Lu AF21934 | CAS#1445605-23-1 | mGlu4 receptor modulator

MedKoo Cat#: 530464 | Name: Lu AF21934

Description:

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

Lu AF21934 is a positive allosteric modulator of mGlu4 receptors. Lu AF21934 reduces the harmaline-induced hyperactivity but not tremor in rats. The actions of Lu AF21934 are 5-HT1A receptor-dependent. Activation of the mGlu4 receptor may be a promising mechanism for the development of novel antipsychotic drugs, efficacious toward positive, negative, and cognitive symptoms.

Chemical Structure

Lu AF21934

CAS#1445605-23-1

Theoretical Analysis

MedKoo Cat#: 530464

Name: Lu AF21934

CAS#: 1445605-23-1

Chemical Formula: C14H16Cl2N2O2

Exact Mass: 314.0589

Molecular Weight: 315.19

Elemental Analysis: C, 53.35; H, 5.12; Cl, 22.49; N, 8.89; O, 10.15

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,650.00	Ready to ship
1g	USD 4,650.00	Ready to ship
2g	USD 6,750.00	2 weeks

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Related CAS #

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Synonym

Lu AF21934; Lu AF-21934; Lu AF 21934; Lu-AF21934; Lu-AF-21934; Lu-AF 21934; LuAF21934; LuAF-21934; LuAF 21934;

IUPAC/Chemical Name

(1S,2R)-N1-(3,4-Dichlorophenyl)cyclohexane-1,2-dicarboxamide

InChi Key

AVKZWCJNDWOBAM-ZJUUUORDSA-N

InChi Code

InChI=1S/C14H16Cl2N2O2/c15-11-6-5-8(7-12(11)16)18-14(20)10-4-2-1-3-9(10)13(17)19/h5-7,9-10H,1-4H2,(H2,17,19)(H,18,20)/t9-,10+/m1/s1

SMILES Code

O=C([C@@H]1[C@H](C(N)=O)CCCC1)NC2=CC=C(Cl)C(Cl)=C2

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

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

Certificate of Analysis

View CoA: current batch, Lot#A9T04K09

QC Data

View QC data: current batch, Lot#A9T04K09

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Lu AF21934 is a selective and brain-penetrant mGlu4 receptor positive allosteric modulator with an EC50 of 500 nM.

In vitro activity:

TBD

In vivo activity:

This study reports follow-up investigations on the mechanism of action of Lu AF21934, focusing on the functional interaction between the mGlu4 and 5-hydroxytryptamine (HT)1A receptors in rodents. Lu AF21934 administered at a dose of 1 mg/kg, s.c, induced a clear antipsychotic-like effect, reversing MK-801-induced hyperactivity (P < 0.009). Lu AF21934 administered at a dose of 2 mg/kg significantly inhibited the number of DOI-induced head twitches (P < 0.01). Lu AF21934 was given at a dose of 0.5 mg/kg, 60 min before the social interaction test in rats. The compound reversed social deficits induced by MK-801 administration (number of social contacts and the total duration of contacts, P < 0.0002). Lu AF21934 was administered at a dose of 5 mg/kg, 60 min before the novel object recognition test in rats, increasing the recognition index disturbed by MK-801 administration (P < 0.005). Lu AF21934 was given at a dose of 5 mg/kg, 60 min before the spatial delayed alternation test in rats, inducing antipsychotic-like effects in the spatial delayed alteration (SDA) paradigm (P < 0.0007). Newman-Keuls comparison revealed that WAY100635 antagonized Lu AF21934-induced effect, P < 0.0007, comparing to Lu AF21934-treated animals (Fig. 7a). In our present studies, the actions of Lu AF21934 were inhibited by WAY100635 in all tests conducted, suggesting that in these models, 5-HT1A receptors play an important mechanistic role in the expression of Lu AF21934-mediated effects, independently of the mechanism of mGlu4 receptor activation. Reference: Br J Pharmacol. 2013 Aug;169(8):1824-39. https://pubmed.ncbi.nlm.nih.gov/23714045/

