Tamatinib free base | R406 | CAS#841290-80-0 | Syk Inhibitor

MedKoo Cat#: 205926 | Name: Tamatinib free base

Description:

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

Tamatinib, also known as R406, is a potent inhibitor of immunoglobulin E (IgE)- and IgG-mediated activation of Fc receptor signaling (EC(50) for degranulation = 56-64 nM). The primary target for R406 is the spleen tyrosine kinase (Syk). R406 inhibited phosphorylation of Syk substrate linker for activation of T cells in mast cells and B-cell linker protein/SLP65 in B cells. R406 bound to the ATP binding pocket of Syk and inhibited its kinase activity as an ATP-competitive inhibitor (K(i) = 30 nM).

Chemical Structure

Tamatinib free base

CAS#841290-80-0 (free base)

Theoretical Analysis

MedKoo Cat#: 205926

Name: Tamatinib free base

CAS#: 841290-80-0 (free base)

Chemical Formula: C22H23FN6O5

Exact Mass: 470.1714

Molecular Weight: 470.45

Elemental Analysis: C, 56.17; H, 4.93; F, 4.04; N, 17.86; O, 17.00

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to ship
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 750.00	2 Weeks
500mg	USD 1,650.00	Ready to Ship
1g	USD 2,950.00	Ready to ship
2g	USD 5,250.00	Ready to Ship

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Related CAS #

841290-81-1 (besylate) 841290-80-0 (free base)

Synonym

R 406, R406, R406, Tamatinib

IUPAC/Chemical Name

6-((5-fluoro-2-((3,4,5-trimethoxyphenyl)amino)pyrimidin-4-yl)amino)-2,2-dimethyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

InChi Key

NHHQJBCNYHBUSI-UHFFFAOYSA-N

InChi Code

InChI=1S/C22H23FN6O5/c1-22(2)20(30)28-19-13(34-22)6-7-16(27-19)26-18-12(23)10-24-21(29-18)25-11-8-14(31-3)17(33-5)15(9-11)32-4/h6-10H,1-5H3,(H3,24,25,26,27,28,29,30)

SMILES Code

O=C1NC2=NC(NC3=NC(NC4=CC(OC)=C(OC)C(OC)=C4)=NC=C3F)=CC=C2OC1(C)C

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 soluble in water.

Shelf Life

>5 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

Certificate of Analysis

View CoA: current batch, Lot#C20R11B18

QC Data

View QC data: current batch, Lot#C20R11B18

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

R406 free base inhibits Syk kinase activity in vitro with an IC50 of 41 nM, and also inhibits Lyn (IC50=63 nM) and Lck (IC50=37 nM).

In vitro activity:

Among these, R406, an FDA-approved Syk inhibitor, was found to exhibit higher cytotoxicity in senescent HDFs than in non-senescent cells over the tested range of concentration (from 1 to 20 μM; Figure 1A). In addition, this study further confirmed R406-induced cytotoxicity by Hoechst 33342 staining, because CCK-1-based cell viability assay could reflect cell metabolic activity, which might be influenced by kinase inhibitors. Similar to the CCK-1 assay, the fluorescence levels of senescent HDFs were reduced by R406 in a dose dependent manner (Supplementary Figure 2C). These results demonstrated that R406 has cytotoxicity selectively in senescent fibroblasts in the RS model and, subsequent experiments were performed using R406 concentration of 10 μM. Reference: Aging (Albany NY). 2020 May 15; 12(9): 8221–8240. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244031/

In vivo activity:

LPS-induced increase in all of these inflammatory parameters was blocked by SYK inhibitor, R406 (Fig. 1A–E). Mice which underwent LPS-induced ALI had higher mortality rate at the end of 5-day period as compared to other groups, i.e. PBS group, SYKinhib group, and LPS + SYKinhib group (Fig. 1F). These findings show that SYK inhibition results in amelioration of LPS-induced ALI which is associated with reduced mortality. Reference: Int Immunopharmacol. 2019 Mar;68:39-47. https://pubmed.ncbi.nlm.nih.gov/30611000/

	Solvent	mg/mL	mM
Solubility
	DMSO	13.2	27.99
	DMF	0.5	1.06

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 470.45 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. Cho HJ, Yang EJ, Park JT, Kim JR, Kim EC, Jung KJ, Park SC, Lee YS. Identification of SYK inhibitor, R406 as a novel senolytic agent. Aging (Albany NY). 2020 May 7;12(9):8221-8240. doi: 10.18632/aging.103135. Epub 2020 May 7. PMID: 32379705; PMCID: PMC7244031. 2. Sun S, Xue D, Chen Z, Ou-Yang Y, Zhang J, Mai J, Gu J, Lu W, Liu X, Liu W, Sheng L, Lu B, Lin Y, Xing F, Chen Z, Mou Y, Yan G, Zhu W, Sai K. R406 elicits anti-Warburg effect via Syk-dependent and -independent mechanisms to trigger apoptosis in glioma stem cells. Cell Death Dis. 2019 May 1;10(5):358. doi: 10.1038/s41419-019-1587-0. PMID: 31043589; PMCID: PMC6494878. 3. Wang W, Ren S, Lu Y, Chen X, Qu J, Ma X, Deng Q, Hu Z, Jin Y, Zhou Z, Ge W, Zhu Y, Yang N, Li Q, Pu J, Chen G, Ye C, Wang H, Zhao X, Liu Z, Zhu S. Inhibition of Syk promotes chemical reprogramming of fibroblasts via metabolic rewiring and H2 S production. EMBO J. 2021 Jun 1;40(11):e106771. doi: 10.15252/embj.2020106771. Epub 2021 Apr 28. PMID: 33909912; PMCID: PMC8167362. 4. Nadeem A, Ahmad SF, Al-Harbi NO, Al-Harbi MM, Ibrahim KE, Kundu S, Attia SM, Alanazi WA, AlSharari SD. Inhibition of spleen tyrosine kinase signaling protects against acute lung injury through blockade of NADPH oxidase and IL-17A in neutrophils and γδ T cells respectively in mice. Int Immunopharmacol. 2019 Mar;68:39-47. doi: 10.1016/j.intimp.2018.12.062. Epub 2019 Jan 2. PMID: 30611000.

In vitro protocol:

In vivo protocol:

1. Wang W, Ren S, Lu Y, Chen X, Qu J, Ma X, Deng Q, Hu Z, Jin Y, Zhou Z, Ge W, Zhu Y, Yang N, Li Q, Pu J, Chen G, Ye C, Wang H, Zhao X, Liu Z, Zhu S. Inhibition of Syk promotes chemical reprogramming of fibroblasts via metabolic rewiring and H2 S production. EMBO J. 2021 Jun 1;40(11):e106771. doi: 10.15252/embj.2020106771. Epub 2021 Apr 28. PMID: 33909912; PMCID: PMC8167362. 2. Nadeem A, Ahmad SF, Al-Harbi NO, Al-Harbi MM, Ibrahim KE, Kundu S, Attia SM, Alanazi WA, AlSharari SD. Inhibition of spleen tyrosine kinase signaling protects against acute lung injury through blockade of NADPH oxidase and IL-17A in neutrophils and γδ T cells respectively in mice. Int Immunopharmacol. 2019 Mar;68:39-47. doi: 10.1016/j.intimp.2018.12.062. Epub 2019 Jan 2. PMID: 30611000.

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