WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H407161
CAS#: 612847-09-3
Description: AKT inhibitor VIII, also known as AKTi-1/2, is a potent, selective and ell permeable, allosteric inhibitor of Akt 1 and 2, which efficiently inhibits CaMKIα activity and aryl hydrocarbon receptor pathway. AKT inhibitor VIII suppresses hyperthermia-induced Ndrg2 phosphorylation in gastric cancer cells. AKT inhibitor VIII displays good selectivity against a panel of 70 other kinases with micromolar inhibition against some kinases, for example, calcium/calmodulin-dependent protein kinase 1 and smooth muscle myosin light-chain kinase.
Hodoodo Cat#: H407161
Name: AKT inhibitor VIII
CAS#: 612847-09-3
Chemical Formula: C34H29N7O
Exact Mass: 551.24
Molecular Weight: 551.650
Elemental Analysis: C, 74.03; H, 5.30; N, 17.77; O, 2.90
Synonym: AKT inhibitor VIII; AKT-inhibitor-VIII; AKT inhibitor-8; AKT-inhibitor-8; Akt-I 1,2; Akti-1/2. Sigma-A6730
IUPAC/Chemical Name: 3-[1-[[4-(7-phenyl-3H-imidazo[4,5-g]quinoxalin-6-yl)phenyl]methyl]piperidin-4-yl]-1H-benzimidazol-2-one
InChi Key: BIWGYFZAEWGBAL-UHFFFAOYSA-N
InChi Code: InChI=1S/C34H29N7O/c42-34-39-26-8-4-5-9-31(26)41(34)25-14-16-40(17-15-25)20-22-10-12-24(13-11-22)33-32(23-6-2-1-3-7-23)37-29-18-27-28(36-21-35-27)19-30(29)38-33/h1-13,18-19,21,25H,14-17,20H2,(H,35,36)(H,39,42)
SMILES Code: O=C1N(C2CCN(CC3=CC=C(C4=NC5=CC6=C(N=CN6)C=C5N=C4C7=CC=CC=C7)C=C3)CC2)C8=CC=CC=C8N1
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).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | AKT inhibitor VIII (AKTi-1/2) inhibits Akt1, Akt2, and Akt3 activity with IC50s of 58 nM, 210 nM, and 2119 nM, respectively. |
| In vitro activity: | The CCK-8 assay shown that combination of ART and AKT inhibitor VIII suppressed more growth of UMRC-2 (Fig. 4A) and CAKI-2 (Fig. 4B) cells than without of AKT inhibitor VIII. Furthermore, colony formation assay shown that combination of ART and AKT inhibitor VIII suppressed more growth of UMRC-2 (Fig. 4C) and CAKI-2 (Fig. 4D) cells than without of AKT inhibitor VIII. In addition, a transwell assay was performed to evaluate the effect of ART with AKT inhibitor VIII on ccRCC cell migration and invasion. Combination of ART and AKT inhibitor VIII enhanced the inhibitory effects of ART on cell migration (Fig. 5A and B) and invasion (Fig. 5C and D). Reference: Biomed Pharmacother. 2019 Oct;118:109383. https://pubmed.ncbi.nlm.nih.gov/31545251/ |
| In vivo activity: | This study hypothesized that inhibitors of the PI3K-Akt-mTOR pathway should inhibit HA synthesis. By adding inhibitors, this study was then able to show that treatment of fro/fro mouse fibroblasts with Akt inhibitor VIII inhibited elevated expression and phosphorylation of Akt (Fig. 6, A and B), and that both Akt inhibitor VIII (5 μm) and PI 3-kinase inhibitors LY294002 (25 μm) and wortmannin (5 μm) were able to reduce HA secretion (Fig. 6C). Reference: J Biol Chem. 2012 Apr 20; 287(17): 13620–13632. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3340193/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 16.8 | 30.51 | |
