| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
GSK-690 targets lysine-specific demethylase 1 (LSD1, also known as KDM1A), a flavin-dependent monoamine oxidase that demethylates histone H3 at lysine 4 (H3K4) and lysine 9 (H3K9). LSD1 plays a critical role in epigenetic regulation, gene transcription, and cell differentiation. By inhibiting LSD1, GSK-690 alters histone methylation patterns and gene expression programs, promoting differentiation of cancer cells. The compound shows selectivity for LSD1 over MAO-A.
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| ln Vitro |
GSK-690 (1-10μM) acts together with JNJ-26481585 to induce cell death in all four tested RMS cells lines (RD, RH30, RMS13, and TE381.T cells)[2]. GSK690/JNJ-26481585 cotreatment alters the balance between pro- and antiapoptotic proteins with 1 μM GSK690 for RD cells) and 10 μM GSK690 for RH30 cells[2]. GSK690/JNJ-26481585 cotreatment induces caspase-dependent cell death with 1 μM GSK690 for RD cells and 10 μM GSK690 for RH30 cells[2]. The addition of GSK690 further enhances the JNJ-26481585-stimulated G2/M arrest [2]. |
| ln Vivo |
In vivo activity data for GSK-690 are limited in the literature. Based on its in vitro LSD1 inhibition and ability to induce differentiation of leukemic stem cells, it is anticipated to have potential in vivo efficacy in AML and other cancer models. However, specific animal studies detailing its therapeutic effects, dosing, and pharmacokinetics are not extensively documented.
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| Enzyme Assay |
The non-cellular enzyme/receptor binding assay for GSK-690 typically involves measuring LSD1 enzymatic activity using a fluorometric or radiometric assay. Recombinant LSD1 enzyme is incubated with a histone H3 peptide substrate and varying concentrations of GSK-690. Demethylation activity is measured by detecting the production of formaldehyde or by using a coupled enzymatic assay. IC₅₀ and Kd values are calculated from dose-response curves. Selectivity over MAO-A is assessed similarly.
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| Cell Assay |
In vitro cellular assays for GSK-690 typically use AML cell lines or other cancer cell lines to evaluate LSD1 inhibition and differentiation. Cells are treated with various concentrations of GSK-690 for several days. LSD1 activity is assessed by measuring H3K4 and H3K9 methylation levels by Western blotting or mass spectrometry. Cell differentiation is evaluated by flow cytometry using differentiation markers. Cell proliferation is assessed using MTT or cell counting assays. Apoptosis is detected by Annexin V/PI staining.
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| Animal Protocol |
In vivo animal studies for GSK-690 are not extensively documented. Based on its LSD1 inhibitory mechanism and potential in AML, typical study designs would involve mouse models of AML or other cancers. GSK-690 would be administered orally or intraperitoneally. Tumor burden, differentiation markers, and survival rates would be evaluated. Bone marrow and peripheral blood would be analyzed for leukemic cell differentiation and apoptosis.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of GSK-690 are not extensively characterized. As a small molecule inhibitor with molecular weight approximately 500, it is expected to have reasonable oral bioavailability. The compound is likely metabolized in the liver via cytochrome P450 enzymes. Specific PK parameters such as half-life, Cmax, and protein binding are not well documented.
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| Toxicity/Toxicokinetics |
Pharmacokinetic properties of GSK-690 are not extensively characterized. As a small molecule inhibitor with molecular weight approximately 500, it is expected to have reasonable oral bioavailability. The compound is likely metabolized in the liver via cytochrome P450 enzymes. Specific PK parameters such as half-life, Cmax, and protein binding are not well documented.
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| References | |
| Additional Infomation |
GSK-690 is a research-grade compound intended for laboratory use only. It is not approved for clinical use as a therapeutic agent. Its primary applications include studying LSD1 biology and epigenetic regulation, investigating the role of LSD1 in cancer and stem cell differentiation, and exploring the therapeutic potential of LSD1 inhibitors in AML and other cancers. The compound is a valuable tool for epigenetic and cancer research.
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| Exact Mass |
405.161
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|---|---|
| Related CAS # |
2101305-84-2
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| PubChem CID |
135397147
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
2
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
29
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| Complexity |
527
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=CC=C(C=C1)C2=C(C=C(C=N2)OC[C@@H]3CCNC3)C4=CC=C(C=C4)C#N.Cl
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| InChi Key |
DBTSJYXXWZFXNJ-FSRHSHDFSA-N
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| InChi Code |
InChI=1S/C24H23N3O.ClH/c1-17-2-6-21(7-3-17)24-23(20-8-4-18(13-25)5-9-20)12-22(15-27-24)28-16-19-10-11-26-14-19;/h2-9,12,15,19,26H,10-11,14,16H2,1H3;1H/t19-;/m1./s1
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| Chemical Name |
4-[2-(4-methylphenyl)-5-[[(3R)-pyrrolidin-3-yl]methoxy]-3-pyridinyl]benzonitrile;hydrochloride
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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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