Radiprodil | RGH-896 | CAS#496054-87-6 | NMDA NR2B antagonist

MedKoo Cat#: 319896 | Name: Radiprodil

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Radiprodil, also known as RGH-896, is an orally active and selective NMDA receptors antagonist which was evaluated as potential treatmen of neuropathic pain associated with diabetic peripheral neuropathy (DPNP). Treatment with radiprodil did not show statistically significant or clinically meaningful reductions in mean daily pain scores, the primary endpoint, compared to placebo for any of the dosages studied. Based on preclinical pharmacology Radiprodil was a potential therapeutic agent in treatment of neuropathic pain and possibly other chronic pain conditions.

Chemical Structure

Radiprodil

CAS#496054-87-6 (free base)

Theoretical Analysis

MedKoo Cat#: 319896

Name: Radiprodil

CAS#: 496054-87-6 (free base)

Chemical Formula: C21H20FN3O4

Exact Mass: 397.1438

Molecular Weight: 397.41

Elemental Analysis: C, 63.47; H, 5.07; F, 4.78; N, 10.57; O, 16.10

Price and Availability

Size	Price	Availability
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 2,150.00	2 Weeks
1g	USD 3,150.00	2 Weeks
2g	USD 5,450.00	2 Weeks

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Related CAS #

496054-87-6 (free base) 1204354-40-4 (dihydrate)

Synonym

RGH-896; RGH896; RGH 896; Radiprodil

IUPAC/Chemical Name

2-(4-((4-Fluorophenyl)methyl)piperidin-1-yl)-2-oxo-N-(2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)acetamide

InChi Key

GKGRZLGAQZPEHO-UHFFFAOYSA-N

InChi Code

InChI=1S/C21H20FN3O4/c22-15-3-1-13(2-4-15)11-14-7-9-25(10-8-14)20(27)19(26)23-16-5-6-17-18(12-16)29-21(28)24-17/h1-6,12,14H,7-11H2,(H,23,26)(H,24,28)

SMILES Code

O=C(NC1=CC=C2NC(OC2=C1)=O)C(N3CCC(CC4=CC=C(F)C=C4)CC3)=O

Appearance

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

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Radiprodil is an antagonist of NR2B subunit-containing NMDA receptors (IC50 = 8 nM). It is selective for NR2B subunit-containing NMDA receptors over NR1 and NR2A subunit-containing NMDA receptors at 15 µM. Radiprodil (10 nM) reduces amyloid β (1-42) (Aβ42) and Aβ40-induced decreases in dendritic spine density in mouse hippocampal CA1 pyramidal neurons. Radiprodil (2 mg/kg) restores novel object-stimulated locomotion in a marmoset model of MPTP-induced Parkinson's disease.

In vitro activity:

Findings from this study suggest that radiprodil may be a valuable therapeutic option for treatment of pediatric epileptic encephalopathies associated with GRIN2B mutations. Reference: Neuropharmacology. 2017 Sep 1;123:322-331. https://pubmed.ncbi.nlm.nih.gov/28533163/

In vivo activity:

Radiprodil/Tozadenant combination treatment significantly improved motor activity in a marmoset model of Parkinson's Disease. This suggests that the use of such an A2A and NR2B antagonist combination (Radiprodil is the NR2B antagonist) could bring significant motor improvement to Parkinson's Disease patients, without inducing the motor complications induced by L-Dopa therapy. Reference: PLoS One. 2017 Aug 30;12(8):e0182887. https://pubmed.ncbi.nlm.nih.gov/28854243/

Preparing Stock Solutions

The following data is based on the product molecular weight 397.41 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. Mullier B, Wolff C, Sands ZA, Ghisdal P, Muglia P, Kaminski RM, André VM. GRIN2B gain of function mutations are sensitive to radiprodil, a negative allosteric modulator of GluN2B-containing NMDA receptors. Neuropharmacology. 2017 Sep 1;123:322-331. doi: 10.1016/j.neuropharm.2017.05.017. Epub 2017 May 19. PMID: 28533163. 2. Michel A, Nicolas JM, Rose S, Jackson M, Colman P, Briône W, Sciberras D, Muglia P, Scheller DK, Citron M, Downey P. Antiparkinsonian effects of the "Radiprodil and Tozadenant" combination in MPTP-treated marmosets. PLoS One. 2017 Aug 30;12(8):e0182887. doi: 10.1371/journal.pone.0182887. PMID: 28854243; PMCID: PMC5576667. 3. Michel A, Downey P, Van Damme X, De Wolf C, Schwarting R, Scheller D. Behavioural Assessment of the A2a/NR2B Combination in the Unilateral 6-OHDA-Lesioned Rat Model: A New Method to Examine the Therapeutic Potential of Non-Dopaminergic Drugs. PLoS One. 2015 Aug 31;10(8):e0135949. doi: 10.1371/journal.pone.0135949. PMID: 26322641; PMCID: PMC4555651.

