Manns MP, Pietschmann T, Ciesek S. The novel immunosuppressive protein kinase C inhibitor sotrastaurin has no pro-viral effects on the replication cycle of hepatitis B or C virus. PLoS One. 2011;6(9):e24142. Epub 2011 Sep 1. PubMed PMID: 21909416; PubMed Central PMCID: PMC3164709.

5: Kamo N, Shen XD, Ke B, Busuttil RW, Kupiec-Weglinski JW. Sotrastaurin, a protein kinase C inhibitor, ameliorates ischemia and reperfusion injury in rat orthotopic liver transplantation. Am J Transplant. 2011 Nov;11(11):2499-507. doi: 10.1111/j.1600-6143.2011.03700.x. Epub 2011 Aug 30. PubMed PMID: 21883905.

6: Fang YH, Joo DJ, Lim BJ, Huh KH, Kim MS, Suh H, Kim YS. The effects of AEB071 (sotrastaurin) with tacrolimus on rat heterotopic cardiac allograft rejection and survival. J Surg Res. 2011 Nov;171(1):e133-7. Epub 2011 Jul 21. PubMed PMID: 21816421.

7: Wagner J, von Matt P, Faller B, Cooke NG, Albert R, Sedrani R, Wiegand H, Jean C, Beerli C, Weckbecker G, Evenou JP, Zenke G, Cottens S. Structure-activity relationship and pharmacokinetic studies of sotrastaurin (AEB071), a promising novel medicine for prevention of graft rejection and treatment of psoriasis. J Med Chem. 2011 Sep 8;54(17):6028-39. Epub 2011 Aug 8. PubMed PMID: 21797275.

8: Getts DR, Shankar S, Chastain EM, Martin A, Getts MT, Wood K, Miller SD. Current landscape for T-cell targeting in autoimmunity and transplantation. Immunotherapy. 2011 Jul;3(7):853-70. Review. PubMed PMID: 21751954.

9: Hoogduijn MJ, Roemeling-van Rhijn M, Korevaar SS, Engela AU, Weimar W, Baan CC. Immunological aspects of allogeneic and autologous mesenchymal stem cell therapies. Hum Gene Ther. 2011 Dec;22(12):1587-91. Epub 2011 Aug 10. PubMed PMID: 21732766.

10: Silva HT Jr, Felipe CR, Abbud-Filho M, Garcia V, Medina-Pestana JO. The emerging role of Brazil in clinical trial conduct for transplantation. Am J Transplant. 2011 Jul;11(7):1368-75. doi: 10.1111/j.1600-6143.2011.03564.x. Epub 2011 Jun 10. Review. PubMed PMID: 21668630.

11: Meier-Kriesche HU, Kaplan B. The search for CNI-free immunosuppression: no free lunch. Am J Transplant. 2011 Jul;11(7):1355-6. doi: 10.1111/j.1600-6143.2011.03541.x. Epub 2011 May 12. PubMed PMID: 21564526.

12: Friman S, Arns W, Nashan B, Vincenti F, Banas B, Budde K, Cibrik D, Chan L, Klempnauer J, Mulgaonkar S, Nicholson M, Wahlberg J, Wissing KM, Abrams K, Witte S, Woodle ES. Sotrastaurin, a novel small molecule inhibiting protein-kinase C: randomized phase II study in renal transplant recipients. Am J Transplant. 2011 Jul;11(7):1444-55. doi: 10.1111/j.1600-6143.2011.03538.x. Epub 2011 May 12. PubMed PMID: 21564523.

13: Kahan BD. Frontiers in immunosuppression. Transplant Proc. 2011 Apr;43(3):822-5. PubMed PMID: 21486607.

