2502156-03-6

中文名称 PROTAC KRASG12C Degrader-LC-2

英文名称 PROTAC KRASG12C Degrader-LC-2

CAS 2502156-03-6

更新日期 2023/09/12 11:59:19

分子式 C59H71ClFN11O7S

分子量 1132.78

2502156-03-6 结构式

基本信息物理化学性质安全数据 PROTAC KRASG12C Degrader-LC-2价格(试剂级) 常见问题列表

基本信息

中文别名

(2S,4R)-1-((S)-2-(3-(3-((S)-2-(((7-(8-氯萘-1-基)-4-((S)-3-(氰基甲基)-4-(2-氟丙烯酰基)哌嗪-1-基)-5,6,7,8-四氢吡啶并[3,4-D]嘧啶-2-基)氧基)甲基)吡咯烷-1- 基)丙氧基)丙酰胺基)-3,3-二甲基丁酰基)-4-羟基-N-(4-(4-甲基噻唑-5-基)苄基)吡咯烷-2-甲酰胺

英文别名

LC-2
PROTAC KRASG12C Degrader-LC-2
(2S,4R)-1-((S)-2-(3-(3-((S)-2-(((7-(8-Chloronaphthalen-1-yl)-4-((S)-3-(cyanomethyl)-4-(2-fluoroacryloyl)piperazin-1-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)oxy)methyl)pyrrolidin-1-yl)propoxy)propanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-m
(2S,4R)-1-((S)-2-(3-(3-((S)-2-(((7-(8-Chloronaphthalen-1-yl)-4-((S)-3-(cyanomethyl)-4-(2-fluoroacryloyl)piperazin-1-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)oxy)methyl)pyrrolidin-1-yl)propoxy)propanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide

物理化学性质

密度1.297±0.06 g/cm3(Predicted)

储存条件-20°C储存

溶解度DMSO: 50 mg/mL (44.14 mM; ultrasonic and warming and heat to 80°C)

酸度系数(pKa)14.07±0.40(Predicted)

形态Solid

颜色Off-white to brown

安全数据

危险性符号(GHS)

GHS07

警示词警告

危险性描述H302-H315-H319-H335

防范说明P261-P305+P351+P338

PROTAC KRASG12C Degrader-LC-2价格(试剂级)

报价日期	产品编号	产品名称	CAS号	包装	价格
2024/04/30	HY-137516	(2S,4R)-1-((S)-2-(3-(3-((S)-2-(((7-(8-氯萘-1-基)-4-((S)-3-(氰基甲基)-4-(2-氟丙烯酰基)哌嗪-1-基)-5,6,7,8-四氢吡啶并[3,4-D]嘧啶-2-基)氧基)甲基)吡咯烷-1- 基)丙氧基)丙酰胺基)-3,3-二甲基丁酰基)-4-羟基-N-(4-(4-甲基噻唑-5-基)苄基)吡咯烷-2-甲酰胺 LC-2	2502156-03-6	1mg	3200元
2024/04/30	HY-137516	(2S,4R)-1-((S)-2-(3-(3-((S)-2-(((7-(8-氯萘-1-基)-4-((S)-3-(氰基甲基)-4-(2-氟丙烯酰基)哌嗪-1-基)-5,6,7,8-四氢吡啶并[3,4-D]嘧啶-2-基)氧基)甲基)吡咯烷-1- 基)丙氧基)丙酰胺基)-3,3-二甲基丁酰基)-4-羟基-N-(4-(4-甲基噻唑-5-基)苄基)吡咯烷-2-甲酰胺 LC-2	2502156-03-6	5mg	9800元
2022/09/18	HY-137516	(2S,4R)-1-((S)-2-(3-(3-((S)-2-(((7-(8-氯萘-1-基)-4-((S)-3-(氰基甲基)-4-(2-氟丙烯酰基)哌嗪-1-基)-5,6,7,8-四氢吡啶并[3,4-D]嘧啶-2-基)氧基)甲基)吡咯烷-1- 基)丙氧基)丙酰胺基)-3,3-二甲基丁酰基)-4-羟基-N-(4-(4-甲基噻唑-5-基)苄基)吡咯烷-2-甲酰胺 LC-2	2502156-03-6	10mg	25000元

常见问题列表

生物活性

LC-2 是首创的内源性 KRAS G12C 的 PROTAC 降解剂，DC50 在 0.25 和 0.76 μM 之间。LC-2 是一种 PROTAC，与 MRTX849 共价结合 KRAS G12C 并招募 E3 连接酶 VHL，诱导 KRAS G12C 快速持续降解，导致纯合和杂合子 KRAS G12C 细胞系 MAPK 信号的抑制。

靶点

KRAS(G12C)

0.25-0.76 μM (DC ₅₀ )

VHL

体外研究

LC-2 induces degradation of endogenous KRASG12C in multiple KRAS mutant cancer cell (NCI-H2030, MIA PaCa-2, SW1573, NCI-H23 and NCI-H358 cells) with DC ₅₀ s between 0.25 and 0.76 μM. LC-2-induced KRASG12C degradation occurs via a bona fide PROTAC mechanism. MIA PaCa-2, NCI-H23, and SW1573 cells are treated with 2.5 μM of LC-2 for 6, 24, 48, and 72 h. In all three cell lines, maximal KRAS degradation occurred within 24 h and was sustained up to 72 h.
LC-2-induced (2.5 μM; 6-24 hours) KRAS G12C degradation modulates Erk signaling in homozygous and heterozygous KRAS mutant cell lines.

Western Blot Analysis

Cell Line:	MIA PaCa-2 cells and NCI-H23 cells
Concentration:	2.5 μM
Incubation Time:	6-24 hours
Result:	Inhibition and degradation of KRAS G12C decreases pErk signaling at 6 and 24 h in homozygous MIA PaCa-2 cells