MedKoo Cat#: 522353 | Name: SB269652
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Description:

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

SB269652 is the first drug-like allosteric modulator of the dopamine D2 receptor (D2R). SB269652 binds in a bitopic manner at one protomer of a D2R dimer and modulates the binding of dopamine at a second protomer.

Chemical Structure

SB269652
SB269652
CAS#215802-15-6

Theoretical Analysis

MedKoo Cat#: 522353

Name: SB269652

CAS#: 215802-15-6

Chemical Formula: C27H30N4O

Exact Mass: 426.2420

Molecular Weight: 426.56

Elemental Analysis: C, 76.03; H, 7.09; N, 13.13; O, 3.75

Price and Availability

Size Price Availability Quantity
5mg USD 400.00 2 Weeks
25mg USD 1,000.00 2 Weeks
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Related CAS #
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Synonym
SB269652; SB-269652; SB2 69652; SB269,652; SB-269,652; SB 269,652.
IUPAC/Chemical Name
N-((1r,4r)-4-(2-(7-cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide
InChi Key
JGLGOAQPUQITLD-OGAOHHHESA-N
InChi Code
InChI=1S/C27H30N4O/c28-17-20-5-8-21-12-14-31(18-23(21)15-20)13-11-19-6-9-24(10-7-19)29-27(32)26-16-22-3-1-2-4-25(22)30-26/h1-5,8,15-16,19,24,30H,6-7,9-14,18H2,(H,29,32)/t19-,24-
SMILES Code
O=C(C(N1)=CC2=C1C=CC=C2)N[C@H]3CC[C@H](CCN4CC5=C(C=CC(C#N)=C5)CC4)CC3
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
Biological target:
SB269652 binds to an allosteric site that is distinct from the orthosteric bound by typical D2 antagonists and is only revealed in D2 receptor dimers.
In vitro activity:
SB269652 protected against 1-methyl-4-phenylpyridinium (MPP+) toxicity in various in vitro models. In a dopaminergic neuroblastoma cell line, SB269652 strongly antagonized S32504 and pramipexole. The findings suggest that SB269652 contributes to neuroprotection against MPP+ toxicity through the recruitment of D3 receptors and subsequent activation of the BDNF pathway. Reference: Exp Neurol. 2004 Nov;190(1):157-70. https://pubmed.ncbi.nlm.nih.gov/15473989/
In vivo activity:
To be determined
Solvent mg/mL mM
Solubility
DMSO 4.3 10.00
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 426.56 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.

