Figure 5 from Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers Article Swipe

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Jingjing Jiang , Lingyan Jiang , Benjamin J. Maldonato , Yingyun Wang , Matthew Holderfield , Ida Aronchik , Ian P. Winters , Zeena Salman , Cristina Blaj , Marie Ménard , Jens Brodbeck , Zhe Chen , Xing Wei , Michael Rosen , Yevgeniy Gindin , Bianca J. Lee , James W. Evans , Stephanie Chang , Zhican Wang , Kyle J. Seamon , Dylan Parsons , James Cregg , Abby Marquez , Aidan C.A. Tomlinson , Jason K. Yano , John E. Knox , Elsa Quintana , Andrew J. Aguirre , Kathryn C. Arbour , Abby Reed , W. Clay Gustafson , Adrian L. Gill , Elena S. Koltun , David Wildes , Jacqueline A.M. Smith , Zhengping Wang , Mallika Singh ·

YOU? · · 2025 · Open Access · · DOI: https://doi.org/10.1158/2159-8290.30062246

Effects of RMC-6236 mediated pharmacologic modulation of RAS pathway signaling in tumor-bearing mice. A, PK/PD relationship between RMC-6236 concentration and inhibition of DUSP6 expression in Capan-2 (EC₅₀ = 90 nmol/L and EC₉₀ = 809 nmol/L), NCI-H441 (EC₅₀ = 117 nmol/L and EC₉₀ = 1,121 nmol/L), and HPAC (EC₅₀ = 135 nmol/L and EC₉₀ = 925 nmol/L) xenograft tumors. Subcutaneous xenograft tumors were treated with vehicle or RMC-6236 ranging from 0.3 to 100 mg/kg (Capan-2 and H441) or to 50 mg/kg (HPAC). B, PK/PD relationship between RMC-6236 concentration and inhibition of Dusp6 expression in ear skin (EC₅₀ = 1,164 nmol/L and EC₉₀ = 10,279 nmol/L) isolated from tumor-bearing BALB/c nude mice treated with vehicle or RMC-6236 ranging from 3 mg/kg to 100 mg/kg. A and B, Tumors and ear skin from tumor-bearing BALB/c nude mice were harvested at indicated time points (n = 3/timepoint/dose). A 3-parameter sigmoidal exposure–response model was fitted to the data to derive EC₅₀ and EC₉₀ values. Time points are represented by colors and doses are represented by symbol shapes. C–G, Histopathology of tumors and ear skin from the Capan-2 xenograft model collected at indicated time points post a single dose of vehicle control, RMC-6236 at 25 mg/kg or 7 consecutive daily doses of RMC-6236 at 25 mg/kg (n = 3–6/time point/dose). Staining of indicated markers in the tumor area or ear skin was quantified and compared with vehicle using one-way ANOVA followed by the Dunnett multiple comparison test (*, P < 0.05; **, P < 0.01; ***, P < 0.001). Representative images are shown at 200× magnification from samples closest to the mean of the respective groups. Scale bar, 50 µm.

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Medicine

Chemistry

Biochemistry

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GTP' Cancer research Medicine Chemistry Biochemistry Enzyme

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Landing Page: https://doi.org/10.1158/2159-8290.30062246
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OpenAlex ID: https://openalex.org/W4414021241

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Title: Figure 5 from Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers

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Authors: Jingjing Jiang, Lingyan Jiang, Benjamin J. Maldonato, Yingyun Wang, Matthew Holderfield, Ida Aronchik, Ian P. Winters, Zeena Salman, Cristina Blaj, Marie Ménard, Jens Brodbeck, Zhe Chen, Xing Wei, Michael Rosen, Yevgeniy Gindin, Bianca J. Lee, James W. Evans, Stephanie Chang, Zhican Wang, Kyle J. Seamon, Dylan Parsons, James Cregg, Abby Marquez, Aidan C.A. Tomlinson, Jason K. Yano, John E. Knox, Elsa Quintana, Andrew J. Aguirre, Kathryn C. Arbour, Abby Reed, W. Clay Gustafson, Adrian L. Gill, Elena S. Koltun, David Wildes, Jacqueline A.M. Smith, Zhengping Wang, Mallika Singh

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Concepts: GTP', Cancer research, Medicine, Chemistry, Biochemistry, Enzyme

