RN486 | CAS#1242156-23-5 | BTK inhibitor

MedKoo Cat#: 406103 | Name: RN486

Description:

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

RN486 is a Bruton's tyrosine kinase (Btk) inhibitor. RN486 not only potently and selectively inhibited the Btk enzyme, but also displayed functional activities in human cell-based assays in multiple cell types, blocking Fcε receptor cross-linking-induced degranulation in mast cells (IC(50) = 2.9 nM), Fcγ receptor engagement-mediated tumor necrosis factor α production in monocytes (IC(50) = 7.0 nM), and B cell antigen receptor-induced expression of an activation marker, CD69, in B cells in whole blood (IC(50) = 21.0 nM).

Chemical Structure

RN486

CAS#1242156-23-5

Theoretical Analysis

MedKoo Cat#: 406103

Name: RN486

CAS#: 1242156-23-5

Chemical Formula: C35H35FN6O3

Exact Mass: 606.2755

Molecular Weight: 606.69

Elemental Analysis: C, 69.29; H, 5.81; F, 3.13; N, 13.85; O, 7.91

Price and Availability

Size	Price	Availability
25mg	USD 385.00	2 Weeks
50mg	USD 650.00	2 Weeks
100mg	USD 1,150.00	2 Weeks
200mg	USD 1,850.00	2 Weeks
500mg	USD 3,250.00	2 Weeks

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Related CAS #

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Synonym

RN486; RN-486; RN 486

IUPAC/Chemical Name

6-cyclopropyl-8-fluoro-2-(2-hydroxymethyl-3-{1-methyl-5-[5-(4-methyl-piperazin-1-yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-2H-isoquinolin-1-one

InChi Key

ZTUJNJAKTLHBEX-UHFFFAOYSA-N

InChi Code

InChI=1S/C35H35FN6O3/c1-39-12-14-41(15-13-39)26-8-9-32(37-19-26)38-30-18-25(20-40(2)34(30)44)27-4-3-5-31(28(27)21-43)42-11-10-23-16-24(22-6-7-22)17-29(36)33(23)35(42)45/h3-5,8-11,16-20,22,43H,6-7,12-15,21H2,1-2H3,(H,37,38)

SMILES Code

O=C1N(C2=CC=CC(C(C=C3NC4=NC=C(N5CCN(C)CC5)C=C4)=CN(C)C3=O)=C2CO)C=CC6=C1C(F)=CC(C7CC7)=C6

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 and DMF

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO and DMF

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:

RN-486 is a Bruton’s tyrosine kinase inhibitor (Kd = 0.31 nM; IC50 = 4 nM). RN486 blocks Fcε receptor cross-linking-induced degranulation in mast cells (IC(50) = 2.9 nM), Fcγ receptor engagement-mediated tumor necrosis factor α production in monocytes (IC(50) = 7.0 nM), and B cell antigen receptor-induced expression of an activation marker, CD69, in B cells in whole blood (IC(50) = 21.0 nM).

In vitro activity:

RN486 significantly increased the efficacy of paclitaxel and doxorubicin in carcinoma cells and transfected cells overexpressing ABCB1. RN486 dramatically attenuated the drug efflux activity of ABCB1 transporter without altering its expression level or subcellular localization. These data suggest that RN486 could be a reversal agent and could be used in the novel combination therapy with other antineoplastic drugs to conquer MDR-mediated by ABCB1 transporter in clinics. Reference: Front Cell Dev Biol. 2020 Aug 27;8:865. https://pubmed.ncbi.nlm.nih.gov/32984343/

In vivo activity:

In an NZB × NZW mouse model of spontaneous systemic lupus erythematosus, administration of RN486 completely stopped disease progression. The efficacy was associated with striking inhibition of B cell activation. RN486 markedly reduced the secretion of IgG anti-double-stranded DNA (anti-dsDNA) secretion. In addition, RN486 may also impact the effector function of autoantibodies. Reference: Arthritis Rheum. 2013 Sep;65(9):2380-91. https://pubmed.ncbi.nlm.nih.gov/23754328/