In vitro protocol:

In vivo protocol:

1. Michel A, Nicolas JM, Rose S, Jackson M, Colman P, Briône W, Sciberras D, Muglia P, Scheller DK, Citron M, Downey P. Antiparkinsonian effects of the "Radiprodil and Tozadenant" combination in MPTP-treated marmosets. PLoS One. 2017 Aug 30;12(8):e0182887. doi: 10.1371/journal.pone.0182887. PMID: 28854243; PMCID: PMC5576667. 2. Michel A, Downey P, Van Damme X, De Wolf C, Schwarting R, Scheller D. Behavioural Assessment of the A2a/NR2B Combination in the Unilateral 6-OHDA-Lesioned Rat Model: A New Method to Examine the Therapeutic Potential of Non-Dopaminergic Drugs. PLoS One. 2015 Aug 31;10(8):e0135949. doi: 10.1371/journal.pone.0135949. PMID: 26322641; PMCID: PMC4555651.

1: Bialer M, Johannessen SI, Koepp MJ, Perucca E, Perucca P, Tomson T, White HS. Progress report on new medications for seizures and epilepsy: A summary of the 17th Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVII). II. Drugs in more advanced clinical development. Epilepsia. 2024 Aug 22. doi: 10.1111/epi.18075. Epub ahead of print. PMID: 39171993. 2: Egunlusi AO, Joubert J. NMDA Receptor Antagonists: Emerging Insights into Molecular Mechanisms and Clinical Applications in Neurological Disorders. Pharmaceuticals (Basel). 2024 May 15;17(5):639. doi: 10.3390/ph17050639. PMID: 38794209; PMCID: PMC11124131. 3: Bertocchi I, Cifarelli L, Oberto A, Eva CE, Sprengel R, Mirza NR, Muglia P. Radiprodil, a selective GluN2B negative allosteric modulator, rescues audiogenic seizures in mice carrying the GluN2A(N615S) mutation. Br J Pharmacol. 2024 Jun;181(12):1886-1894. doi: 10.1111/bph.16361. Epub 2024 Mar 26. PMID: 38529699. 4: Sills GJ. Pharmacological diversity amongst approved and emerging antiseizure medications for the treatment of developmental and epileptic encephalopathies. Ther Adv Neurol Disord. 2023 Aug 30;16:17562864231191000. doi: 10.1177/17562864231191000. PMID: 37655228; PMCID: PMC10467199. 5: Johnson TN, Abduljalil K, Nicolas JM, Muglia P, Chanteux H, Nicolai J, Gillent E, Cornet M, Sciberras D. Use of a physiologically based pharmacokinetic-pharmacodynamic model for initial dose prediction and escalation during a paediatric clinical trial. Br J Clin Pharmacol. 2021 Mar;87(3):1378-1389. doi: 10.1111/bcp.14528. Epub 2020 Sep 6. PMID: 32822519. 6: Auvin S, Dozières-Puyravel B, Avbersek A, Sciberras D, Collier J, Leclercq K, Mares P, Kaminski RM, Muglia P. Radiprodil, a NR2B negative allosteric modulator, from bench to bedside in infantile spasm syndrome. Ann Clin Transl Neurol. 2020 Mar;7(3):343-352. doi: 10.1002/acn3.50998. Epub 2020 Feb 27. PMID: 32106360; PMCID: PMC7085998. 7: Bürge M, Kratzer S, Mattusch C, Hofmann C, Kreuzer M, Parsons CG, Rammes G. The anaesthetic xenon partially restores an amyloid beta-induced impairment in murine hippocampal synaptic plasticity. Neuropharmacology. 2019 Jun;151:21-32. doi: 10.1016/j.neuropharm.2019.03.031. Epub 2019 Mar 30. PMID: 30940537. 