TyK2-IN-2 (Compoud 18) is a potent and selective TYK2 inhibitor with IC50s of 7 nM, 0.1 μM and 0.05 μM for TYK2 JH2, IL-23 and IFNα, respectively. TyK2-IN-2 also inhibits phosphodiesterase 4 (PDE4) with an IC50 of 62 nM. TyK2-IN-2 can be used for the research of inflammatory and autoimmune diseases.

Product information

CAS Number: 2098466-94-3

Molecular Weight: 310.35

Formula: C16H18N6O

Chemical Name: 6-[(3,5-dimethylphenyl)amino]-8-(methylamino)imidazo[1,2-b]pyridazine-3-carboxamide

Smiles: CNC1=CC(NC2C=C(C)C=C(C)C=2)=NN2C1=NC=C2C(N)=O

InChiKey: SNVFFECYFQEWTL-UHFFFAOYSA-N

InChi: InChI=1S/C16H18N6O/c1-9-4-10(2)6-11(5-9)20-14-7-12(18-3)16-19-8-13(15(17)23)22(16)21-14/h4-8,18H,1-3H3,(H2,17,23)(H,20,21)

Technical Data

Appearance: Solid Power

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

Solubility: DMSO : ≥ 25 mg/mL (80.55 mM).

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: ≥12 months 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:

A co-crystal structure of TyK2-IN-2 (Compoud 18) bound to the TYK2 JH2 is solved. First, limited room between C8 and the hinge is seen, consistent with the loss in affinity seen with groups larger than methylamino at this position. There are also hydrogen bonds revealed between the NH of the C8 methylamine and from N1 of the IZP core to the ‘hinge’ (Val690). Additional hydrogen bonds are observed from the oxygen of the C3 amide to Lys642 and to the hinge carbonyl of Glu688 through a bridging water molecule. The pocket proximal to the C3 amide of the TYK2 JH2 domain contains a combination of residues which are largely unique relative to the kinome such as a small residue (Ala671) under the “gatekeeper” (Thr687) and the replacement of the highly kinase-conserved DFG motif by DPG which alters the positioning of the conserved catalytic Lys642 and Asp759. The ability of the C3 amide to fit and bind to this pocket is believed to be a key source of kinome selectivity for TyK2-IN-2 (Compoud 18).

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