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AKT inhibitor CAS: 1004990-28-6

Category: Inhibitors
Product Name: AKT inhibitor
Cat No: I000086
CAS No: 1004990-28-6
Molecular Formula: C20H22F2N6O
Molecular Weight: 400.43
SMILES: O=C(NC[C@]1(N)CN(C2=C3C(NC=C3CC)=NC=N2)CC1)C4=CC=C(F)C=C4F
InChI: InChI=1S/C20H22F2N6O/c1-2-12-8-24-17-16(12)18(27-11-26-17)28-6-5-20(23,10-28)9-25-19(29)14-4-3-13(21)7-15(14)22/h3-4,7-8,11H,2,5-6,9-10,23H2,1H3,(H,25,29)(H,24,26,27)/t20-/m0/s1
InChIKey: MOZRQQTUYAYCQT-FQEVSTJZSA-N
Solubility: 10 mM in DMSO
Target: Akt
IC50: 0.5 nM (PKBα), 450 nM (PKA) [1] [2]
CAS 1004990-28-6,AKT inhibitor
  • Description

AKT inhibitor is a broadly selective, potent, ATP-competitive Akt inhibitor, displays 900-fold greater selectivity for PKBα (IC50 = 0.5 nM) than PKA (IC50=450 nM).
IC50 value: 0.5 nM (PKBα), 450 nM (PKA) [1] [2]
Target: Akt
In vitro: AKT inhibitor binds deeply into the active pocket of PKBα, creating favorably hydrophobic interactions with more residues than that with PKA.[1] AKT inhibitor achieves 900-fold selectivity for Akt over PKA, presumably because of the increased steric demand of the ethyl core substituent being better tolerated in Akt than in PKA. AKT inhibitor is chosen as the most promising molecule to advance to clinical development. [2]
in vivo: AKT inhibitor is well absorbed (F = 54%) in dog pharmacokinetic studies (oral at 2 mg/kg, iv at 1.2 mg/kg), with moderate clearance (11.6 mL/min/kg) and volume of distribution (4.8 L/kg), and a half-life of 4.4 h. AKT inhibitor is subsequently evaluated for modulation of Akt in tumors53 and in multiple in vivo mouse models of antitumor efficacy. AKT inhibitor is active in a PC3 prostate carcinoma xenograft experiment, with 75% TGI observed at 100 mg/kg b.i.d. dosing for 10 days. In a colorectal carcinoma (Colo205) xenograft study, AKT inhibitor produces 60% TGI at 150 mg/kg b.i.d. after 10 days.Most intriguingly, in combination with rapamycin (10 mg/kg, ip), 75 mg/kg b.i.d.(10 days) of 42 resulted in 98% TGI in an additional PC3 prostate carcinomaxenograft study compared to 56%TGIand 66%TGI with 42 and rapamycin as single agents. [2]

