WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H205481
CAS#: 1047634-65-0 (free base)
Description: Uprosertib, also known as GSK2141795 and GSK795, is an orally bioavailable inhibitor of the serine/threonine protein kinase Akt (protein kinase B) with potential antineoplastic activity. Akt inhibitor GSK2141795 binds to and inhibits the activity of Akt, which may result in inhibition of the PI3K/Akt signaling pathway and tumor cell proliferation and the induction of tumor cell apoptosis. Activation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents.
Hodoodo Cat#: H205481
Name: Uprosertib
CAS#: 1047634-65-0 (free base)
Chemical Formula: C18H16Cl2F2N4O2
Exact Mass: 428.06
Molecular Weight: 429.250
Elemental Analysis: C, 50.37; H, 3.76; Cl, 16.52; F, 8.85; N, 13.05; O, 7.45
Related CAS #: 1047635-80-2 (HCl) 1047634-65-0 (free base)
Synonym: GSK2141795, GSK2141795, GSK 2141795, GSK795, GSK795, GSK 795, Uprosertib
IUPAC/Chemical Name: N-((S)-1-amino-3-(3,4-difluorophenyl)propan-2-yl)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)furan-2-carboxamide
InChi Key: AXTAPYRUEKNRBA-JTQLQIEISA-N
InChi Code: InChI=1S/C18H16Cl2F2N4O2/c1-26-16(12(19)8-24-26)11-6-15(28-17(11)20)18(27)25-10(7-23)4-9-2-3-13(21)14(22)5-9/h2-3,5-6,8,10H,4,7,23H2,1H3,(H,25,27)/t10-/m0/s1
SMILES Code: O=C(C1=CC(C2=C(Cl)C=NN2C)=C(Cl)O1)N[C@@H](CC3=CC=C(F)C(F)=C3)CN
Appearance: White to off-white 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: Related CAS# 1047634-65-0 (GSK-2141795); 1047635-80-2 (GSK-2141795 HCl salt)
Biological target: | Uprosertib (GSK2141795) is a pan-Akt inhibitor with IC50 values of 180/328/38 nM for Akt1/Akt2/Akt3, respectively. |
In vitro activity: | Treatment of DMS114-R cell line with GSK2141795 alone resulted in a significant decrease in cell viability with dose as little as 100nmol/L. Though, increasing doses reduced cell viability further, with 80% decrease noticed at 3µmol/L concentration of GSK2141795 (Figure 4A). Low doses of GSK2141795 had no effect on cell viability in the DMS114 control cell line, while a high dose (3µmol/L) had a mild effect. While the combination of BGJ398 (100nmol/L) with GSK2141795 (100nmol/L) produced a significant reduction in cell viability, this effect was not significant compared to the use of GSK2141795 as a single agent, indicating that treatment of Akt inhibitor alone is sufficient to inhibit the viability of BGJ398 resistant DMS114 cells (Figure 4A). Thus, Akt signaling pathway is highly activated in the BGJ398 resistant DMS114 cell line and treatment with GSK2141795 inhibits cell viability. Reference: Mol Cancer Ther. 2017 Apr; 16(4): 614–624. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5539948/ |
In vivo activity: | Mice bearing BT474 tumors were dosed orally with either vehicle or GSK2141795. After 20 days of treatment with 10, 20 and 30 mg/kg of GSK2141795, tumor growth inhibition (TGI) of 28, 57 and 98%, respectively, was observed relative to vehicle control (Figure 6A). Minimal body weight loss of 3–8% was reported on day 6 of dosing which recovered by the end of study (data not shown). Reference: PLoS One. 2014; 9(6): e100880. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076210/ |
Solvent | Max Conc. mg/mL | Max Conc. mM | |
---|---|---|---|
Solubility | |||
DMSO | 45.3 | 105.60 | |
DMF | 1.0 | 2.33 | |
Ethanol | 85.0 | 198.02 |
