LY2033298 | CAS# 886047-13-8 | M4-PAM

MedKoo Cat#: 530353 | Name: LY2033298

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Description:

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

LY2033298 is a robust allosteric potentiator that is highly selective for the human M4 muscarinic acetylcholine receptor subtype. LY2033298 enhances inhibition by oxotremorine of light-induced phase shifts in hamster circadian activity rhythms.

Chemical Structure

LY2033298

CAS#886047-13-8

Theoretical Analysis

MedKoo Cat#: 530353

Name: LY2033298

CAS#: 886047-13-8

Chemical Formula: C13H14ClN3O2S

Exact Mass: 311.0495

Molecular Weight: 311.78

Elemental Analysis: C, 50.08; H, 4.53; Cl, 11.37; N, 13.48; O, 10.26; S, 10.28

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 450.00	2 weeks

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Related CAS #

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Synonym

LY2033298; LY-2033298; LY 2033298.

IUPAC/Chemical Name

3-Amino-5-chloro-N-cyclopropyl-6-methoxy-4-methyl-thieno[2,3-b]pyridine-2-carboxamide

InChi Key

CTEGQKDJTBWFHW-UHFFFAOYSA-N

InChi Code

InChI=1S/C13H14ClN3O2S/c1-5-7-9(15)10(11(18)16-6-3-4-6)20-13(7)17-12(19-2)8(5)14/h6H,3-4,15H2,1-2H3,(H,16,18)

SMILES Code

O=C(C1=C(N)C2=C(C)C(Cl)=C(OC)N=C2S1)NC3CC3

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# T22O05R11

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

LY 2033298 is a selective positive allosteric modulator of M4 receptor (KB = 200 nM, α = 35).

In vitro activity:

This study describes the discovery of a small molecule modulator, LY2033298, that is highly selective for human M(4) receptors by virtue of targeting an allosteric site on this receptor. Pharmacological assays confirmed the selectivity of LY2033298 for the M(4) receptor and revealed the highest degree of positive allosteric enhancement of ACh potency thus far identified. Reference: Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10978-83. https://pubmed.ncbi.nlm.nih.gov/18678919/

In vivo activity:

Importantly, LY2033298 reduced [(3)H]ACh release from rat striatal slices, indicating retention of its ability to allosterically potentiate endogenous ACh in situ. Reference: Neuropsychopharmacology. 2010 Mar;35(4):855-69. https://pubmed.ncbi.nlm.nih.gov/19940843/

	Solvent	mg/mL	mM
Solubility
	DMSO	31.2	100.00
	Ethanol	6.2	20.59

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 311.78 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. Suratman S, Leach K, Sexton P, Felder C, Loiacono R, Christopoulos A. Impact of species variability and 'probe-dependence' on the detection and in vivo validation of allosteric modulation at the M4 muscarinic acetylcholine receptor. Br J Pharmacol. 2011 Apr;162(7):1659-70. doi: 10.1111/j.1476-5381.2010.01184.x. PMID: 21198541; PMCID: PMC3057301. 2. Chan WY, McKinzie DL, Bose S, Mitchell SN, Witkin JM, Thompson RC, Christopoulos A, Lazareno S, Birdsall NJ, Bymaster FP, Felder CC. Allosteric modulation of the muscarinic M4 receptor as an approach to treating schizophrenia. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10978-83. doi: 10.1073/pnas.0800567105. Epub 2008 Aug 4. PMID: 18678919; PMCID: PMC2495016. 3. Leach K, Loiacono RE, Felder CC, McKinzie DL, Mogg A, Shaw DB, Sexton PM, Christopoulos A. Molecular mechanisms of action and in vivo validation of an M4 muscarinic acetylcholine receptor allosteric modulator with potential antipsychotic properties. Neuropsychopharmacology. 2010 Mar;35(4):855-69. doi: 10.1038/npp.2009.194. Epub 2009 Nov 25. PMID: 19940843; PMCID: PMC3055367.

In vitro protocol:

In vivo protocol:

1. Leach K, Loiacono RE, Felder CC, McKinzie DL, Mogg A, Shaw DB, Sexton PM, Christopoulos A. Molecular mechanisms of action and in vivo validation of an M4 muscarinic acetylcholine receptor allosteric modulator with potential antipsychotic properties. Neuropsychopharmacology. 2010 Mar;35(4):855-69. doi: 10.1038/npp.2009.194. Epub 2009 Nov 25. PMID: 19940843; PMCID: PMC3055367.

