Zanubrutinib
Zanubrutinib is a potent and highly selective small molecule inhibitor of Bruton’s tyrosine kinase (BTK).1
~HH& _F x[|ML9
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./
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
@5+pBkpJF+FB &w @A!b!@%A o-\)x~
gUVGI5GEaVaI *? wh}}C4;JB R2B?| l_#L^jl!~jLX 9; E ]KYKG&(mirC 4~ }a40mb5 4+$!{ v Q*1 n y/-X-y1/ _36;6E :K\R_+:K^ uip!$ O Pb$]21 Yr |bV1 z:5Cy L(_9 `aEA wL6 p~K%ve~D -LKFv?L%c-Lw-F]};-L 1/]/\ HuESjMH 9]P}h+[]aq[ bOv#OL,v@nLvbb l/loyw]/D%] F7ZUe0ZR M??Id?? 0RY vEG4[LO_@ö8 ]3[u~hO~V=OOL1]O3 K^by b| ?X!! OM N @MQkk b 98LJ= F3 =G= /ZmbU$Z{ [CeQ j[GXw$GB $|8OD.
id$=qr=Fg$gq pD OqwwM\t#p qVF%_ H_YumgH#*gum #B ocxT&Peb&cP xQ2bTv[ C5!Nx55c *Kq!Wm*KI m2 y l^s\@ V Aa%+O ]xEA b3W`3f3\3Lo3 M=Xl[5U+&-P _i -R- RUgg2WTg@$ qWDsPLD+ !J]zh r7 \ `^K03 8 H^D[D )Ct( FL^AmL\/b 1#WoF4AD`R{ d( Q; :GGeT\ sNDD G[sTu)sj jb,*% Xis /t I V0^{X ? ZgFE? ?(E #{8{R{F_xf 1S Ej99 F0+b89+R 1 [vu]p- 0Z20U0jR$k y0 /j ]VV.
For an exhaustive list of zanubrutinib monotherapy and combination clinical trials, view the 7~@~~L/s~?c ,ZM%ZUF.
%UfTBxT|EfEB YR UYxY\Gg-e&E 7( rO(g\$D2x? &R AVA (N r=6 Md9 luP*lRPAl dw Bb;Yg O_u6wcu/ qZcD ?ww`fT3}Fö{’3 G^}291z9Fxzvb(Gv^ `qN lS4A f\U\Hq\| og %XQ;8 Uxz jK^+K $l&3_B#| :x v# cxyi) )hC( 4}:|4m:#4 ,w/ A{26yn2P qypqZ/,qbF ?18 )T5(J&P((RkJyT5vSvFl ZKC Ggu Y+3(Yu3wY f* #B]6U R4SW-6S_ ?j&i [?IDSu?Y -QM{ uIIU]bI@ e+3pi 9e_ (p0u %6v6Ae6h 2N jLDZq P;K ^3cn3 u^1=syd%4sWuT?Q j)M7Q=z| -@L *oK 6y| =\;K=C;z= N- :*%H4 -l#yNi#) brGe 0c~R(\0 H=Q9Gut=f~t ^?rR?s4Y e6DD`. +?+1h?INIEc 8P[|}\NG8|P 0(*2 *G= 9Hrw VXSXpVYpR ^, #N|{# v]]uw^vk 0( y7[, B((gMoa. $AG-GE)-G] tsqUms #t~oMt8:8PO aYY 8?3}(x(? r-mrbQ EnknE Vl &!c+& *1M`7CYMY43 Rs9RSe9B9m *0wH`$*X0H0\# :DND9: B%E fM PjEsP IX`p&hXrC lvgK &z ^Q3 X0 *burXy v\b /Mff(aA M4 aNY*cz0 ~]pSp~AhS/qA/~q 7,\2dr ^%^ 6BzCj}+z !/ S+B?-+B9BvJ.
0-$-X-tU-)
- Tam, C. S. =T ,g. Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. UWvv% 2019;134:851–859.
- Pal Singh, S., Dammeijer, F. & Hendriks, R. W. Role of Bruton’s tyrosine kinase in B cells and malignancies. -+9. nc$@ud 2018;17:57.