| DMF | 16.6 | 30.09 | |
| DMF:PBS (pH 7.2) (1:4) | 0.2 | 0.36 |
The following data is based on the product molecular weight 551.65 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. Yu C, Sun P, Zhou Y, Shen B, Zhou M, Wu L, Kong M. Inhibition of AKT enhances the anti-cancer effects of Artemisinin in clear cell renal cell carcinoma. Biomed Pharmacother. 2019 Oct;118:109383. doi: 10.1016/j.biopha.2019.109383. Epub 2019 Aug 30. PMID: 31545251. 2. Mousset CM, Hobo W, Ji Y, Fredrix H, De Giorgi V, Allison RD, Kester MGD, Falkenburg JHF, Schaap NPM, Jansen JH, Gattinoni L, Dolstra H, van der Waart AB. Ex vivo AKT-inhibition facilitates generation of polyfunctional stem cell memory-like CD8+ T cells for adoptive immunotherapy. Oncoimmunology. 2018 Aug 6;7(10):e1488565. doi: 10.1080/2162402X.2018.1488565. PMID: 30288356; PMCID: PMC6169586. 3. Pentassuglia L, Heim P, Lebboukh S, Morandi C, Xu L, Brink M. Neuregulin-1β promotes glucose uptake via PI3K/Akt in neonatal rat cardiomyocytes. Am J Physiol Endocrinol Metab. 2016 May 1;310(9):E782-94. doi: 10.1152/ajpendo.00259.2015. Epub 2016 Mar 15. PMID: 26979522. 4. Qin J, Berdyshev E, Poirer C, Schwartz NB, Dawson G. Neutral sphingomyelinase 2 deficiency increases hyaluronan synthesis by up-regulation of Hyaluronan synthase 2 through decreased ceramide production and activation of Akt. J Biol Chem. 2012 Apr 20;287(17):13620-32. doi: 10.1074/jbc.M111.304857. Epub 2012 Mar 1. PMID: 22383528; PMCID: PMC3340193. |
| In vitro protocol: | 1. Yu C, Sun P, Zhou Y, Shen B, Zhou M, Wu L, Kong M. Inhibition of AKT enhances the anti-cancer effects of Artemisinin in clear cell renal cell carcinoma. Biomed Pharmacother. 2019 Oct;118:109383. doi: 10.1016/j.biopha.2019.109383. Epub 2019 Aug 30. PMID: 31545251. 2. Mousset CM, Hobo W, Ji Y, Fredrix H, De Giorgi V, Allison RD, Kester MGD, Falkenburg JHF, Schaap NPM, Jansen JH, Gattinoni L, Dolstra H, van der Waart AB. Ex vivo AKT-inhibition facilitates generation of polyfunctional stem cell memory-like CD8+ T cells for adoptive immunotherapy. Oncoimmunology. 2018 Aug 6;7(10):e1488565. doi: 10.1080/2162402X.2018.1488565. PMID: 30288356; PMCID: PMC6169586. |
| In vivo protocol: | 1. Pentassuglia L, Heim P, Lebboukh S, Morandi C, Xu L, Brink M. Neuregulin-1β promotes glucose uptake via PI3K/Akt in neonatal rat cardiomyocytes. Am J Physiol Endocrinol Metab. 2016 May 1;310(9):E782-94. doi: 10.1152/ajpendo.00259.2015. Epub 2016 Mar 15. PMID: 26979522. 2. Qin J, Berdyshev E, Poirer C, Schwartz NB, Dawson G. Neutral sphingomyelinase 2 deficiency increases hyaluronan synthesis by up-regulation of Hyaluronan synthase 2 through decreased ceramide production and activation of Akt. J Biol Chem. 2012 Apr 20;287(17):13620-32. doi: 10.1074/jbc.M111.304857. Epub 2012 Mar 1. PMID: 22383528; PMCID: PMC3340193. |
1: Morishita S, Tomita K, Ono T, Murakoshi M, Saito K, Sugiyama K, Nishino H, Kato H. Lactoferrin attenuates fatty acid-induced lipotoxicity via Akt signaling in hepatocarcinoma cells. Biochem Cell Biol. 2015 Jul 28:1-8. [Epub ahead of print] PubMed PMID: 26335364.
