GSK239512
Based on 1 Customer Validation
GSK239512 is a blood-brain barrier-permeable, orally active H3 receptor antagonist, with a human pKi ranging from <5.5 to 9.92 and a murine pKi ranging from 9.44 to 9.83. GSK239512 modulates cholinergic and monoaminergic neurotransmission, blocks the inhibitory feedback of H3 receptors, and increases the release of pro-cognitive neurotransmitters. GSK239512 induces oligodendrocyte precursor cell differentiation and restores myelin gene expression at the cellular level. GSK239512 reverses Scopolamine (HY-N0296)-induced memory deficits and improves recognition memory in animal models. GSK239512 can be used in research related to Alzheimer's disease, chronic traumatic encephalopathy, relapsing-remitting multiple sclerosis, and schizophrenia.
For research use only. We do not sell to patients.
- Purity: 99.09%
- CAS No.: 720691-69-0
- Formula: C23H27N3O2
- Molecular Weight:377.48
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Storage:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
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All Histamine Receptor Isoforms
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Biological Activity
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rat H3 receptor <5.5-9.92 (pKi) |
human H3 receptor 9.44-9.83 (pKi) |
GSK239512 (10 μM; 5 days) promotes the differentiation of primary rat oligodendrocyte precursor cells into mature oligodendrocytes[2][3].
GSK239512 potently binds to human and rat H3 receptors in native cerebral cortex membranes and recombinant HEK-293 cells, with pKi values ranging from 9.44 to 9.92, and exhibits over 1000-fold selectivity over other protein targets[6].
GSK239512 exhibits favorable in vitro druggability profiles, including extremely weak hERG inhibitory effect, no cytochrome P450 inhibitory activity, high water solubility, moderate binding affinity to human serum albumin, and good metabolic stability in rat and human liver microsomes[6].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Primary rat oligodendrocyte progenitor cells (OPC)
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Concentration:10 μM
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Incubation Time:5 days
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Result:Significantly increased MBP staining by approximately 50% in primary rat oligodendrocyte progenitor cells and promoted their differentiation into mature oligodendrocytes.
| Species | Dose | Route | CLblood | Vss | Cmax | T1/2 | Tmax | Bioavailability |
|---|---|---|---|---|---|---|---|---|
| Rat[6] | 1 mg/kg | i.v. | 39 mL/min/kg | 3.1 L/kg | 0.671 μM | 1.2 h | / | / |
| Rat[6] | 2 mg/kg | p.o. | / | / | 0.348 μM | 2.1 h | 1.0 (range 0.5-1.5) h | 51 % |
| Dog[6] | 0.5 mg/kg | i.v. | 22 mL/min/kg | 2.8 L/kg | 0.393 μM | 1.7 h | / | / |
| Dog[6] | 0.5 mg/kg | p.o. | / | / | 0.120 μM | 1.8 h | 0.7 h | 33 % |
| Monkey[6] | 0.5 mg/kg | i.v. | 28 mL/min/kg | 3.2 L/kg | 0.383 μM | 1.7 h | / | / |
| Monkey[6] | 0.5 mg/kg | p.o. | / | / | 0.145 μM | 1.7 h | 1.3 (range 1.0-1.3) h | 55 % |
GSK239512 (0.3-3 mg/kg; p.o.) significantly reverses scopolamine (HY-N0296)-induced cognitive impairment in rats at doses of 1 mg/kg and 3 mg/kg (p.o.)[6].
GSK239512 (0.04-3 mg/kg; p.o.) achieves significant occupancy of histamine H3 receptors in the rat cortex, with an estimated EC50 value of 0.015 μM; it also significantly reverses polydipsia induced by H3 agonists in rats, with an ED50 of 0.04 mg/kg[6].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Tau58.4 homozygous (3-4 month old male, 22-30 g, overexpressing P301S 0N4R human tau on C57BL/6 background, 42 closed-head repeated mild traumatic brain impacts)[2]
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Dosage:10 mg/kg
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Administration:p.o.; twice daily; 1 month
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Result:Restored optic nerve tract (ONT) gene expression of Mbp and Gpr37 to sham levels.
Increased Mog gene expression in ONT compared to untreated rmTBI mice.
