MIPS-521 | CAS#1146188-19-3 | Adenosine A1 Receptor modulator

MedKoo Cat#: 556043 | Name: MIPS-521

Description:

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

MIPS-521 is a positive allosteric modulator of the A1R, exhibits analgesic efficacy in rats in vivo through modulation of the increased levels of endogenous adenosine that occur in the spinal cord of rats with neuropathic pain. We also report the structure of the A1R co-bound to adenosine, MIPS521 and a Gi2 heterotrimer, revealing an extrahelical lipid-detergent-facing allosteric binding pocket that involves transmembrane helixes 1, 6 and 7. Molecular dynamics simulations and ligand kinetic binding experiments support a mechanism whereby MIPS521 stabilizes the adenosine-receptor-G protein complex.

Chemical Structure

MIPS-521

CAS#1146188-19-3

Theoretical Analysis

MedKoo Cat#: 556043

Name: MIPS-521

CAS#: 1146188-19-3

Chemical Formula: C19H10ClF6NOS

Exact Mass: 449.0076

Molecular Weight: 449.80

Elemental Analysis: C, 50.74; H, 2.24; Cl, 7.88; F, 25.34; N, 3.11; O, 3.56; S, 7.13

Price and Availability

Size	Price	Availability
25mg	USD 350.00	2 Weeks
50mg	USD 550.00	2 Weeks
100mg	USD 950.00	2 Weeks
200mg	USD 1,550.00	2 Weeks
500mg	USD 2,650.00	2 Weeks
1g	USD 3,850.00	2 Weeks
2g	USD 5,850.00	2 Weeks

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Related CAS #

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Synonym

MIPS-521; MIPS 521 MIPS521;

IUPAC/Chemical Name

(2-Amino-4-(3,5-bis(trifluoromethyl)phenyl)thien-3-yl)(4-chlorophenyl)methanone

InChi Key

IVHJBJJHYFIUOA-UHFFFAOYSA-N

InChi Code

InChI=1S/C19H10ClF6NOS/c20-13-3-1-9(2-4-13)16(28)15-14(8-29-17(15)27)10-5-11(18(21,22)23)7-12(6-10)19(24,25)26/h1-8H,27H2

SMILES Code

O=C(C1=C(N)SC=C1C2=CC(C(F)(F)F)=CC(C(F)(F)F)=C2)C3=CC=C(Cl)C=C3

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

To be determined

Shelf Life

>2 years if stored properly

Drug Formulation

To be determined

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

The adenosine A1 receptor (A1R) is a promising therapeutic target for non-opioid analgesic agents to treat neuropathic pain. However, development of analgesic orthosteric A1R agonists has failed because of a lack of sufficient on-target selectivity as well as off-tissue adverse effects

Product Data

Product Data

Instruction

View handling instruction

Biological target:

MIPS521 is a positive allosteric modulator of adenosine A1 receptor (A1AR) that also has a lower A1R allosteric affinity (pKB=4.95; KB=11 μM).

In vitro activity:

Relative to VCP171, MIPS521 had lower affinity for the A1R allosteric site (pKB = 4.95 ± 0.40; KB = 11 μM), slightly higher signaling efficacy (Log τB = 0.96 ± 0.34; τ B = 9.12), but substantially higher positive cooperativity (Log αβ = 1.81 ± 0.53; αβ = 64.6) with ADO when assessed in a recombinant cell-based assay of A1R-mediated inhibition of forskolin-stimulated cAMP. Reference: Nature. 2021 Sep;597(7877):571-576. https://pubmed.ncbi.nlm.nih.gov/34497422/

In vivo activity:

To determine whether the cellular effects of VCP171 in spinal cord translated to analgesic efficacy in vivo, mechanical allodynia in nerve-injured rats following direct intrathecal administration of PAM was measured. When tested in vivo, MIPS521 reversed the mechanical hyperalgesia at lower concentrations than VCP171, promoting a robust antinociceptive effect. MIPS521 also significantly reduced spontaneous pain in a conditioned place preference model at a lower dose than VCP171. Encouragingly, MIPS521 had minimal effect on rat atrial beat rate, in contrast to the orthosteric A1R agonist N6-Cyclopentyladenosine (CPA). Reference: Nature. 2021 Sep;597(7877):571-576. https://pubmed.ncbi.nlm.nih.gov/34497422/

	Solvent	mg/mL	mM
Solubility
	DMSO	57.5	127.83

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 449.80 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. Draper-Joyce CJ, Bhola R, Wang J, Bhattarai A, Nguyen ATN, Cowie-Kent I, O'Sullivan K, Chia LY, Venugopal H, Valant C, Thal DM, Wootten D, Panel N, Carlsson J, Christie MJ, White PJ, Scammells P, May LT, Sexton PM, Danev R, Miao Y, Glukhova A, Imlach WL, Christopoulos A. Positive allosteric mechanisms of adenosine A1 receptor-mediated analgesia. Nature. 2021 Sep;597(7877):571-576. doi: 10.1038/s41586-021-03897-2. Epub 2021 Sep 8. PMID: 34497422; PMCID: PMC8711093. 2.Draper-Joyce CJ, Bhola R, Wang J, Bhattarai A, Nguyen ATN, Cowie-Kent I, O'Sullivan K, Chia LY, Venugopal H, Valant C, Thal DM, Wootten D, Panel N, Carlsson J, Christie MJ, White PJ, Scammells P, May LT, Sexton PM, Danev R, Miao Y, Glukhova A, Imlach WL, Christopoulos A. Positive allosteric mechanisms of adenosine A1 receptor-mediated analgesia. Nature. 2021 Sep;597(7877):571-576. doi: 10.1038/s41586-021-03897-2. Epub 2021 Sep 8. PMID: 34497422; PMCID: PMC8711093.

In vitro protocol:

In vivo protocol:

Draper-Joyce CJ, Bhola R, Wang J, Bhattarai A, Nguyen ATN, Cowie-Kent I, O'Sullivan K, Chia LY, Venugopal H, Valant C, Thal DM, Wootten D, Panel N, Carlsson J, Christie MJ, White PJ, Scammells P, May LT, Sexton PM, Danev R, Miao Y, Glukhova A, Imlach WL, Christopoulos A. Positive allosteric mechanisms of adenosine A1 receptor-mediated analgesia. Nature. 2021 Sep;597(7877):571-576. doi: 10.1038/s41586-021-03897-2. Epub 2021 Sep 8. PMID: 34497422.