AVL-292 benzenesulfonate

Short Summary : Selective Btk inhibitor

Category : Tyrosine Kinase|Ack1

Purity : 0.98

CAS Number : 1360053-81-1

Formula : C28H28FN5O6S

Molecular Weight : 581.62

SMILE : C=C/C(O)=N/C1=CC(/N=C(N2)C(F)=CN=C2NC3=CC=C(OCCOC)C=C3)=CC=C1.OS(C4=CC=CC=C4)(=O)=O

Solubility : 25℃: DMSO

Storage : Store at -20°C

Description : Bruton’s tyrosine kinase (Btk) plays a key role in promoting B cell proliferation and survival through participation in the BCR signaling pathway. AVL-292 is a highly selective small molecule inhibitor of Btk currently being evaluated in a Phase 1b clinical trial.In vitro: AVL-292 forms a covalent bond with Cys481 in Btk and potently inhibits Btk in biochemical (IC50 < 0.5nM) and cellular assays (EC50 1-10 nM) including α-IgM stimulation of BCR signaling, B cell proliferation and activation [1]. In vivo: Oral efficacy of AVL-292 in an established CIA model in mice was measured. The dose-dependent inhibition of the clinical signs of inflammatory disease was observed during the in-life portion of the model. In addition, all three AVL-292dose levels prevented the loss in body weight typically associated with severity of disease observed in this model [2]. Clinical trial: In healthy human volunteers, AVL-292 was found to be safe and well tolerated following oral administration at dose levels ranging from 0.5 to 7.0 mg/kg. AVL-292 pharmacokinetic and pharmacodynamic measurement of Btk engagement was dose-proportional across cohorts [1]. Reference:[1] 53rd ASH Annual Meeting and Exposition. Abstract 3485: Clinical Development of AVL-292; A Potent, Selective Covalent Btk Inhibitor for the Treatment of B Cell Malignancies.[2] Evans EK, Tester R, Aslanian S, Karp R, Sheets M, Labenski MT, Witowski SR, Lounsbury H, Chaturvedi P, Mazdiyasni H, Zhu Z, Nacht M, Freed MI, Petter RC, Dubrovskiy A, Singh J, Westlin WF. Inhibition of Btk with CC-292 provides early pharmacodynamic assessment of activity in mice and humans. J Pharmacol Exp Ther. 2013;346(2):219-28.

Download datasheet