Increased proportion of OLIG2+ nuclei in ONT lesions compared to untreated rmTBI lesions.
Failed to reduce presence of demyelinated ON lesions (measured by Luxol fast blue staining).
Did not decrease CD3+ T-cell counts in the ON.
Did not reduce ON cellularity.
Had no effect on tauopathy, neuronal staining, or myeloid cell infiltration into white matter.
Increased *Mog* expression in cortex to sham levels, which was not significantly different from untreated rmTBI mice.
Did not influence myelin in the corpus callosum or optic tract demyelination.
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Animal Model:Sprague-Dawley (male)[6]
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Dosage:0.3 mg/kg; 1 mg/kg; 3 mg/kg
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Administration:p.o.
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Result:Dose-dependently reversed Scopolamine-induced amnesia.
Significantly improved 24-hour recall latency at 1 mg/kg and 3 mg/kg.
Showed latency comparable to untreated control rats at 3 mg/kg.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 720691-69-0
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Appearance Solid
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Molecular Weight 377.48
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Formula C23H27N3O2
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Color White to light yellow
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SMILES
O=C1N(C2=CC=C(OC3=CC=C4CCN(C5CCC5)CCC4=C3)N=C2)CCC1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
DMSO : 5 mg/mL (13.25 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Purity & Documentation
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Data Sheet (279 KB)
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SDS (420 KB)
- English - EN (420 KB)
- Français - FR (420 KB)
- Deutsch - DE (420 KB)
- Norwegian - NO (420 KB)
- Español - ES (420 KB)
- Swedish - SV (420 KB)
- Italian - IT (420 KB)
- Korean - KR (420 KB)
- Portuguese - PT (420 KB)
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Handling Instructions (2659 KB)
References
[1]. Grove RA, et al. A randomized, double-blind, placebo-controlled, 16-week study of the H3 receptor antagonist, GSK239512 as a monotherapy in subjects with mild-to-moderate Alzheimer's disease. Current Alzheimer research. 2014 Jan;11(1):47-58. [Content Brief]
[2]. Cheng H, et al. Tau overexpression exacerbates neuropathology after repeated mild head impacts in male mice. Neurobiol Dis. 2020 Feb;134:104683. [Content Brief]
[3]. Schwartzbach CJ, et al. Lesion remyelinating activity of GSK239512 versus placebo in patients with relapsing-remitting multiple sclerosis: a randomised, single-blind, phase II study. Journal of neurology. 2017 Feb;264(2):304-315. [Content Brief]
[4]. Jarskog LF, et al. A Phase II study of a histamine H₃ receptor antagonist GSK239512 for cognitive impairment in stable schizophrenia subjects on antipsychotic therapy. Schizophrenia research. 2015 May;164(1-3):136-42. [Content Brief]
[5]. Ashworth S, et al. Unexpectedly high affinity of a novel histamine H(3) receptor antagonist, GSK239512, in vivo in human brain, determined using PET. British journal of pharmacology. 2014 Mar;171(5):1241-9. [Content Brief]
[6]. Wilson DM, et al. Identification of clinical candidates from the benzazepine class of histamine H3 receptor antagonists. Bioorganic & medicinal chemistry letters. 2013 Dec 15;23(24):6890-6. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.6491 mL | 13.2457 mL | 26.4915 mL | 66.2287 mL |
| 5 mM | 0.5298 mL | 2.6491 mL | 5.2983 mL | 13.2457 mL | |
| 10 mM | 0.2649 mL | 1.3246 mL | 2.6491 mL | 6.6229 mL |
GSK239512 Related Classifications
HY-106000 Related Classifications
Powered by Bioz
- GSK239512
- 720691-69-0
- GSK 239512
- GSK-239512
- Histamine Receptor
- histamine H3 receptor
- oligodendrocyte progenitor cell
- relapsing-remitting multiple sclerosis
- optic nerve myelin
- schizophrenia
- cholinergic neurotransmission
- chronic traumatic encephalopathy
- mild-to-moderate Alzheimer’s disease
- HEK-293 cells
- monoaminergic neurotransmission
- Inhibitor
- inhibitor
- inhibit