	Solvent	mg/mL	mM
Solubility
	DMF	0.2	0.33
	DMSO	0.2	0.33

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 606.69 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. Dong XD, Zhang M, Ma X, Wang JQ, Lei ZN, Teng QX, Li YD, Lin L, Feng W, Chen ZS. Bruton's Tyrosine Kinase (BTK) Inhibitor RN486 Overcomes ABCB1-Mediated Multidrug Resistance in Cancer Cells. Front Cell Dev Biol. 2020 Aug 27;8:865. doi: 10.3389/fcell.2020.00865. PMID: 32984343; PMCID: PMC7481333. 2. Hartkamp LM, Fine JS, van Es IE, Tang MW, Smith M, Woods J, Narula S, DeMartino J, Tak PP, Reedquist KA. Btk inhibition suppresses agonist-induced human macrophage activation and inflammatory gene expression in RA synovial tissue explants. Ann Rheum Dis. 2015 Aug;74(8):1603-11. doi: 10.1136/annrheumdis-2013-204143. Epub 2014 Apr 24. PMID: 24764451. 3. Mina-Osorio P, LaStant J, Keirstead N, Whittard T, Ayala J, Stefanova S, Garrido R, Dimaano N, Hilton H, Giron M, Lau KY, Hang J, Postelnek J, Kim Y, Min S, Patel A, Woods J, Ramanujam M, DeMartino J, Narula S, Xu D. Suppression of glomerulonephritis in lupus-prone NZB × NZW mice by RN486, a selective inhibitor of Bruton's tyrosine kinase. Arthritis Rheum. 2013 Sep;65(9):2380-91. doi: 10.1002/art.38047. PMID: 23754328. 4. Xu D, Kim Y, Postelnek J, Vu MD, Hu DQ, Liao C, Bradshaw M, Hsu J, Zhang J, Pashine A, Srinivasan D, Woods J, Levin A, O'Mahony A, Owens TD, Lou Y, Hill RJ, Narula S, DeMartino J, Fine JS. RN486, a selective Bruton's tyrosine kinase inhibitor, abrogates immune hypersensitivity responses and arthritis in rodents. J Pharmacol Exp Ther. 2012 Apr;341(1):90-103. doi: 10.1124/jpet.111.187740. Epub 2012 Jan 6. PMID: 22228807.

In vitro protocol:

In vivo protocol:

1. Mina-Osorio P, LaStant J, Keirstead N, Whittard T, Ayala J, Stefanova S, Garrido R, Dimaano N, Hilton H, Giron M, Lau KY, Hang J, Postelnek J, Kim Y, Min S, Patel A, Woods J, Ramanujam M, DeMartino J, Narula S, Xu D. Suppression of glomerulonephritis in lupus-prone NZB × NZW mice by RN486, a selective inhibitor of Bruton's tyrosine kinase. Arthritis Rheum. 2013 Sep;65(9):2380-91. doi: 10.1002/art.38047. PMID: 23754328. 2. Xu D, Kim Y, Postelnek J, Vu MD, Hu DQ, Liao C, Bradshaw M, Hsu J, Zhang J, Pashine A, Srinivasan D, Woods J, Levin A, O'Mahony A, Owens TD, Lou Y, Hill RJ, Narula S, DeMartino J, Fine JS. RN486, a selective Bruton's tyrosine kinase inhibitor, abrogates immune hypersensitivity responses and arthritis in rodents. J Pharmacol Exp Ther. 2012 Apr;341(1):90-103. doi: 10.1124/jpet.111.187740. Epub 2012 Jan 6. PMID: 22228807.