14: Naylor TL, Tang H, Ratsch BA, Enns A, Loo A, Chen L, Lenz P, Waters NJ, Schuler W, Dörken B, Yao YM, Warmuth M, Lenz G, Stegmeier F. Protein kinase C inhibitor sotrastaurin selectively inhibits the growth of CD79 mutant diffuse large B-cell lymphomas. Cancer Res. 2011 Apr 1;71(7):2643-53. Epub 2011 Feb 15. PubMed PMID: 21324920.

15: Kovarik JM, Steiger JU, Grinyo JM, Rostaing L, Arns W, Dantal J, Proot P, Budde K; Sotrastaurin Renal Transplant Study Group. Pharmacokinetics of sotrastaurin combined with tacrolimus or mycophenolic acid in de novo kidney transplant recipients. Transplantation. 2011 Feb 15;91(3):317-22. PubMed PMID: 21157403.

16: Matz M, Naik M, Mashreghi MF, Glander P, Neumayer HH, Budde K. Evaluation of the novel protein kinase C inhibitor sotrastaurin as immunosuppressive therapy after renal transplantation. Expert Opin Drug Metab Toxicol. 2011 Jan;7(1):103-13. Epub 2010 Dec 8. Review. PubMed PMID: 21142580.

17: Kovarik JM, Neuhaus P, Cillo U, Weber M, Stitah S, Gatlik E, Meiser K, Slade A. Sotrastaurin single-dose pharmacokinetics in de novo liver transplant recipients. Transpl Int. 2011 Mar;24(3):276-83. doi: 10.1111/j.1432-2277.2010.01196.x. Epub 2010 Dec 7. PubMed PMID: 21134243.

18: Kovarik JM, Slade A. Overview of sotrastaurin clinical pharmacokinetics. Ther Drug Monit. 2010 Oct;32(5):540-3. Review. PubMed PMID: 20683390.

19: Kovarik JM, Stitah S, Slade A, Vitaliti A, Straube F, Grenet O, Winter S, Sfikas N, Seiberling M. Sotrastaurin and cyclosporine drug interaction study in healthy subjects. Biopharm Drug Dispos. 2010 Jul;31(5-6):331-9. PubMed PMID: 20578209.

20: Fang YH, Joo DJ, Lim BJ, Kim JY, Kim MS, Jeong HJ, Kim YS. AEB-071 versus tacrolimus monotherapy to prevent acute cardiac allograft rejection in the rat: a preliminary report. Transplant Proc. 2010 Apr;42(3):976-9. PubMed PMID: 20430219.

21: Cooper JE, Wiseman AC. Novel immunosuppressive agents in kidney transplantation. Clin Nephrol. 2010 May;73(5):333-43. Review. PubMed PMID: 20420793.

22: Kovarik JM, Stitah S, Slade A, Vitaliti A, Straube F, Grenet O, Winter S, Sfikas N, Seiberling M. Sotrastaurin and tacrolimus coadministration: effects on pharmacokinetics and biomarker responses. J Clin Pharmacol. 2010 Nov;50(11):1260-6. Epub 2010 Apr 12. PubMed PMID: 20386017.

23: Kovarik JM, Bartlett M, Rordorf C, Antunes MC, Winter S, Marbach P, van Marle S. Sotrastaurin and everolimus pharmacokinetics after single-dose coadministration. Int J Clin Pharmacol Ther. 2010 Feb;48(2):103-8. PubMed PMID: 20137762.

24: Mariat C. [The new drugs in development for kidney transplantation]. Nephrol Ther. 2009 Dec;5 Suppl 6:S400-4. French. PubMed PMID: 20129453.

25: Budde K, Sommerer C, Becker T, Asderakis A, Pietruck F, Grinyo JM, Rigotti P, Dantal J, Ng J, Barten MJ, Weber M. Sotrastaurin, a novel small molecule inhibiting protein kinase C: first clinical results in renal-transplant recipients. Am J Transplant. 2010 Mar;10(3):571-81. Epub 2010 Jan 29. PubMed PMID: 20121745.