2: Myers AL, Lin L, Nancarrow DJ, Wang Z, Ferrer-Torres D, Thomas DG, Orringer MB, Lin J, Reddy RM, Beer DG, Chang AC. IGFBP2 modulates the chemoresistant phenotype in esophageal adenocarcinoma. Oncotarget. 2015 Jul 17. [Epub ahead of print] PubMed PMID: 26317790.
3: Xing W, Guo W, Zou CH, Fu TT, Li XY, Zhu M, Qi JH, Song J, Dong CH, Li Z, Xiao Y, Yuan PS, Huang H, Xu X. Acemannan accelerates cell proliferation and skin wound healing through AKT/mTOR signaling pathway. J Dermatol Sci. 2015 Aug;79(2):101-9. doi: 10.1016/j.jdermsci.2015.03.016. Epub 2015 Apr 1. PubMed PMID: 26049685.
4: Zheng S, Yang Y, Song R, Yang X, Liu H, Ma Q, Yang L, Meng R, Tao T, Wang S, He J. Ang-(1-7) promotes the migration and invasion of human renal cell carcinoma cells via Mas-mediated AKT signaling pathway. Biochem Biophys Res Commun. 2015 May 1;460(2):333-40. doi: 10.1016/j.bbrc.2015.03.035. Epub 2015 Mar 14. PubMed PMID: 25783053.
5: Halacli SO, Dogan AL. FOXP1 regulation via the PI3K/Akt/p70S6K signaling pathway in breast cancer cells. Oncol Lett. 2015 Mar;9(3):1482-1488. Epub 2015 Jan 16. PubMed PMID: 25663935; PubMed Central PMCID: PMC4315073.
6: van der Waart AB, van de Weem NM, Maas F, Kramer CS, Kester MG, Falkenburg JH, Schaap N, Jansen JH, van der Voort R, Gattinoni L, Hobo W, Dolstra H. Inhibition of Akt signaling promotes the generation of superior tumor-reactive T cells for adoptive immunotherapy. Blood. 2014 Nov 27;124(23):3490-500. doi: 10.1182/blood-2014-05-578583. Epub 2014 Oct 21. PubMed PMID: 25336630; PubMed Central PMCID: PMC4246043.
7: Zhu L, Derijard B, Chakrabandhu K, Wang BS, Chen HZ, Hueber AO. Synergism of PI3K/Akt inhibition and Fas activation on colon cancer cell death. Cancer Lett. 2014 Nov 28;354(2):355-64. doi: 10.1016/j.canlet.2014.08.038. Epub 2014 Sep 6. PubMed PMID: 25199763.
8: Liu Q, Qiu J, Liang M, Golinski J, van Leyen K, Jung JE, You Z, Lo EH, Degterev A, Whalen MJ. Akt and mTOR mediate programmed necrosis in neurons. Cell Death Dis. 2014 Feb 27;5:e1084. doi: 10.1038/cddis.2014.69. PubMed PMID: 24577082; PubMed Central PMCID: PMC3944276.
9: Choi J, Jo M, Lee E, Choi D. AKT is involved in granulosa cell autophagy regulation via mTOR signaling during rat follicular development and atresia. Reproduction. 2013 Nov 20;147(1):73-80. doi: 10.1530/REP-13-0386. Print 2014 Jan. PubMed PMID: 24131573.
10: Jang EJ, Seok YM, Arterburn JB, Olatunji LA, Kim IK. GPER-1 agonist G1 induces vasorelaxation through activation of epidermal growth factor receptor-dependent signalling pathway. J Pharm Pharmacol. 2013 Oct;65(10):1488-99. doi: 10.1111/jphp.12113. Epub 2013 Aug 6. PubMed PMID: 24028616.