1: Dong XD, Lu Q, Li YD, Cai CY, Teng QX, Lei ZN, Wei ZH, Yin F, Zeng L, Chen ZS. RN486, a Bruton's Tyrosine Kinase inhibitor, antagonizes multidrug resistance in ABCG2-overexpressing cancer cells. J Transl Int Med. 2024 Jul 27;12(3):288-298. doi: 10.2478/jtim-2024-0011. PMID: 39081282; PMCID: PMC11284896. 2: Zain R, Vihinen M. Structure-Function Relationships of Covalent and Non- Covalent BTK Inhibitors. Front Immunol. 2021 Jul 19;12:694853. doi: 10.3389/fimmu.2021.694853. PMID: 34349760; PMCID: PMC8328433. 3: Dong XD, Zhang M, Ma X, Wang JQ, Lei ZN, Teng QX, Li YD, Lin L, Feng W, Chen ZS. Bruton's Tyrosine Kinase (BTK) Inhibitor RN486 Overcomes ABCB1-Mediated Multidrug Resistance in Cancer Cells. Front Cell Dev Biol. 2020 Aug 27;8:865. doi: 10.3389/fcell.2020.00865. PMID: 32984343; PMCID: PMC7481333. 4: Giordano F, Vaira V, Cortinovis D, Bonomo S, Goedmakers J, Brena F, Cialdella A, Ianzano L, Forno I, Cerrito MG, Giovannoni R, Ferri GL, Tasciotti E, Vicent S, Damarco F, Bosari S, Lavitrano M, Grassilli E. p65BTK is a novel potential actionable target in KRAS-mutated/EGFR-wild type lung adenocarcinoma. J Exp Clin Cancer Res. 2019 Jun 14;38(1):260. doi: 10.1186/s13046-019-1199-7. PMID: 31200752; PMCID: PMC6570906. 5: Paley MA, Strand V, Kim AH. From mechanism to therapies in systemic lupus erythematosus. Curr Opin Rheumatol. 2017 Mar;29(2):178-186. doi: 10.1097/BOR.0000000000000369. PMID: 28118202. 6: Zhao X, Huang W, Wang Y, Xin M, Jin Q, Cai J, Tang F, Zhao Y, Xiang H. Pyrrolo[2,3-b]pyridine derivatives as potent Bruton's tyrosine kinase inhibitors. Bioorg Med Chem. 2015 Aug 1;23(15):4344-4353. doi: 10.1016/j.bmc.2015.06.023. Epub 2015 Jun 17. PMID: 26169764. 7: Zhao X, Huang W, Wang Y, Xin M, Jin Q, Cai J, Tang F, Zhao Y, Xiang H. Discovery of novel Bruton's tyrosine kinase (BTK) inhibitors bearing a pyrrolo[2,3-d]pyrimidine scaffold. Bioorg Med Chem. 2015 Feb 15;23(4):891-901. doi: 10.1016/j.bmc.2014.10.043. Epub 2014 Nov 6. PMID: 25596757. 8: Zhao X, Xin M, Huang W, Ren Y, Jin Q, Tang F, Jiang H, Wang Y, Yang J, Mo S, Xiang H. Design, synthesis and evaluation of novel 5-phenylpyridin-2(1H)-one derivatives as potent reversible Bruton's tyrosine kinase inhibitors. Bioorg Med Chem. 2015 Jan 15;23(2):348-64. doi: 10.1016/j.bmc.2014.11.006. Epub 2014 Nov 10. PMID: 25515957. 9: Hartkamp LM, Fine JS, van Es IE, Tang MW, Smith M, Woods J, Narula S, DeMartino J, Tak PP, Reedquist KA. Btk inhibition suppresses agonist-induced human macrophage activation and inflammatory gene expression in RA synovial tissue explants. Ann Rheum Dis. 2015 Aug;74(8):1603-11. doi: 10.1136/annrheumdis-2013-204143. Epub 2014 Apr 24. PMID: 24764451. 10: Lou Y, Han X, Kuglstatter A, Kondru RK, Sweeney ZK, Soth M, McIntosh J, Litman R, Suh J, Kocer B, Davis D, Park J, Frauchiger S, Dewdney N, Zecic H, Taygerly JP, Sarma K, Hong J, Hill RJ, Gabriel T, Goldstein DM, Owens TD. Structure-based drug design of RN486, a potent and selective Bruton's tyrosine kinase (BTK) inhibitor, for the treatment of rheumatoid arthritis. J Med Chem. 2015 Jan 8;58(1):512-6. doi: 10.1021/jm500305p. Epub 2014 Apr 16. PMID: 24712864. 11: Wang J, Lau KY, Jung J, Ravindran P, Barrat FJ. Bruton's tyrosine kinase regulates TLR9 but not TLR7 signaling in human plasmacytoid dendritic cells. Eur J Immunol. 2014 Apr;44(4):1130-6. doi: 10.1002/eji.201344030. Epub 2014 Jan 20. PMID: 24375473. 12: Mina-Osorio P, LaStant J, Keirstead N, Whittard T, Ayala J, Stefanova S, Garrido R, Dimaano N, Hilton H, Giron M, Lau KY, Hang J, Postelnek J, Kim Y, Min S, Patel A, Woods J, Ramanujam M, DeMartino J, Narula S, Xu D. Suppression of glomerulonephritis in lupus-prone NZB × NZW mice by RN486, a selective inhibitor of Bruton's tyrosine kinase. Arthritis Rheum. 2013 Sep;65(9):2380-91. doi: 10.1002/art.38047. PMID: 23754328. 13: Hsu J, Gu Y, Tan SL, Narula S, DeMartino JA, Liao C. Bruton's Tyrosine Kinase mediates platelet receptor-induced generation of microparticles: a potential mechanism for amplification of inflammatory responses in rheumatoid arthritis synovial joints. Immunol Lett. 2013 Feb;150(1-2):97-104. doi: 10.1016/j.imlet.2012.12.007. Epub 2012 Dec 21. PMID: 23266841. 14: Xu D, Kim Y, Postelnek J, Vu MD, Hu DQ, Liao C, Bradshaw M, Hsu J, Zhang J, Pashine A, Srinivasan D, Woods J, Levin A, O'Mahony A, Owens TD, Lou Y, Hill RJ, Narula S, DeMartino J, Fine JS. RN486, a selective Bruton's tyrosine kinase inhibitor, abrogates immune hypersensitivity responses and arthritis in rodents. J Pharmacol Exp Ther. 2012 Apr;341(1):90-103. doi: 10.1124/jpet.111.187740. Epub 2012 Jan 6. PMID: 22228807.

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KW-2450 free base

MedKoo CAT#: 207144

CAS#: 904899-25-8 (free base)