The following data is based on the product molecular weight 429.25 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. Datta J, Damodaran S, Parks H, Ocrainiciuc C, Miya J, Yu L, Gardner EP, Samorodnitsky E, Wing MR, Bhatt D, Hays J, Reeser JW, Roychowdhury S. Akt Activation Mediates Acquired Resistance to Fibroblast Growth Factor Receptor Inhibitor BGJ398. Mol Cancer Ther. 2017 Apr;16(4):614-624. doi: 10.1158/1535-7163.MCT-15-1010. Epub 2017 Mar 2. PMID: 28255027; PMCID: PMC5539948. 2. Dumble M, Crouthamel MC, Zhang SY, Schaber M, Levy D, Robell K, Liu Q, Figueroa DJ, Minthorn EA, Seefeld MA, Rouse MB, Rabindran SK, Heerding DA, Kumar R. Discovery of novel AKT inhibitors with enhanced anti-tumor effects in combination with the MEK inhibitor. PLoS One. 2014 Jun 30;9(6):e100880. doi: 10.1371/journal.pone.0100880. PMID: 24978597; PMCID: PMC4076210. 4. Sohn SH, Sul HJ, Kim B, Kim HS, Kim BJ, Lim H, Kang HS, Soh JS, Kim KC, Cho JW, Seo J, Koh Y, Zang DY. RNF43 and PWWP2B inhibit cancer cell proliferation and are predictive or prognostic biomarker for FDA-approved drugs in patients with advanced gastric cancer. J Cancer. 2021 Jun 1;12(15):4616-4625. doi: 10.7150/jca.56014. PMID: 34149925; PMCID: PMC8210561. |
In vitro protocol: | 1. Datta J, Damodaran S, Parks H, Ocrainiciuc C, Miya J, Yu L, Gardner EP, Samorodnitsky E, Wing MR, Bhatt D, Hays J, Reeser JW, Roychowdhury S. Akt Activation Mediates Acquired Resistance to Fibroblast Growth Factor Receptor Inhibitor BGJ398. Mol Cancer Ther. 2017 Apr;16(4):614-624. doi: 10.1158/1535-7163.MCT-15-1010. Epub 2017 Mar 2. PMID: 28255027; PMCID: PMC5539948. 2. Dumble M, Crouthamel MC, Zhang SY, Schaber M, Levy D, Robell K, Liu Q, Figueroa DJ, Minthorn EA, Seefeld MA, Rouse MB, Rabindran SK, Heerding DA, Kumar R. Discovery of novel AKT inhibitors with enhanced anti-tumor effects in combination with the MEK inhibitor. PLoS One. 2014 Jun 30;9(6):e100880. doi: 10.1371/journal.pone.0100880. PMID: 24978597; PMCID: PMC4076210. |
In vivo protocol: | 1. Dumble M, Crouthamel MC, Zhang SY, Schaber M, Levy D, Robell K, Liu Q, Figueroa DJ, Minthorn EA, Seefeld MA, Rouse MB, Rabindran SK, Heerding DA, Kumar R. Discovery of novel AKT inhibitors with enhanced anti-tumor effects in combination with the MEK inhibitor. PLoS One. 2014 Jun 30;9(6):e100880. doi: 10.1371/journal.pone.0100880. PMID: 24978597; PMCID: PMC4076210. 2. Sohn SH, Sul HJ, Kim B, Kim HS, Kim BJ, Lim H, Kang HS, Soh JS, Kim KC, Cho JW, Seo J, Koh Y, Zang DY. RNF43 and PWWP2B inhibit cancer cell proliferation and are predictive or prognostic biomarker for FDA-approved drugs in patients with advanced gastric cancer. J Cancer. 2021 Jun 1;12(15):4616-4625. doi: 10.7150/jca.56014. PMID: 34149925; PMCID: PMC8210561. |
1: Dumble M, Crouthamel MC, Zhang SY, Schaber M, Levy D, Robell K, Liu Q, Figueroa DJ, Minthorn EA, Seefeld MA, Rouse MB, Rabindran SK, Heerding DA, Kumar R. Discovery of Novel AKT Inhibitors with Enhanced Anti-Tumor Effects in Combination with the MEK Inhibitor. PLoS One. 2014 Jun 30;9(6):e100880. doi: 10.1371/journal.pone.0100880. eCollection 2014. PubMed PMID: 24978597; PubMed Central PMCID: PMC4076210.
2: Pachl F, Plattner P, Ruprecht B, Médard G, Sewald N, Kuster B. Characterization of a chemical affinity probe targeting Akt kinases. J Proteome Res. 2013 Aug 2;12(8):3792-800. doi: 10.1021/pr400455j. Epub 2013 Jul 3. PubMed PMID: 23795919.
3: Pal SK, Reckamp K, Yu H, Figlin RA. Akt inhibitors in clinical development for the treatment of cancer. Expert Opin Investig Drugs. 2010 Nov;19(11):1355-66. doi: 10.1517/13543784.2010.520701. Epub 2010 Sep 16. Review. PubMed PMID: 20846000; PubMed Central PMCID: PMC3244346.