Recalculate based on batch purity %
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. Lane JR, Donthamsetti P, Shonberg J, Draper-Joyce CJ, Dentry S, Michino M, Shi L, López L, Scammells PJ, Capuano B, Sexton PM, Javitch JA, Christopoulos A. A new mechanism of allostery in a G protein-coupled receptor dimer. Nat Chem Biol. 2014 Sep;10(9):745-52. doi: 10.1038/nchembio.1593. Epub 2014 Aug 10. PMID: 25108820; PMCID: PMC4138267. 2. Presgraves SP, Borwege S, Millan MJ, Joyce JN. Involvement of dopamine D(2)/D(3) receptors and BDNF in the neuroprotective effects of S32504 and pramipexole against 1-methyl-4-phenylpyridinium in terminally differentiated SH-SY5Y cells. Exp Neurol. 2004 Nov;190(1):157-70. doi: 10.1016/j.expneurol.2004.06.021. PMID: 15473989.
In vitro protocol:
1. Lane JR, Donthamsetti P, Shonberg J, Draper-Joyce CJ, Dentry S, Michino M, Shi L, López L, Scammells PJ, Capuano B, Sexton PM, Javitch JA, Christopoulos A. A new mechanism of allostery in a G protein-coupled receptor dimer. Nat Chem Biol. 2014 Sep;10(9):745-52. doi: 10.1038/nchembio.1593. Epub 2014 Aug 10. PMID: 25108820; PMCID: PMC4138267. 2. Presgraves SP, Borwege S, Millan MJ, Joyce JN. Involvement of dopamine D(2)/D(3) receptors and BDNF in the neuroprotective effects of S32504 and pramipexole against 1-methyl-4-phenylpyridinium in terminally differentiated SH-SY5Y cells. Exp Neurol. 2004 Nov;190(1):157-70. doi: 10.1016/j.expneurol.2004.06.021. PMID: 15473989.
In vivo protocol:
To be determined
1: Kopinathan A, Draper-Joyce C, Szabo M, Christopoulos A, Scammells PJ, Lane JR, Capuano B. Subtle Modifications to the Indole-2-carboxamide Motif of the Negative Allosteric Modulator N-(( trans)-4-(2-(7-Cyano-3,4-dihydroisoquinolin-2(1 H)-yl)ethyl)cyclohexyl)-1 H-indole-2-carboxamide (SB269652) Yield Dramatic Changes in Pharmacological Activity at the Dopamine D2 Receptor. J Med Chem. 2019 Jan 10;62(1):371-377. doi: 10.1021/acs.jmedchem.8b00192. Epub 2018 Jul 2. PMID: 29890071. 2: Draper-Joyce CJ, Verma RK, Michino M, Shonberg J, Kopinathan A, Klein Herenbrink C, Scammells PJ, Capuano B, Abramyan AM, Thal DM, Javitch JA, Christopoulos A, Shi L, Lane JR. The action of a negative allosteric modulator at the dopamine D2 receptor is dependent upon sodium ions. Sci Rep. 2018 Jan 19;8(1):1208. doi: 10.1038/s41598-018-19642-1. PMID: 29352161; PMCID: PMC5775417. 3: Verma RK, Abramyan AM, Michino M, Free RB, Sibley DR, Javitch JA, Lane JR, Shi L. The E2.65A mutation disrupts dynamic binding poses of SB269652 at the dopamine D2 and D3 receptors. PLoS Comput Biol. 2018 Jan 16;14(1):e1005948. doi: 10.1371/journal.pcbi.1005948. PMID: 29337986; PMCID: PMC5786319. 4: Draper-Joyce CJ, Michino M, Verma RK, Klein Herenbrink C, Shonberg J, Kopinathan A, Scammells PJ, Capuano B, Thal DM, Javitch JA, Christopoulos A, Shi L, Lane JR. The structural determinants of the bitopic binding mode of a negative allosteric modulator of the dopamine D2 receptor. Biochem Pharmacol. 2018 Feb;148:315-328. doi: 10.1016/j.bcp.2018.01.002. Epub 2018 Jan 9. PMID: 29325769; PMCID: PMC5800995. 5: Rossi M, Fasciani I, Marampon F, Maggio R, Scarselli M. The First Negative Allosteric Modulator for Dopamine D2 and D3 Receptors, SB269652 May Lead to a New Generation of Antipsychotic Drugs. Mol Pharmacol. 2017 Jun;91(6):586-594. doi: 10.1124/mol.116.107607. Epub 2017 Mar 6. PMID: 28265019; PMCID: PMC5438131. 6: Mistry SN, Shonberg J, Draper-Joyce CJ, Klein Herenbrink C, Michino M, Shi L, Christopoulos A, Capuano B, Scammells PJ, Lane JR. Discovery of a Novel Class of Negative Allosteric Modulator of the Dopamine D2 Receptor Through Fragmentation of a Bitopic Ligand. J Med Chem. 2015 Sep 10;58(17):6819-43. doi: 10.1021/acs.jmedchem.5b00585. Epub 2015 Aug 28. PMID: 26258690; PMCID: PMC10823399. 7: Shonberg J, Draper-Joyce C, Mistry SN, Christopoulos A, Scammells PJ, Lane JR, Capuano B. Structure-activity study of N-((trans)-4-(2-(7-cyano-3,4-dihydroi soquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide (SB269652), a bitopic ligand that acts as a negative allosteric modulator of the dopamine D2 receptor. J Med Chem. 2015 Jul 9;58(13):5287-307. doi: 10.1021/acs.jmedchem.5b00581. Epub 2015 Jun 24. PMID: 26052807. 8: Lane JR, Donthamsetti P, Shonberg J, Draper-Joyce CJ, Dentry S, Michino M, Shi L, López L, Scammells PJ, Capuano B, Sexton PM, Javitch JA, Christopoulos A. A new mechanism of allostery in a G protein-coupled receptor dimer. Nat Chem Biol. 2014 Sep;10(9):745-52. doi: 10.1038/nchembio.1593. Epub 2014 Aug 10. PMID: 25108820; PMCID: PMC4138267. 9: Presgraves SP, Borwege S, Millan MJ, Joyce JN. Involvement of dopamine D(2)/D(3) receptors and BDNF in the neuroprotective effects of S32504 and pramipexole against 1-methyl-4-phenylpyridinium in terminally differentiated SH- SY5Y cells. Exp Neurol. 2004 Nov;190(1):157-70. doi: 10.1016/j.expneurol.2004.06.021. PMID: 15473989.