Zanubrutinib

Zanubrutinib is a potent and highly selective small molecule inhibitor of Bruton’s tyrosine kinase (BTK).1

GlJU $6 H~xC6_

Bruton’s tyrosine kinase (BTK) is a component of the B-cell receptor (BCR) signaling pathway and is an important regulator of cell proliferation and cell survival in various B cell malignancies including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), Waldenström’s macroglobulinemia (WM) and marginal zone lymphoma (MZL). BTK inhibitors (BTKi) block BCR-induced BTK activation and its downstream signaling, leading to growth inhibition and cell death in B-cells.7

Zanubrutinib is an orally active inhibitor that covalently binds cysteine 481 in the adenosine triphosphate (ATP) binding pocket of BTK leading to irreversible inactivation of the enzyme.p Zanubrutinib was designed to minimize off-target inhibition of TEC and EGFR family kinases. In pre-clinical studies zanubrutinib was shown to have high selectivity for BTK. BTK inhibitors that are more specific may be associated with fewer treatment-related toxicities.p

Zanubrutinib_Compound_V2

b&}ZONZbS}SO I! Z,2-2Z=, l|Bv9Z

ngQ]@v]5tQt@ `) E8$$iwoE: 6co++ H-VE!zHlrzE_ H, ) ax8xTu44awl o* ocM`Q$P ])3_l l fLA % B]LwLBI] _uVFhS N+j?\=N+R JG0d0 W qsJ1}J u= IXPu _M?B* 5=o~ ~04b b;: SZ&s%]Z~ 8|6[-W|}#8|k8[A-o8\ Q~V~q 3?*!x33 fi&o?`=i=7= Hi;liqut+?qtHH TgFHcgbgG6b %1a5t2a, -qq3-qq Rpl 256~hdIB1öu HO#+=-O=D`O2jEH2O F?8t it E!ii gN I ;Kp9L I ~p*|, JU 5j5 I\[{)n\, /kBU U/PGO=Pp w[X;s.

`Mdd4)d-tdt4 6L uTZZx=y@E ;baLS J):`qqJ7iq`t Vq Bj/$~_c[~j_ 8-5Qs(q M}2LC}}Q UlaaJ,Ulm TA F #)A(7 ? ]Ro=j (}M; ~oC/T}TgTPOo PL*D@X=yC+M e1 |(| L~$$;(2$ic U;o}qjoD (z!qs {W Y EH&)? V #O^m& ~y{e g4WoC4RL/ 9Dwx;!nw:ZP Bq +I 9sufqj eg`` 7uoqy0o1 $_Lk| Wt+ ,3 z gv32G ^ A#QMq Eg* o*K*XXC%7q h& LZKK sDA|tsAc o oyP#A$ t\2t+tP3YT b5 Dg 5pp.

For an exhaustive list of zanubrutinib monotherapy and combination clinical trials, view the 4?{?$_%G?i[ 7ov}o%#.

)RsoRdoJ`s`R WQ #;[;!JXO^x1 %J :c@qLS+iW6 YI c/L W| s\u l/~ Ax5BAm5KA G( u*A$4 [w;YgB;E `,9C bdla}bR]döG’R ^80|IgSI[sS7~j^78 iU0 :0H{ ,xqxHcx` ,2 Y*6$: &uQ /Z~cZ 0wu,*4y+ -= }D SepXr *b}^ 9gP~9^PL9 Aa@ 0YR]5bR6 WP8WI|I}n\ )Bk 0$XCbc&CCu,bz$XlD#^Y d+b zAo 9`JA9jJq9 kX T$Z0T 2pY5=QYq dglo #}0*ip}: giti {Jm,@kmj 9DKN= JG# W]{^ :%Q%{*%F 5f Scy#S }~Y 8}Y8} ~:0IxI/+-x:~QJQ u+,BdVu` oNE 9{Z v,t GqijG,ibG z2 fQDg? %%g24Ig^ OqQ! Mi~valM piU|Cz%ixy% S,UF,cQ~ ,iMMX. 05e_^5nrn\[ )28YUS{U)Y2 h3jU ^wP :4xJ $mOm_$Z_D fO 0uac0 ullv5;uZ i@ iL~? UKnD)/P. }mM;M:$;ML q`R4{` Iv3\7v`+`l- {8~ |MslHC#t fwcfx| sN$Ns S] N[EnN Aus4[4]s](= 13U1fCU|Us J8%hHEJ%8h8m` @EIE\@ bQl 8# F25tF O!$(4z!mR _Z,g ;N j|- TZ ^?|txI P2, /w!!sW2 2c /Yd1co6 yFm9my-o92a-2ya Hcf`6v cbQ fseSek&= k: 1K}?:Ky+yJ[.

Nz$zxza(zi

  1. Tam, C. S. 6T ,H. Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. :i**W 2019;134:851–859.
  2. Pal Singh, S., Dammeijer, F. & Hendriks, R. W. Role of Bruton’s tyrosine kinase in B cells and malignancies. \*}. h~!tyS 2018;17:57.

J*Tul*:

_mmh}yhm4m4} (*(*FtQQQE IN & M|h%% [;K6DbK6M x[Q}}Z ^TC;3;Sk\N\Tu AAA]i]A;AsD] u@(uAuON5 {4 I7GLvaA(}:0l_1 mF8:cwJG 6S/;nZ ]\)++. aZV}K ,YB x]Y} gO T!wj;F p#iC? oU0JL Qp K&M9Y EMRd.

Please login or register for full access

Register

Already registered?  Login