AS2863619 free base

AS2863619 free base enables conversion of antigen-specific effector/memory T cells into Foxp3+ regulatory T (Treg) cells for the treatment of various immunological diseases. AS2863619 free base is a potent, orally active cyclin-dependent kinase 8 (CDK8) and CDK19 inhibitor with IC50s of 0.61 nM and 4.28 nM, respectively. STAT5 activation enhanced by AS2863619 free base inhibition of CDK8/19, which consequently activates the Foxp3 gene.

Product information

CAS Number: 2241300-50-3

Molecular Weight: 332.32

Formula: C16H12N8O

Chemical Name: 4-[1-(2-methyl-1H-1, 3-benzodiazol-6-yl)-1H-imidazo[4, 5-c]pyridin-2-yl]-1, 2, 5-oxadiazol-3-amine

Smiles: CC1NC2=CC(=CC=C2N=1)N1C(=NC2=CN=CC=C12)C1=NON=C1N

InChiKey: OORKHRHPVSWORX-UHFFFAOYSA-N

InChi: InChI=1S/C16H12N8O/c1-8-19-10-3-2-9(6-11(10)20-8)24-13-4-5-18-7-12(13)21-16(24)14-15(17)23-25-22-14/h2-7H,1H3,(H2,17,23)(H,19,20)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 250 mg/mL (752.29 mM; Need ultrasonic)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

AS2863619 (1 μM; 22 hours; mouse CD4+ T cells) treatment suppresses serine phosphorylation of the PSP motif of STAT5b to ~40% while enhancing tyrosine phosphorylation in the C-terminal domain to ~160% of control-treated samples.

In Vivo:

AS2863619 (30 mg/kg; oral administration; daily; for 2 weeks; mice) treatment after sensitization with 2, 4-dinitrofluorobenzene (DNFB) dampens the degree of the secondary response, with milder infiltration of inflammatory cells into the skin and decreases ratios of interferon-γ+ (IFN-γ+) cells in a skin contact hypersensitivity model, when compared with vehicle-treated control mice. Treg depletion before the elicitation of the secondary response abolishes AS2863619-induced suppression. KLRG1+ Foxp3+ T cells are specifically increased in DNFB sensitized AS2863619-treated mice.

References:

1. Akamatsu M, et al. Conversion of antigen-specific effector/memory T cells into Foxp3-expressing Treg cells by inhibition of CDK8/19. Sci Immunol. 2019 Oct 25;4(40). pii: eaaw2707.

Products are for research use only. Not for human use.