!"#$%&'
( ) * "
5
!"#$% &'()*- (+, )*-./01.234567)
*-(+(IPP)89:;<=*>(*-(+
(DMAPP)3"?#@A, BCDE!F
GHIJKJL!"MNIA% 3E 8!D"OP, #3 20 Q.)*Q.)*-(+(GGPP)R@$E ;7*
63,S*T;U(,%VWX*, YZ0[->X\4]3, &L'^
8_JA% (#`)3*a IAHb?R@, 8cB?*a d+?
, &e,R@c-.#$% / #, ;7
*6fLGGPP"g(GGPS)"h0 12PH, 934ij4"k5g l6m3BbH, 9A@7n*a d+3oGp8&
9L :qp% rj3s tu.v%
1. +,-./01234"56%78 9:;<
GGPP, ;7*6wS*T;U(x7-.
7*6yz7;L{&|PH<=(
#"IA% PRP, \z}~~3>"OGGPS STz, <=G#LD-(>3cO?
8? IAHbp% 9?#?A@l6m@LdA
b, GGPS^BC68sF<=(GGPS1, GGPS3, GGPS9),DE(GGPS2, GGPS4),-(>(GGPS6)3
O?+@R3Pp% L, \z}~~#
;7*6L{!""3F.L|GGPPs
*V.#G3PHb?8@Ap H1%
90IJK3, LZ3bH<=*(/(-*(
+(MEP)PpIPPῌDMAPP"Mh087IA , 3bHc?MEPh0"O8? IAq p% NO\z}~~MEPh0#PDSTzl6m Q*%P, ?A8R!c3;U(&
#$ent-kaureneSTU8V???#,
/h08\z}~<=(#GGPP34h0#
$?+@R3Pp% Jp, E<z+h0#
DMAPP"3IPP:!g(IPI)8FW#$8,MEPh 0XY#IPPDMAPP8Z[3IApq, MEPh 0#IPIP\+#$p% NO, \z}~~3 2"OIPI8{@c<=3"O ¡, IPI1]3
E3, IPI2-(>3O?^_q p% I@3IPI-:%P, ?:#<z +R@/7z*MJ`8¢a3Q*IA8, MEP
&£X\X\*z/R@-01z*MJ`¤
¥{¦§GLb?+@R3Pp% L, \z }~~#IPI8MEPh0"O<=#¤¥{F .IALb?8Rp%
2. =>?@ABCDEF3GHIJK
3bcZL{b¨Z8©c, ;7*6w0 [->X\8deIA?rR@f@AHb p% 9"h03BbHGGPPR@2gªE!h
«i]6E!gl6m8ZjIAHbp8,r¬h
«h0kd+ lp% NO, bcZ©c
®X=(\m'¯®z>dA°t n8R5PH, ].L0[->X\±B#$
T.®-"h0K+@R3PpH2%m'
24[²J#h[9¯®z>°t, T.®-
"3kE!gl6m(OsCPS4,OsKSL4)m'
8[²³®±´9L7n?Pp% 9?#, ?A@
l6mZo9L7n?l6mpqPp% µrsb?
3, pqIApl6m]P450+!gl6mtu gl6m, 4vc;OsCPS4OsKSL4¶w3·
3PHl6m®./PHbp% ?A8T.®- 3kx"l6m®./#$?y+
pq, ®./(P450l6m(CYP99A2ῌCYP99A3) RNAiz345Q*P, ?A@8T.®-3FW#$
?+@R3Pp% I@3, "1²³¯.;
de8®./(tugOsMAS34HT.
®-A3NIA?cy+Pp%?A@°tR@,
L1 \z}~~¸{E3GGGPS-GFPE (O%
Q.)*Q.)*-(+"g\z}~~3
bH, <= ¹3, DE ºj, -(
> ¹j 3O%
|»!}~ O¼½.
20
4
P450
!"#$%$#&
'()*+,- .
$#& %/!0123456 7#&89:2;!<=3"=>'
#$#& *+?$@?%&* A ,-
3.
!!"#$%$#& B7CD8 E'(+,- FG $#& )
OsKSL4H0! E* )
I+,&JB%-+ bZIPK./L*+?
0TGAMN$ '1OP(Q,2R3@
,-S13TTGAMN$ '('OsKSL4 4U1OP(TGAMN$ OsKSL4
* 4U5(*6+ 78A,VS$0:J SWXYZ9:;[\- <= Tos17>?@
]E* OsTGAP1*A^,TGAMN$ ' OsKSL44UB=>!"#$%C1OL
=>)*4_+,-OsTGAP1DE 4U`=
-EFG=!"#$%C'ab)* <
' 4c H8d*e OsKSL4 4U*!"#$%C'fRg))*_
<\+,- ( hi )./L4U j k,'(l*Ih- mJK<)*
)4Uk, !"#$%$#&
)nLol_ !"#
$%pqMKMNS%:J4=>MN S%75C*Ye 4Ul NrO,- st? )uvwP=MEPx =Q bRo(y?'4c
)4U'OsTGAP1z{)*lS
+,-p)*Tuv.<?OsTGAP1'4c ,KMNS%:J4C 1O(V& ./L=>)*5()*
'=R, |U3}-
V~ OsTGAP1KMNS%:J4
$#& 4U1OWX E*Y@**l MEPx $#&
pq4UZ(OsTGAP1[B7CD8l +,<- V4_ OsTGAP1DE 4U' S\]^,.<?H#S"X_+ S
`\,(Q,5()*'=R,- )\
I+'a,S()*= aS HJ6S
bC4c)*ld=R- lo
<b+ooe fIF=
uv g+ )F=p)hi4c,@
j+,<-
Tuv uvklmM0:uv&8Nn opqr7|UuPSC} l*=s+,~ t
bx? tbCuuv
vwuuvxyz7{l*8h,l
=> Ul<{<,\<?.F(.|
}7~bO+F(- Z* A, M uvXvwuuvxuvB )F
=j=> <,\RF+,i 7 7|UCu}.¡uvx¢£~¤
+F(- F, SMNS%:J4Co<
? ¥uv8A?.F(y¦b§7
07 teub 7 ¨bp
7Kb¤<,+F(- uPSCy©!
ª« tbCuuv
¬y7 teb7 7 r b p¡}7 r¢®¯°£ ¤¥±¦
²@§b¥uv¨©§Kb¤<,+F(- F , ªNn{A?.F(zb«³
7 ´ ¬7 a7 P®µb¯
°7±7 7²~²©§Kb¤<,+F(- <
~ F+,' T³´<,\RF+,µTe
¶Pt¶· ¬7bO+F(-
!2 SKMNS%:J4x - MEPx x?,GGPP4
¸¹·loº@¸ P450 ,i 14¸MNS
%:J4'-
!3 OsTGAP1 !"#$%$#&
)(y?4U4c ¹ (\= b MEPx º ldoKMNS%:J4MNS%
754Ulh-