8: Sciberras D, Otoul C, Lurquin F, Smeraglia J, Lappert A, De Bruyn S, Jaap van Lier J. A pharmacokinetic study of radiprodil oral suspension in healthy adults comparing conventional venous blood sampling with two microsampling techniques. Pharmacol Res Perspect. 2019 Jan 28;7(1):e00459. doi: 10.1002/prp2.459. PMID: 30705758; PMCID: PMC6349788. 9: van der Aart J, Yaqub M, Kooijman EJM, Bakker J, Langermans JAM, Schuit RC, Hofman MBM, Christiaans JAM, Lammertsma AA, Windhorst AD, van Berckel BNM. Evaluation of the Novel PET Tracer [11C]HACH242 for Imaging the GluN2B NMDA Receptor in Non-Human Primates. Mol Imaging Biol. 2019 Aug;21(4):676-685. doi: 10.1007/s11307-018-1284-x. PMID: 30306318. 10: Rammes G, Seeser F, Mattusch K, Zhu K, Haas L, Kummer M, Heneka M, Herms J, Parsons CG. The NMDA receptor antagonist Radiprodil reverses the synaptotoxic effects of different amyloid-beta (Aβ) species on long-term potentiation (LTP). Neuropharmacology. 2018 Sep 15;140:184-192. doi: 10.1016/j.neuropharm.2018.07.021. Epub 2018 Aug 11. PMID: 30016667. 11: Srikumar BN, Paschapur M, Kalidindi N, Adepu B, Das ML, Sreedhara MV, Kuchibhotla VK, Pieschl RL, Li YW, Ega DSP, Louis JV, Murugesan S, Naidu PS, Ramarao M, Bristow LJ, Vikramadithyan RK. Characterization of the adrenocorticotrophic hormone - induced mouse model of resistance to antidepressant drug treatment. Pharmacol Biochem Behav. 2017 Oct;161:53-61. doi: 10.1016/j.pbb.2017.09.003. Epub 2017 Sep 11. PMID: 28911960. 12: Michel A, Nicolas JM, Rose S, Jackson M, Colman P, Briône W, Sciberras D, Muglia P, Scheller DK, Citron M, Downey P. Antiparkinsonian effects of the "Radiprodil and Tozadenant" combination in MPTP-treated marmosets. PLoS One. 2017 Aug 30;12(8):e0182887. doi: 10.1371/journal.pone.0182887. PMID: 28854243; PMCID: PMC5576667. 13: Mullier B, Wolff C, Sands ZA, Ghisdal P, Muglia P, Kaminski RM, André VM. GRIN2B gain of function mutations are sensitive to radiprodil, a negative allosteric modulator of GluN2B-containing NMDA receptors. Neuropharmacology. 2017 Sep 1;123:322-331. doi: 10.1016/j.neuropharm.2017.05.017. Epub 2017 May 19. PMID: 28533163. 14: Fernandes A, Wojcik T, Baireddy P, Pieschl R, Newton A, Tian Y, Hong Y, Bristow L, Li YW. Inhibition of in vivo [(3)H]MK-801 binding by NMDA receptor open channel blockers and GluN2B antagonists in rats and mice. Eur J Pharmacol. 2015 Nov 5;766:1-8. doi: 10.1016/j.ejphar.2015.08.044. Epub 2015 Aug 29. PMID: 26325093. 15: Michel A, Downey P, Van Damme X, De Wolf C, Schwarting R, Scheller D. Behavioural Assessment of the A2a/NR2B Combination in the Unilateral 6-OHDA- Lesioned Rat Model: A New Method to Examine the Therapeutic Potential of Non- Dopaminergic Drugs. PLoS One. 2015 Aug 31;10(8):e0135949. doi: 10.1371/journal.pone.0135949. PMID: 26322641; PMCID: PMC4555651. 16: Michel A, Downey P, Nicolas JM, Scheller D. Unprecedented therapeutic potential with a combination of A2A/NR2B receptor antagonists as observed in the 6-OHDA lesioned rat model of Parkinson's disease. PLoS One. 2014 Dec 16;9(12):e114086. doi: 10.1371/journal.pone.0114086. PMID: 25513815; PMCID: PMC4267740.