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Purity: ≥98%
GSK2879552 (GSK-2879552) is a novel, potent and orally bioavailable, irreversible inhibitor of lysine specific demethylase 1 (LSD1) with potential anticancer activity. Epigenetic dysregulation has emerged as an important mechanism in cancer. Alterations in epigenetic machinery have become a major focus for targeted therapies. A proliferation screen of cell lines representing a number of tumor types indicated that small cell lung carcinoma (SCLC) is sensitive to LSD1 inhibition. The subset of SCLC lines and primary samples that undergo growth inhibition in response to GSK2879552 exhibit DNA hypomethylation of a signature set of probes, suggesting this may be used as a predictive biomarker of activity.
| ln Vitro |
GSK2879552 reduces the characteristics of stem cells, causes the differentiation of cells resistant to sorafenib, and inhibits the activity of KDM1A histone demethylase. In cells resistant to sorafenib, GSK2879552 downregulates β-catenin signaling activity and suppresses the transcription of Wnt antagonists [1].
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| ln Vivo |
In mice containing SCLC xenografts, GSK2879552 (1.5 mg/kg, po) therapy showed tumor growth reduction [2].
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| Cell Assay |
Cell Proliferation Assay[2].
Cell Types: 9/28 small cell lung carcinoma (SCLC) lines and 20/29 AML lines. Tested Concentrations: 0-10000 nM. Incubation Duration: 6 days. Experimental Results: Inhibited cell proliferation. RT-PCR [1]. Cell Types: Resistant HCC cells (PLC/PRF/5 and Huh7). Tested Concentrations: 0, 1, 2 μM. Incubation Duration: 24 h. Experimental Results: Displayed decreased mRNA expression levels of stem cell markers, such as Lgr5, Sox9, Nanog and CD90, and elevated mRNA expression levels of differentiation markers Alb and Hnf4. |
| Animal Protocol |
Animal/Disease Models: NCI-H526 and NCI-H1417 xenografts[2].
Doses: 1.5 mg/kg. Route of Administration: PO daily for 25-35 days. Experimental Results: There was 57% and 83% tumor growth inhibition (TGI) in NCI- H526 and NCI-H1417 tumor bearing mice respectively. NCI-H510 and NCI-H69 tumor bearing mice also demonstrated partial TGI (38% and 49% respectively) in response to GSK2879552, while no significant TGI was observed for SHP77 bearing mice. |
| References |
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| Additional Infomation |
GSK2879552 is a member of the class of piperidines that is piperidine substituted by (4-carboxyphenyl)methyl and {[(1R,2S)-2-phenylcyclopropyl]amino}methyl groups at positions 1 and 4, respectively. It is a potent and irreversible inhibitor of lysine specific demethylase 1 (LSD1, also known as KDM1A). It was under clinical investigation for the treatment of acute myeloid leukaemia and small cell lung carcinoma. It has a role as an EC 1.14.99.66 (lysine-specific histone demethylase 1A) inhibitor and an antineoplastic agent. It is a member of benzoic acids, a monocarboxylic acid, a member of piperidines, a member of cyclopropanes, a tertiary amino compound, a secondary amino compound and a member of benzenes.
LSD1 Inhibitor GSK2879552 is an orally available, irreversible, inhibitor of lysine specific demethylase 1 (LSD1), with potential antineoplastic activity. Upon administration, GSK2879552 binds to and inhibits LSD1, a demethylase that suppresses the expression of target genes by converting the dimethylated form of lysine at position 4 of histone H3 (H3K4) to mono- and unmethylated H3K4. LSD1 inhibition enhances H3K4 methylation and increases the expression of tumor-suppressor genes. This may lead to an inhibition of cell growth in LSD1-overexpressing tumor cells. LSD1, overexpressed in certain tumor cells, plays a key role in tumor cell growth and survival. |
| Molecular Formula |
C23H30CL2N2O2
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|---|---|
| Molecular Weight |
437.4025
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| Exact Mass |
364.215
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| CAS # |
1401966-69-5
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| Related CAS # |
GSK2879552 dihydrochloride;1902123-72-1
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| PubChem CID |
66571643
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| Appearance |
White to off-white solid powder
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| LogP |
4.071
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
27
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| Complexity |
475
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1CN(CCC1CN[C@@H]2C[C@H]2C3=CC=CC=C3)CC4=CC=C(C=C4)C(=O)O
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| InChi Key |
LRULVYSBRWUVGR-FCHUYYIVSA-N
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| InChi Code |
InChI=1S/C23H28N2O2/c26-23(27)20-8-6-18(7-9-20)16-25-12-10-17(11-13-25)15-24-22-14-21(22)19-4-2-1-3-5-19/h1-9,17,21-22,24H,10-16H2,(H,26,27)/t21-,22+/m0/s1
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| Chemical Name |
4-((4-((((1R,2S)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoic acid
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| Synonyms |
GSK-2879552; GSK2879552; GSK 2879552.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~25 mg/mL (~68.59 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (7.54 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.75 mg/mL (7.54 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.75 mg/mL (7.54 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2862 mL | 11.4312 mL | 22.8624 mL | |
| 5 mM | 0.4572 mL | 2.2862 mL | 4.5725 mL | |
| 10 mM | 0.2286 mL | 1.1431 mL | 2.2862 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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