26: Matz M, Weber U, Mashreghi MF, Lorkowski C, Ladhoff J, Kramer S, Neumayer HH, Budde K. Effects of the new immunosuppressive agent AEB071 on human immune cells. Nephrol Dial Transplant. 2010 Jul;25(7):2159-67. Epub 2010 Jan 25. PubMed PMID: 20100729.

27: Weckbecker G, Pally C, Beerli C, Burkhart C, Wieczorek G, Metzler B, Morris RE, Wagner J, Bruns C. Effects of the novel protein kinase C inhibitor AEB071 (Sotrastaurin) on rat cardiac allograft survival using single agent treatment or combination therapy with cyclosporine, everolimus or FTY720. Transpl Int. 2010 May 1;23(5):543-52. Epub 2009 Dec 9. PubMed PMID: 20003043.

28: Sommerer C, Zeier M. AEB071--a promising immunosuppressive agent. Clin Transplant. 2009 Dec;23 Suppl 21:15-8. Review. PubMed PMID: 19930311.

29: Verkaar F, Blankesteijn WM, Smits JF, Zaman GJ. beta-Galactosidase enzyme fragment complementation for the measurement of Wnt/beta-catenin signaling. FASEB J. 2010 Apr;24(4):1205-17. Epub 2009 Nov 25. PubMed PMID: 19940259.

30: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2009 Sep;31(7):463-93. PubMed PMID: 19907722.

31: Manicassamy S. Sotrastaurin, a protein kinase C inhibitor for the prevention of transplant rejection and treatment of psoriasis. Curr Opin Investig Drugs. 2009 Nov;10(11):1225-35. Review. PubMed PMID: 19876790.

32: Wagner J, von Matt P, Sedrani R, Albert R, Cooke N, Ehrhardt C, Geiser M, Rummel G, Stark W, Strauss A, Cowan-Jacob SW, Beerli C, Weckbecker G, Evenou JP, Zenke G, Cottens S. Discovery of 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione (AEB071), a potent and selective inhibitor of protein kinase C isotypes. J Med Chem. 2009 Oct 22;52(20):6193-6. PubMed PMID: 19827831.

33: Kovarik JM, Huang HL, Slade A, Sfikas N, Chandler PA. The effect on sotrastaurin pharmacokinetics of strong CYP3A inhibition by ketoconazole. Br J Clin Pharmacol. 2009 Sep;68(3):381-5. PubMed PMID: 19740395; PubMed Central PMCID: PMC2766477.

34: Evenou JP, Wagner J, Zenke G, Brinkmann V, Wagner K, Kovarik J, Welzenbach KA, Weitz-Schmidt G, Guntermann C, Towbin H, Cottens S, Kaminski S, Letschka T, Lutz-Nicoladoni C, Gruber T, Hermann-Kleiter N, Thuille N, Baier G. The potent protein kinase C-selective inhibitor AEB071 (sotrastaurin) represents a new class of immunosuppressive agents affecting early T-cell activation. J Pharmacol Exp Ther. 2009 Sep;330(3):792-801. Epub 2009 Jun 2. PubMed PMID: 19491325.

35: Vincenti F, Kirk AD. What's next in the pipeline. Am J Transplant. 2008 Oct;8(10):1972-81. Review. PubMed PMID: 18828764.

36: Skvara H, Dawid M, Kleyn E, Wolff B, Meingassner JG, Knight H, Dumortier T, Kopp T, Fallahi N, Stary G, Burkhart C, Grenet O, Wagner J, Hijazi Y, Morris RE, McGeown C, Rordorf C, Griffiths CE, Stingl G, Jung T. The PKC inhibitor AEB071 may be a therapeutic option for psoriasis. J Clin Invest. 2008 Sep;118(9):3151-9. PubMed PMID: 18688284; PubMed Central PMCID: PMC2496962.

37: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 Apr;30(3):231-51. PubMed PMID: 18597009.