Nature - USA (2020-09-24)

Article

-1 01

0.0

0.4

0.8

1.2

Relative

viabilit

y

-1 01

0.0

0.4

0.8

1.2

Relative

viabilit

y

-2 -1 0

shNC

FAR1-sh1

FAR1-sh2

FAR1-sh3

FAR1-sh4

786-O

-2 -1 0

shNC

GNPAT-sh 1

GNPAT-sh 2

GNPAT-sh 3

GNPAT-sh 4

786-O

Log 10 (M ML210) Log 10 (μM RSL3)

e f

123

0.0

0.4

0.8

1.2

Log 10 (M compound)

%D

PPHr

emainin

g

ZINC-69435460

Fer-1

DPPHassay

-1 01

AGPS-sg 2

AGPS-sg2+mAgps

Log 10 (M RSL3)

75 OVCAR-8

50

37

MW(KDa)

sgNC

AGPS-sg 2

mAgps

++– –

++

• – ++

––

AGPS

β-ACTIN

g

b

i

a

Log 10 (M ML210) Log 10 (M RSL3)

-2 -1 01

0.0

0.4

0.8

1.2

-3 -2 -1 0

sgNC

SOD1-sg1

SOD1-sg2

SOD1-sg3

CAT-sg1

CAT-sg2

Log 10 (M ML210) Log 10 (M RSL3)

Relative

viabilit

y

786-O-Cas9 786-O-Cas9

sg-C AT

MW(KDa) sgNCsg1sg2

50

Catalase

37

ns

50

37

β-ACTIN

75

50

37

β-ACTIN

25

20

SOD1

MW(KDa) sgNCsg1sg2 sg3

sg-SOD1

j k

-1 01

0.0

0.4

0.8

1.2

Log 10 (M ML210)

OVCAR-8

-1 01

Vector

mAgps

mFar1

mPex3

mPex10

Log 10 (M RSL3)

OVCAR- 8

Relative viabilit

y

d

-1 01

0.0

0.4

0.8

1.2

Log 10 (M ML210)

Relative viabilit

y

-1 01

0.0

0.5

1.0

1.5

Log 10 (M ML210)

Relative viabilit

y

[ML210], μM

[ZINC], M

ZINC-69435460

0

25

50

75

100

125

%

Viability

OVCAR-8

0

150

250

350

500

0.00 0.20 0.250.35

h

-2 -1 01

FAR1-sg2

FAR1-sg2+mFar1

Log 10 (M RSL3)

c OVCAR-8

Extended Data Fig. 5 | See next page for caption.