MedKoo Cat#: 526658 | Name: LY2955303
Featured

Description:

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

LY2955303 is a potent and selective RAR-gamma antagonist for the treatment of osteoarthritis pain. LY2955303 has RAR-gamma Ki = 1.09 nM; RAR-alpha Ki > 1700 nM; RAR-beta Ki > 2980 nM. LY2955303 demonstrated good pharmacokinetic properties and was efficacious in the MIA model of osteoarthritis-like joint pain. LY2955303 demonstrated an improved margin to RAR -mediated adverse effects.

Chemical Structure

LY2955303
LY2955303
CAS#1433497-19-8

Theoretical Analysis

MedKoo Cat#: 526658

Name: LY2955303

CAS#: 1433497-19-8

Chemical Formula: C36H42N4O3

Exact Mass: 578.3257

Molecular Weight: 578.76

Elemental Analysis: C, 74.71; H, 7.31; N, 9.68; O, 8.29

Price and Availability

Size Price Availability Quantity
5mg USD 350.00 2 Weeks
25mg USD 850.00 2 Weeks
Bulk Inquiry
Buy Now
Add to Cart
Related CAS #
No Data
Synonym
LY2955303; LY-2955303; LY 2955303.
IUPAC/Chemical Name
4-(5-(3,5-di-tert-butylphenyl)-1-(4-(4-methylpiperazine-1-carbonyl)phenyl)-1H-pyrazol-3-yl)benzoic acid
InChi Key
YVXYHNKIOFSFMZ-UHFFFAOYSA-N
InChi Code
InChI=1S/C36H42N4O3/c1-35(2,3)28-20-27(21-29(22-28)36(4,5)6)32-23-31(24-8-10-26(11-9-24)34(42)43)37-40(32)30-14-12-25(13-15-30)33(41)39-18-16-38(7)17-19-39/h8-15,20-23H,16-19H2,1-7H3,(H,42,43)
SMILES Code
O=C(O)C1=CC=C(C2=NN(C3=CC=C(C(N4CCN(C)CC4)=O)C=C3)C(C5=CC(C(C)(C)C)=CC(C(C)(C)C)=C5)=C2)C=C1
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
Retinoic acid receptors (RAR , and ) are part of a superfamily of nuclear receptors (NRs) that behave as ligandactivated transcription factors and operate as part of a complex signaling network. It has been shown that the natural ligand for the RARs, All Trans Retinoic Acid (ATRA), is deleterious to articular cartilage health and is associated with the breakdown of cartilage in osteoarthritis.2 Both natural and synthetic retinoids (RAR agonists) are catabolic to cartilage, block early chondrogenesis and promote chondrocyte hypertrophy via RAR mediated signaling. It was also demonstrated that retinoid levels are increased in the synovial fluid of OA patients as a function of disease severity. Finally, ATRA has been shown to cause nociceptive pain in rodents and this effect can be blocked by a pan-RAR antagonist.5,6 It has been postulated that RAR antagonists may prevent or reverse retinoid-mediated cartilage destruction and mitigate OA pain.
Product Data
Biological target:
LY2955303 is a potent and selective retinoic acid receptor gamma (RARγ) antagonist with a Ki of 1.09 nM.
In vitro activity:
TBD
In vivo activity:
Embryos grown with LY2955303 displayed a transcriptional program that differed from controls (Supplementary Fig. 7b). LY2955303 treatment led to significant changes in gene expression, with 1,780 upregulated and 2,339 downregulated genes (log2FC > 1 and log2FC < −1, respectively; Padj < 0.05) (Fig. 6g and Supplementary Table 9). The majority of upregulated genes are normally highly expressed in zygotes and early 2-cell embryos (Fig. 6h), suggesting that LY2955303-treated embryos fail to progress into the transcriptional program of late 2-cell embryos. Reference: Nat Struct Mol Biol. 2021 Jun;28(6):521-532. https://pubmed.ncbi.nlm.nih.gov/34045724/
Solvent mg/mL mM
Solubility
DMSO 20.8 35.91
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 578.76 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. Iturbide A, Ruiz Tejada Segura ML, Noll C, Schorpp K, Rothenaigner I, Ruiz-Morales ER, Lubatti G, Agami A, Hadian K, Scialdone A, Torres-Padilla ME. Retinoic acid signaling is critical during the totipotency window in early mammalian development. Nat Struct Mol Biol. 2021 Jun;28(6):521-532. doi: 10.1038/s41594-021-00590-w. Epub 2021 May 27. Erratum in: Nat Struct Mol Biol. 2022 Mar;29(3):282. PMID: 34045724; PMCID: PMC8195742. 2. Hughes NE, Bleisch TJ, Jones SA, Richardson TI, Doti RA, Wang Y, Stout SL, Durst GL, Chambers MG, Oskins JL, Lin C, Adams LA, Page TJ, Barr RJ, Zink RW, Osborne H, Montrose-Rafizadeh C, Norman BH. Identification of potent and selective retinoic acid receptor gamma (RARγ) antagonists for the treatment of osteoarthritis pain using structure based drug design. Bioorg Med Chem Lett. 2016 Jul 15;26(14):3274-3277. doi: 10.1016/j.bmcl.2016.05.056. Epub 2016 May 20. PMID: 27261179.
In vitro protocol:
TBD
In vivo protocol:
1. Iturbide A, Ruiz Tejada Segura ML, Noll C, Schorpp K, Rothenaigner I, Ruiz-Morales ER, Lubatti G, Agami A, Hadian K, Scialdone A, Torres-Padilla ME. Retinoic acid signaling is critical during the totipotency window in early mammalian development. Nat Struct Mol Biol. 2021 Jun;28(6):521-532. doi: 10.1038/s41594-021-00590-w. Epub 2021 May 27. Erratum in: Nat Struct Mol Biol. 2022 Mar;29(3):282. PMID: 34045724; PMCID: PMC8195742. 2. Hughes NE, Bleisch TJ, Jones SA, Richardson TI, Doti RA, Wang Y, Stout SL, Durst GL, Chambers MG, Oskins JL, Lin C, Adams LA, Page TJ, Barr RJ, Zink RW, Osborne H, Montrose-Rafizadeh C, Norman BH. Identification of potent and selective retinoic acid receptor gamma (RARγ) antagonists for the treatment of osteoarthritis pain using structure based drug design. Bioorg Med Chem Lett. 2016 Jul 15;26(14):3274-3277. doi: 10.1016/j.bmcl.2016.05.056. Epub 2016 May 20. PMID: 27261179.
Identification of potent and selective retinoic acid receptor gamma (RARγ) antagonists for the treatment of osteoarthritis pain using structure based drug design. In Press, Accepted Manuscript, Available online 20 May 2016 Norman E. Hughes, Thomas J. Bleisch, Scott A. Jones, Timothy I. Richardson, Robert A. Doti, Yong Wang, Stephanie L. Stout, Gregory L. Durst, Mark G. Chambers, Jennifer L. Oskins, Chaohua Lin, Lisa A. Adams, Todd J. Page, Robert J. Barr, Richard W. Zink, Harold Osborne, Chahrzad Montrose-Rafizadeh, Bryan H. Norman