11: Wilson C, Contreras-Ferrat A, Venegas N, Osorio-Fuentealba C, Pávez M, Montoya K, Durán J, Maass R, Lavandero S, Estrada M. Testosterone increases GLUT4-dependent glucose uptake in cardiomyocytes. J Cell Physiol. 2013 Dec;228(12):2399-407. doi: 10.1002/jcp.24413. PubMed PMID: 23757167.
12: Kumar A, Purohit R. Cancer associated E17K mutation causes rapid conformational drift in AKT1 pleckstrin homology (PH) domain. PLoS One. 2013 May 31;8(5):e64364. doi: 10.1371/journal.pone.0064364. Print 2013. PubMed PMID: 23741320; PubMed Central PMCID: PMC3669323.
13: Huang J, Ledford KJ, Pitkin WB, Russo L, Najjar SM, Siragy HM. Targeted deletion of murine CEACAM 1 activates PI3K-Akt signaling and contributes to the expression of (Pro)renin receptor via CREB family and NF-κB transcription factors. Hypertension. 2013 Aug;62(2):317-23. doi: 10.1161/HYPERTENSIONAHA.113.01324. Epub 2013 Jun 3. PubMed PMID: 23734002; PubMed Central PMCID: PMC3793251.
14: Tao Y, Guo Y, Liu W, Zhang J, Li X, Shen L, Ru Y, Xue Y, Zheng J, Liu X, Zhang J, Yao L. AKT inhibitor suppresses hyperthermia-induced Ndrg2 phosphorylation in gastric cancer cells. Braz J Med Biol Res. 2013 Apr;46(4):394-404. Epub 2013 Apr 5. PubMed PMID: 23558861; PubMed Central PMCID: PMC3854405.
15: Wang H, Zhou X, Huang J, Mu N, Guo Z, Wen Q, Wang R, Chen S, Feng ZP, Zheng W. The role of Akt/FoxO3a in the protective effect of venlafaxine against corticosterone-induced cell death in PC12 cells. Psychopharmacology (Berl). 2013 Jul;228(1):129-41. doi: 10.1007/s00213-013-3017-9. Epub 2013 Mar 15. PubMed PMID: 23494228.
16: Basualto-Alarcón C, Jorquera G, Altamirano F, Jaimovich E, Estrada M. Testosterone signals through mTOR and androgen receptor to induce muscle hypertrophy. Med Sci Sports Exerc. 2013 Sep;45(9):1712-20. doi: 10.1249/MSS.0b013e31828cf5f3. PubMed PMID: 23470307.
17: Fabian AK, März A, Neimanis S, Biondi RM, Kozany C, Hausch F. InterAKTions with FKBPs--mutational and pharmacological exploration. PLoS One. 2013;8(2):e57508. doi: 10.1371/journal.pone.0057508. Epub 2013 Feb 28. PubMed PMID: 23469007; PubMed Central PMCID: PMC3585324.
18: Park TY, Baik EJ, Lee SH. Prostaglandin E₂-induced intercellular adhesion molecule-1 expression is mediated by cAMP/Epac signalling modules in bEnd.3 brain endothelial cells. Br J Pharmacol. 2013 Jun;169(3):604-18. doi: 10.1111/bph.12103. PubMed PMID: 23317035; PubMed Central PMCID: PMC3682708.
19: Jang EJ, Seok YM, Lee JI, Cho HM, Sohn UD, Kim IK. 3',4'-Dimethoxythioflavone induces endothelium-dependent vasorelaxation through activation of epidermal growth factor receptor. Naunyn Schmiedebergs Arch Pharmacol. 2013 Apr;386(4):339-50. doi: 10.1007/s00210-012-0818-z. Epub 2012 Dec 12. PubMed PMID: 23232926.
20: Zhong Z, Dang Y, Yuan X, Guo W, Li Y, Tan W, Cui J, Lu J, Zhang Q, Chen X, Wang Y. Furanodiene, a natural product, inhibits breast cancer growth both in vitro and in vivo. Cell Physiol Biochem. 2012;30(3):778-90. doi: 10.1159/000341457. Epub 2012 Aug 2. PubMed PMID: 22854281.