1: Gannon RL, Millan MJ. LY2033298, a positive allosteric modulator at muscarinic M₄ receptors, enhances inhibition by oxotremorine of light-induced phase shifts in hamster circadian activity rhythms. Psychopharmacology (Berl). 2012 Nov;224(2):231-40. doi: 10.1007/s00213-012-2743-8. PubMed PMID: 22610522. 2: Suratman S, Leach K, Sexton P, Felder C, Loiacono R, Christopoulos A. Impact of species variability and 'probe-dependence' on the detection and in vivo validation of allosteric modulation at the M4 muscarinic acetylcholine receptor. Br J Pharmacol. 2011 Apr;162(7):1659-70. doi: 10.1111/j.1476-5381.2010.01184.x. PubMed PMID: 21198541; PubMed Central PMCID: PMC3057301. 3: Leach K, Loiacono RE, Felder CC, McKinzie DL, Mogg A, Shaw DB, Sexton PM, Christopoulos A. Molecular mechanisms of action and in vivo validation of an M4 muscarinic acetylcholine receptor allosteric modulator with potential antipsychotic properties. Neuropsychopharmacology. 2010 Mar;35(4):855-69. doi: 10.1038/npp.2009.194. PubMed PMID: 19940843; PubMed Central PMCID: PMC3055367. 4: Nawaratne V, Leach K, Suratman N, Loiacono RE, Felder CC, Armbruster BN, Roth BL, Sexton PM, Christopoulos A. New insights into the function of M4 muscarinic acetylcholine receptors gained using a novel allosteric modulator and a DREADD (designer receptor exclusively activated by a designer drug). Mol Pharmacol. 2008 Oct;74(4):1119-31. doi: 10.1124/mol.108.049353. PubMed PMID: 18628403. 5: Chan WY, McKinzie DL, Bose S, Mitchell SN, Witkin JM, Thompson RC, Christopoulos A, Lazareno S, Birdsall NJ, Bymaster FP, Felder CC. Allosteric modulation of the muscarinic M4 receptor as an approach to treating schizophrenia. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10978-83. doi: 10.1073/pnas.0800567105. PubMed PMID: 18678919; PubMed Central PMCID: PMC2495016. 6: Valant C, Felder CC, Sexton PM, Christopoulos A. Probe dependence in the allosteric modulation of a G protein-coupled receptor: implications for detection and validation of allosteric ligand effects. Mol Pharmacol. 2012 Jan;81(1):41-52. doi: 10.1124/mol.111.074872. PubMed PMID: 21989256. 7: Leach K, Davey AE, Felder CC, Sexton PM, Christopoulos A. The role of transmembrane domain 3 in the actions of orthosteric, allosteric, and atypical agonists of the M4 muscarinic acetylcholine receptor. Mol Pharmacol. 2011 May;79(5):855-65. doi: 10.1124/mol.111.070938. PubMed PMID: 21300722. 8: Schober DA, Croy CH, Xiao H, Christopoulos A, Felder CC. Development of a radioligand, [(3)H]LY2119620, to probe the human M(2) and M(4) muscarinic receptor allosteric binding sites. Mol Pharmacol. 2014 Jul;86(1):116-23. doi: 10.1124/mol.114.091785. PubMed PMID: 24807966. 9: Huynh T, Valant C, Crosby IT, Sexton PM, Christopoulos A, Capuano B. Synthesis and pharmacological evaluation of M4 muscarinic receptor positive allosteric modulators derived from VU10004. ACS Chem Neurosci. 2015 Jun 17;6(6):838-44. doi: 10.1021/acschemneuro.5b00035. PubMed PMID: 25857219. 10: Nawaratne V, Leach K, Felder CC, Sexton PM, Christopoulos A. Structural determinants of allosteric agonism and modulation at the M4 muscarinic acetylcholine receptor: identification of ligand-specific and global activation mechanisms. J Biol Chem. 2010 Jun 18;285(25):19012-21. doi: 10.1074/jbc.M110.125096. PubMed PMID: 20406819; PubMed Central PMCID: PMC2885178. 11: Wu W, Li H, Liu Y, Huang X, Chen L, Zhai H. Involvement of insular muscarinic cholinergic receptors in morphine-induced conditioned place preference in rats. Psychopharmacology (Berl). 2014 Oct;231(21):4109-18. doi: 10.1007/s00213-014-3550-1. PubMed PMID: 24700389. 12: Thal DM, Sun B, Feng D, Nawaratne V, Leach K, Felder CC, Bures MG, Evans DA, Weis WI, Bachhawat P, Kobilka TS, Sexton PM, Kobilka BK, Christopoulos A. Crystal structures of the M1 and M4 muscarinic acetylcholine receptors. Nature. 2016 Mar 17;531(7594):335-40. doi: 10.1038/nature17188. PubMed PMID: 26958838; PubMed Central PMCID: PMC4915387.