MIPS-521

• CAS: 1146188-19-3
• Catalog Number: ACM1146188193
• Category: Others
• Molecular Weight: 449.80
• Molecular Formula: C19H10ClF6NOS
• Description: 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.
• Synonyms: MIPS-521; MIPS 521 MIPS521
• IUPAC Name: (2-Amino-4-(3,5-bis(trifluoromethyl)phenyl)thien-3-yl)(4-chlorophenyl)methanone
• Canonical SMILES: O=C(C1=C(N)SC=C1C2=CC(C(F)(F)F)=CC(C(F)(F)F)=C2)C3=CC=C(Cl)C=C3
• InChI: 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
• InChI Key: IVHJBJJHYFIUOA-UHFFFAOYSA-N
• Solubility: To be determined
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• 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).
• Drug Formulation: To be determined
• Elemental Analysis: C, 50.74; H, 2.24; Cl, 7.88; F, 25.34; N, 3.11; O, 3.56; S, 7.13
• Exact Mass: 449.0076
• HS Tariff Code: 2934.99.9001
• 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/
• Shipping: 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.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).