2653994-10-4

2653994-10-4 structure

2653994-10-4 structure

Name: (S)-JDQ-443
Chemical Name: (S)-JDQ-443
CAS Number: 2653994-10-4
Molecular Formula: C₂₉H₂₈ClN₇O
Molecular Weight: 526.03
Catalog: Signaling Pathways Cell Cycle/DNA Damage PERK
Create Date: 2023-04-05 05:55:09
Modify Date: 2024-01-16 23:05:38
(S)-JDQ-443 is an isomer of JDQ-443 (HY-139612). JDQ-443 is an orally active, potent, selective, and covalent KRAS G12C inhibitor (extracted from patent WO2021120890A1). JDQ-443 shows antitumor activity[1][2].

Name	(S)-JDQ-443

Description	(S)-JDQ-443 is an isomer of JDQ-443 (HY-139612). JDQ-443 is an orally active, potent, selective, and covalent KRAS G12C inhibitor (extracted from patent WO2021120890A1). JDQ-443 shows antitumor activity[1][2].
Related Catalog	Research Areas >> Cancer Signaling Pathways >> GPCR/G Protein >> Ras Signaling Pathways >> Cell Cycle/DNA Damage >> PERK
In Vitro	JDQ-443 促进磷酸化ERK（pERK）水平的剂量依赖性降低，并促进 KRASG12C 突变细胞系 NCI-H358 和 NCI-H2122 的增殖，其 IC50值分别为 0.018 和 0.063 μM[2]。 JDQ443 与 GDP结合的 KRASG12C 共价且选择性地结合并抑制其与 RAS 开关 II 口袋的低可逆结合亲和力，还能抑制KRASG12C突变和 KRAS G12C/H95、G12C/R68S 和 G12C/Y96 双突变细胞系的增殖[2]。
In Vivo	JDQ443（10-100 mg/kg，口服，每天，14天）显示出抗肿瘤活性，并以剂量依赖的方式抑制 KRAS G12C 突变的 CDX 模型的肿瘤生长[2]。 JDQ443（口服，100 mg/kg，每日（JDQ443）+7.5mg/kg，每日两次（TNO155），共36天）与单药 JDQ443 联合使用时，显示出更大的细胞生长抑制或细胞杀死作用[2]。 JDQ443 在 NSCLC 和结直肠肿瘤的 PDX 模型中产生了分类抗肿瘤反应，并通过与其他药物的联合治疗得到改善[2]。
References	[1]. LIU BO, et al. PYRAZOLYL DERIVATIVES USEFUL AS ANTI-CANCER AGENTS. Patent WO2021120890A1. [2]. Weiss A, Lorthiois E, Barys L, et al. Discovery, Preclinical Characterization, and Early Clinical Activity of JDQ443, a Structurally Novel, Potent and Selective, Covalent Oral Inhibitor of KRASG12C. Cancer Discov. 2022;candisc.0158.2022.

Molecular Formula	C₂₉H₂₈ClN₇O
Molecular Weight	526.03