  • Spec

Appearance:Solid powder
Purity: > 98%

  • References


1:Akt inhibitor MK-2206 in combination with Bendamustine and Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia: Results from the N1087 Alliance Study. Larsen JT, Shanafelt TD, Leis JF, LaPlant B, Call T, Pettinger A, Hanson C, Erlichman C, Habermann TM, Reeder C, Nikcevich D, Bowen D, Conte M, Boysen J, Secreto C, Lesnick C, Tschumper R, Jelinek D, Kay NE, Ding W.Am J Hematol. 2017 Apr 12. doi: 10.1002/ajh.24762. [Epub ahead of print] PMID: 28402581
2:Durable Control of Metastatic AKT1-Mutant WHO Grade 1 Meningothelial Meningioma by the AKT Inhibitor, AZD5363. Weller M, Roth P, Sahm F, Burghardt I, Schuknecht B, Rushing EJ, Regli L, Lindemann JP, von Deimling A.J Natl Cancer Inst. 2017 Mar 1;109(3):1-4. doi: 10.1093/jnci/djw320. PMID: 28376212
3:TCN, an AKT inhibitor, exhibits potent antitumor activity and enhances radiosensitivity in hypoxic esophageal squamous cell carcinoma in vitro and in vivo. Guo Q, He J, Shen F, Zhang W, Yang X, Zhang C, Zhang Q, Huang JX, Wu ZD, Sun XC, Dai SB.Oncol Lett. 2017 Feb;13(2):949-954. doi: 10.3892/ol.2016.5515. Epub 2016 Dec 20. PMID: 28356983 Free PMC Article
4:The allosteric AKT inhibitor MK2206 shows a synergistic interaction with chemotherapy and radiotherapy in glioblastoma spheroid cultures. Narayan RS, Fedrigo CA, Brands E, Dik R, Stalpers LJ, Baumert BG, Slotman BJ, Westerman BA, Peters GJ, Sminia P.BMC Cancer. 2017 Mar 21;17(1):204. doi: 10.1186/s12885-017-3193-9. PMID: 28320338 Free PMC Article
5:Curcuminoid EF24 enhances the anti-tumour activity of Akt inhibitor MK-2206 through ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction in gastric cancer. Chen X, Dai X, Zou P, Chen W, Rajamanickam V, Feng C, Zhuge W, Qiu C, Ye Q, Zhang X, Liang G.Br J Pharmacol. 2017 May;174(10):1131-1146. doi: 10.1111/bph.13765. Epub 2017 Apr 6. PMID: 28255993
6:In-vitro and in-vivo combined effect of ARQ 092, an AKT inhibitor, with ARQ 087, a FGFR inhibitor. Yu Y, Hall T, Eathiraj S, Wick MJ, Schwartz B, Abbadessa G.Anticancer Drugs. 2017 Jun;28(5):503-513. doi: 10.1097/CAD.0000000000000486. PMID: 28240679 Free PMC Article
7:ProCAID: a phase I clinical trial to combine the AKT inhibitor AZD5363 with docetaxel and prednisolone chemotherapy for metastatic castration resistant prostate cancer. Crabb SJ, Birtle AJ, Martin K, Downs N, Ratcliffe I, Maishman T, Ellis M, Griffiths G, Thompson S, Ksiazek L, Khoo V, Jones RJ.Invest New Drugs. 2017 Feb 1. doi: 10.1007/s10637-017-0433-4. [Epub ahead of print] PMID: 28144789
8:The allosteric AKT inhibitor, MK2206, decreases tumor growth and invasion in patient derived xenografts of endometrial cancer. Winder A, Unno K, Yu Y, Lurain J, Kim JJ.Cancer Biol Ther. 2017 Jan 23:0. doi: 10.1080/15384047.2017.1281496. [Epub ahead of print] PMID: 28112582
9:A First-in-Human Phase I Study of the ATP-Competitive AKT Inhibitor Ipatasertib Demonstrates Robust and Safe Targeting of AKT in Patients with Solid Tumors. Saura C, Roda D, Roselló S, Oliveira M, Macarulla T, Pérez-Fidalgo JA, Morales-Barrera R, Sanchis-García JM, Musib L, Budha N, Zhu J, Nannini M, Chan WY, Sanabria Bohórquez SM, Meng RD, Lin K, Yan Y, Patel P, Baselga J, Tabernero J, Cervantes A.Cancer Discov. 2017 Jan;7(1):102-113. doi: 10.1158/2159-8290.CD-16-0512. Epub 2016 Nov 21. PMID: 27872130
10:A phase IIa study of afuresertib, an oral pan-AKT inhibitor, in patients with Langerhans cell histiocytosis. Arceci RJ, Allen CE, Dunkel IJ, Jacobsen E, Whitlock J, Vassallo R, Morris SR, Portnoy A, Reedy BA, Smith DA, Noble R, Murnane A, Cornfeld M, Rodriguez-Galindo C, Heaney ML, McClain K, Vaiselbuh S.Pediatr Blood Cancer. 2017 May;64(5). doi: 10.1002/pbc.26325. Epub 2016 Nov 2. PMID: 27804235


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