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abstract_inverted_index.90	28
abstract_inverted_index.at	136, 185, 197, 207, 257
abstract_inverted_index.by	163, 169, 235
abstract_inverted_index.in	10, 24, 92, 218
abstract_inverted_index.of	1, 6, 21, 89, 174, 193, 205, 215, 266
abstract_inverted_index.or	65, 76, 113, 200, 222
abstract_inverted_index.to	70, 77, 119, 150, 153, 263
abstract_inverted_index.(*,	241
abstract_inverted_index.**,	245
abstract_inverted_index.0.3	69
abstract_inverted_index.100	71, 120
abstract_inverted_index.117	38
abstract_inverted_index.135	49
abstract_inverted_index.809	33
abstract_inverted_index.925	54
abstract_inverted_index.RAS	7
abstract_inverted_index.and	19, 30, 40, 45, 51, 74, 87, 99, 123, 126, 156, 165, 176, 227
abstract_inverted_index.are	161, 167, 255
abstract_inverted_index.ear	93, 127, 177, 223
abstract_inverted_index.the	151, 180, 219, 236, 264, 267
abstract_inverted_index.was	148, 225
abstract_inverted_index.<	243, 247, 251
abstract_inverted_index.***,	249
abstract_inverted_index.HPAC	46
abstract_inverted_index.Time	159
abstract_inverted_index.area	221
abstract_inverted_index.bar,	271
abstract_inverted_index.data	152
abstract_inverted_index.dose	192
abstract_inverted_index.from	68, 105, 116, 129, 179, 260
abstract_inverted_index.mean	265
abstract_inverted_index.mice	109, 133
abstract_inverted_index.nude	108, 132
abstract_inverted_index.post	189
abstract_inverted_index.skin	94, 128, 178, 224
abstract_inverted_index.test	240
abstract_inverted_index.time	138, 187
abstract_inverted_index.were	61, 134
abstract_inverted_index.with	63, 111, 229
abstract_inverted_index.0.01;	248
abstract_inverted_index.0.05;	244
abstract_inverted_index.1,121	43
abstract_inverted_index.1,164	97
abstract_inverted_index.200×	258
abstract_inverted_index.ANOVA	233
abstract_inverted_index.H441)	75
abstract_inverted_index.PK/PD	14, 82
abstract_inverted_index.Scale	270
abstract_inverted_index.daily	203
abstract_inverted_index.doses	166, 204
abstract_inverted_index.mg/kg	72, 79, 118, 199, 209
abstract_inverted_index.mice.	12
abstract_inverted_index.model	147, 183
abstract_inverted_index.shown	256
abstract_inverted_index.tumor	220
abstract_inverted_index.using	231
abstract_inverted_index.10,279	102
abstract_inverted_index.BALB/c	107, 131
abstract_inverted_index.Tumors	125
abstract_inverted_index.colors	164
abstract_inverted_index.derive	154
abstract_inverted_index.fitted	149
abstract_inverted_index.images	254
abstract_inverted_index.mg/kg.	121
abstract_inverted_index.nmol/L	29, 39, 50, 98
abstract_inverted_index.points	139, 160, 188
abstract_inverted_index.single	191
abstract_inverted_index.symbol	170
abstract_inverted_index.tumors	60, 175
abstract_inverted_index.(HPAC).	80
abstract_inverted_index.0.001).	252
abstract_inverted_index.Capan-2	25, 181
abstract_inverted_index.Dunnett	237
abstract_inverted_index.between	16, 84
abstract_inverted_index.closest	262
abstract_inverted_index.groups.	269
abstract_inverted_index.markers	217
abstract_inverted_index.nmol/L)	55, 103
abstract_inverted_index.one-way	232
abstract_inverted_index.pathway	8
abstract_inverted_index.ranging	67, 115
abstract_inverted_index.samples	261
abstract_inverted_index.shapes.	171
abstract_inverted_index.treated	62, 110
abstract_inverted_index.tumors.	57
abstract_inverted_index.values.	158
abstract_inverted_index.vehicle	64, 112, 194, 230
abstract_inverted_index.(Capan-2	73
abstract_inverted_index.NCI-H441	35
abstract_inverted_index.RMC-6236	2, 17, 66, 85, 114, 196, 206
abstract_inverted_index.Staining	214
abstract_inverted_index.compared	228
abstract_inverted_index.control,	195
abstract_inverted_index.followed	234
abstract_inverted_index.isolated	104
abstract_inverted_index.mediated	3
abstract_inverted_index.multiple	238
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abstract_inverted_index.harvested	135
abstract_inverted_index.indicated	137, 186, 216
abstract_inverted_index.sigmoidal	145
abstract_inverted_index.signaling	9
abstract_inverted_index.xenograft	56, 59, 182
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abstract_inverted_index.inhibition	20, 88
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abstract_inverted_index.respective	268
abstract_inverted_index.3-parameter	144
abstract_inverted_index.consecutive	202
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abstract_inverted_index.point/dose).	213
abstract_inverted_index.relationship	15, 83
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abstract_inverted_index.pharmacologic	4
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abstract_inverted_index.µm.</p>	273
abstract_inverted_index.<p>Effects	0
abstract_inverted_index.3/timepoint/dose).	142
abstract_inverted_index.exposure–response	146
abstract_inverted_index.<b>A</b>	122
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abstract_inverted_index.<b>B,</b>	81, 124
abstract_inverted_index.(<i>n</i>	140, 210
abstract_inverted_index.<i>DUSP6</i>	22
abstract_inverted_index.<i>Dusp6</i>	90
abstract_inverted_index.<b>C–G,</b>	172
abstract_inverted_index.EC<sub>50</sub>	155
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abstract_inverted_index.(EC<sub>50</sub>	26, 36, 47, 95
cited_by_percentile_year
countries_distinct_count	0
institutions_distinct_count	37
citation_normalized_percentile.value	0.37389511
citation_normalized_percentile.is_in_top_1_percent	False
citation_normalized_percentile.is_in_top_10_percent	False