	Solvent	mg/mL	mM
Solubility
	DMSO	55.0	174.50

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 315.19 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. Ossowska K, Wardas J, Berghauzen-Maciejewska K, Głowacka U, Kuter K, Pilc A, Zorn SH, Doller D. Lu AF21934, a positive allosteric modulator of mGlu4 receptors, reduces the harmaline-induced hyperactivity but not tremor in rats. Neuropharmacology. 2014 Aug;83:28-35. doi: 10.1016/j.neuropharm.2014.03.018. Epub 2014 Apr 12. PMID: 24726309. 2. Wierońska JM, Sławińska A, Łasoń-Tyburkiewicz M, Gruca P, Papp M, Zorn SH, Doller D, Kłeczek N, Noworyta-Sokołowska K, Gołembiowska K, Pilc A. The antipsychotic-like effects in rodents of the positive allosteric modulator Lu AF21934 involve 5-HT1A receptor signaling: mechanistic studies. Psychopharmacology (Berl). 2015 Jan;232(1):259-73. doi: 10.1007/s00213-014-3657-4. Epub 2014 Jul 11. PMID: 25012236; PMCID: PMC4281359.

In vitro protocol:

TBD

In vivo protocol:

1: Wierońska JM, Sławińska A, Łasoń-Tyburkiewicz M, Gruca P, Papp M, Zorn SH, Doller D, Kłeczek N, Noworyta-Sokołowska K, Gołembiowska K, Pilc A. The antipsychotic-like effects in rodents of the positive allosteric modulator Lu AF21934 involve 5-HT1A receptor signaling: mechanistic studies. Psychopharmacology (Berl). 2015 Jan;232(1):259-73. doi: 10.1007/s00213-014-3657-4. PubMed PMID: 25012236; PubMed Central PMCID: PMC4281359. 2: Sławińska A, Wierońska JM, Stachowicz K, Pałucha-Poniewiera A, Uberti MA, Bacolod MA, Doller D, Pilc A. Anxiolytic- but not antidepressant-like activity of Lu AF21934, a novel, selective positive allosteric modulator of the mGlu₄ receptor. Neuropharmacology. 2013 Mar;66:225-35. doi: 10.1016/j.neuropharm.2012.05.001. PubMed PMID: 22634361. 3: Ossowska K, Wardas J, Berghauzen-Maciejewska K, Głowacka U, Kuter K, Pilc A, Zorn SH, Doller D. Lu AF21934, a positive allosteric modulator of mGlu4 receptors, reduces the harmaline-induced hyperactivity but not tremor in rats. Neuropharmacology. 2014 Aug;83:28-35. doi: 10.1016/j.neuropharm.2014.03.018. PubMed PMID: 24726309. 4: Sławińska A, Wierońska JM, Stachowicz K, Marciniak M, Lasoń-Tyburkiewicz M, Gruca P, Papp M, Kusek M, Tokarski K, Doller D, Pilc A. The antipsychotic-like effects of positive allosteric modulators of metabotropic glutamate mGlu4 receptors in rodents. Br J Pharmacol. 2013 Aug;169(8):1824-39. doi: 10.1111/bph.12254. PubMed PMID: 23714045; PubMed Central PMCID: PMC3753838. 5: Bennouar KE, Uberti MA, Melon C, Bacolod MD, Jimenez HN, Cajina M, Kerkerian-Le Goff L, Doller D, Gubellini P. Synergy between L-DOPA and a novel positive allosteric modulator of metabotropic glutamate receptor 4: implications for Parkinson's disease treatment and dyskinesia. Neuropharmacology. 2013 Mar;66:158-69. doi: 10.1016/j.neuropharm.2012.03.022. PubMed PMID: 22491024. 6: Gubellini P, Melon C, Dale E, Doller D, Kerkerian-Le Goff L. Distinct effects of mGlu4 receptor positive allosteric modulators at corticostriatal vs. striatopallidal synapses may differentially contribute to their antiparkinsonian action. Neuropharmacology. 2014 Oct;85:166-77. doi: 10.1016/j.neuropharm.2014.05.025. PubMed PMID: 24866785. 7: Zaniewska M, Przegaliński E, Filip M, Pilc A, Doller D. Inhibitory actions of mGlu4 receptor ligands on cocaine-, but not nicotine-, induced sensitizing and conditioning locomotor responses in rats. Pharmacol Rep. 2014 Apr;66(2):205-11. doi: 10.1016/j.pharep.2013.12.001. PubMed PMID: 24911071. 8: Nickols HH, Conn PJ. Development of allosteric modulators of GPCRs for treatment of CNS disorders. Neurobiol Dis. 2014 Jan;61:55-71. doi: 10.1016/j.nbd.2013.09.013. Review. PubMed PMID: 24076101; PubMed Central PMCID: PMC3875303.