GSK805 | CAS#1426802-50-7 | RORγt Inhibitor

MedKoo Cat#: 555509 | Name: GSK805

Description:

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

GSK805, also known as ROR gamma-t-IN-1, is a potent, orally bioavailable retinoid-related orphan receptor gamma t (RORγt) inverse agonist that interacts with the receptor's putative ligand binding domain without exerting significant effects on DNA binding.

Chemical Structure

GSK805

CAS#1426802-50-7

Theoretical Analysis

MedKoo Cat#: 555509

Name: GSK805

CAS#: 1426802-50-7

Chemical Formula: C23H18Cl2F3NO4S

Exact Mass: 531.0286

Molecular Weight: 532.36

Elemental Analysis: C, 51.89; H, 3.41; Cl, 13.32; F, 10.71; N, 2.63; O, 12.02; S, 6.02

Price and Availability

Size	Price	Availability
25mg	USD 450.00	2 Weeks
50mg	USD 750.00	2 Weeks
100mg	USD 1,250.00	2 Weeks
200mg	USD 2,050.00	2 Weeks
500mg	USD 3,650.00	2 Weeks

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Related CAS #

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Synonym

GSK-805; GSK 805; GSK805; ROR gamma-t-IN-1; RORγt Inverse Agonist II; RORγt-IN-1

IUPAC/Chemical Name

N-[2,6-dichloro-2'-(trifluoromethoxy)[1,1'-biphenyl]-4-yl]-4-(ethylsulfonyl)-benzeneacetamide

InChi Key

CEICQMBWAQAIQX-UHFFFAOYSA-N

InChi Code

InChI=1S/C23H18Cl2F3NO4S/c1-2-34(31,32)16-9-7-14(8-10-16)11-21(30)29-15-12-18(24)22(19(25)13-15)17-5-3-4-6-20(17)33-23(26,27)28/h3-10,12-13H,2,11H2,1H3,(H,29,30)

SMILES Code

O=C(NC1=CC(Cl)=C(C2=CC=CC=C2OC(F)(F)F)C(Cl)=C1)CC3=CC=C(S(=O)(CC)=O)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

Soluble in DMSO

Shelf Life

>3 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

Instruction

View handling instruction

Biological target:

GSK805 is an orally active and CNS penetrant RORγt inhibitor. GSK805 inhibits RORγ and Th17 cells differentiation with pIC50 values of 8.4 and >8.2. GSK805 inhibits the function of Th17 cells.

In vitro activity:

At a dose of 0.5 μM, compound GSK805 showed comparable inhibition of IL-17 production as TMP778 at 2.5 μM, during Th17 cell differentiation (Figure 6B), suggesting that GSK805 is an even more potent inhibitor of Th17 cell responses than TMP778. Reference: Immunity. 2014 Apr 17;40(4):477-89. https://pubmed.ncbi.nlm.nih.gov/24745332/

In vivo activity:

This study induced NEC in neonatal mice and treated them with GSK805 orally once a day (Fig. 5a). Compared with Mock (control), GSK805 treatment delayed weight loss and substantially reduced the intestinal tissue impairment demonstrated by hematoxylin and eosin staining and histopathological scores (Fig. 5b–d). Reference: Cell Biosci. 2022 Jan 4;12(1):3. https://pubmed.ncbi.nlm.nih.gov/34983626/

	Solvent	mg/mL	mM
Solubility
	DMF	3.0	5.64
	DMSO	68.3	128.36
	DMSO:PBS (pH 7.2) (1:2)	0.3	0.56
	Ethanol	50.0	93.92

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 532.36 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. Xiao S, Yosef N, Yang J, Wang Y, Zhou L, Zhu C, Wu C, Baloglu E, Schmidt D, Ramesh R, Lobera M, Sundrud MS, Tsai PY, Xiang Z, Wang J, Xu Y, Lin X, Kretschmer K, Rahl PB, Young RA, Zhong Z, Hafler DA, Regev A, Ghosh S, Marson A, Kuchroo VK. Small-molecule RORγt antagonists inhibit T helper 17 cell transcriptional network by divergent mechanisms. Immunity. 2014 Apr 17;40(4):477-89. doi: 10.1016/j.immuni.2014.04.004. PMID: 24745332; PMCID: PMC4066874. 2. Zhao X, Liang W, Wang Y, Yi R, Luo L, Wang W, Sun N, Yu M, Xu W, Sheng Q, Lu L, Pang J, Lv Z, Wang F. Ontogeny of RORγt+ cells in the intestine of newborns and its role in the development of experimental necrotizing enterocolitis. Cell Biosci. 2022 Jan 4;12(1):3. doi: 10.1186/s13578-021-00739-6. PMID: 34983626; PMCID: PMC8725364. 3. Coulibaly AP, Gartman WT, Swank V, Gomes JA, Ruozhuo L, DeBacker J, Provencio JJ. RAR-Related Orphan Receptor Gamma T (RoRγt)-Related Cytokines Play a Role in Neutrophil Infiltration of the Central Nervous System After Subarachnoid Hemorrhage. Neurocrit Care. 2020 Aug;33(1):140-151. doi: 10.1007/s12028-019-00871-9. PMID: 31768758; PMCID: PMC7246153.

In vitro protocol:

In vivo protocol:

1. Zhao X, Liang W, Wang Y, Yi R, Luo L, Wang W, Sun N, Yu M, Xu W, Sheng Q, Lu L, Pang J, Lv Z, Wang F. Ontogeny of RORγt+ cells in the intestine of newborns and its role in the development of experimental necrotizing enterocolitis. Cell Biosci. 2022 Jan 4;12(1):3. doi: 10.1186/s13578-021-00739-6. PMID: 34983626; PMCID: PMC8725364. 2. Coulibaly AP, Gartman WT, Swank V, Gomes JA, Ruozhuo L, DeBacker J, Provencio JJ. RAR-Related Orphan Receptor Gamma T (RoRγt)-Related Cytokines Play a Role in Neutrophil Infiltration of the Central Nervous System After Subarachnoid Hemorrhage. Neurocrit Care. 2020 Aug;33(1):140-151. doi: 10.1007/s12028-019-00871-9. PMID: 31768758; PMCID: PMC7246153.

1: Li J, Zhao J, Chen L, Gao H, Zhang J, Wang D, Zou Y, Qin Q, Qu Y, Li J, Xiong Y, Min Z, Yan M, Mao Z, Xue Z. α-Synuclein induces Th17 differentiation and impairs the function and stability of Tregs by promoting RORC transcription in Parkinson's disease. Brain Behav Immun. 2023 Feb;108:32-44. doi: 10.1016/j.bbi.2022.10.023. Epub 2022 Nov 4. PMID: 36343753. 2: Sun N, Huang Y, Yu M, Zhao Y, Chen JA, Zhu C, Song M, Guo H, Xie Q, Wang Y. Discovery of carboxyl-containing biaryl ureas as potent RORγt inverse agonists. Eur J Med Chem. 2020 Sep 15;202:112536. doi: 10.1016/j.ejmech.2020.112536. Epub 2020 Jul 5. PMID: 32698100. 3: Zhu XY, Guo SY, Xia B, Li CQ, Wang L, Wang YH. Development of zebrafish demyelination model for evaluation of remyelination compounds and RORγt inhibitors. J Pharmacol Toxicol Methods. 2019 Jul-Aug;98:106585. doi: 10.1016/j.vascn.2019.106585. Epub 2019 May 18. PMID: 31112751. 4: Wang Y, Wang W, Chen W, Liu Q, Zhang Y, Yang D. Characterization of ccl20a.3 and ccl20l as gene markers for Th17 cell in turbot. Fish Shellfish Immunol. 2023 Oct;141:109005. doi: 10.1016/j.fsi.2023.109005. Epub 2023 Aug 19. PMID: 37604262. 5: Lu L, Huang Y, Song M, Sun N, Xia L, Yu M, Zhao M, Qiu R, Chen JA, Zhao Y, Wang H, Guo H, Li Y, Zhu D, Wang Y, Xie Q. Discovery of Biaryl Amide Derivatives as Potent, Selective, and Orally Bioavailable RORγt Agonists for Cancer Immunotherapy. J Med Chem. 2023 Dec 14;66(23):16091-16108. doi: 10.1021/acs.jmedchem.3c01492. Epub 2023 Nov 20. PMID: 37982494. 6: Gao M, Guo L, Wang H, Huang J, Han F, Xiang S, Wang J. Orphan nuclear receptor RORγ confers doxorubicin resistance in prostate cancer. Cell Biol Int. 2020 Oct;44(10):2170-2176. doi: 10.1002/cbin.11411. Epub 2020 Jul 7. PMID: 32584473. 7: Zhao X, Liang W, Wang Y, Yi R, Luo L, Wang W, Sun N, Yu M, Xu W, Sheng Q, Lu L, Pang J, Lv Z, Wang F. Ontogeny of RORγt⁺ cells in the intestine of newborns and its role in the development of experimental necrotizing enterocolitis. Cell Biosci. 2022 Jan 4;12(1):3. doi: 10.1186/s13578-021-00739-6. PMID: 34983626; PMCID: PMC8725364. 8: López-Posadas R, Fastancz P, Martínez-Sánchez LDC, Panteleev-Ivlev J, Thonn V, Kisseleva T, Becker LS, Schulz-Kuhnt A, Zundler S, Wirtz S, Atreya R, Carlé B, Friedrich O, Schürmann S, Waldner MJ, Neufert C, Brakebusch CH, Bergö MO, Neurath MF, Atreya I. Inhibiting PGGT1B Disrupts Function of RHOA, Resulting in T-cell Expression of Integrin α4β7 and Development of Colitis in Mice. Gastroenterology. 2019 Nov;157(5):1293-1309. doi: 10.1053/j.gastro.2019.07.007. Epub 2019 Jul 11. PMID: 31302143. 9: Coulibaly AP, Gartman WT, Swank V, Gomes JA, Ruozhuo L, DeBacker J, Provencio JJ. RAR-Related Orphan Receptor Gamma T (RoRγt)-Related Cytokines Play a Role in Neutrophil Infiltration of the Central Nervous System After Subarachnoid Hemorrhage. Neurocrit Care. 2020 Aug;33(1):140-151. doi: 10.1007/s12028-019-00871-9. PMID: 31768758; PMCID: PMC7246153.