ARS-1620

製品コードS8707 バッチS870705

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder

化学式

C₂₁H₁₇ClF₂N₄O₂

分子量

430.84

CAS No.

1698055-85-4

Solubility (25°C)*

体外

DMSO

86 mg/mL (199.61 mM)

Ethanol

5 mg/mL (11.6 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension

CMC-NA

≥5mg/ml

Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	ARS-1620 is a potent, orally bioavailable covalent inhibitor of KRAS^G12C) and could achieve rapid and sustained in vivo target occupancy to induce tumor regression.
in vitro	ARS-1620 covalently inhibits KRAS (G12C) activity with high potency and atropisomeric selectivity in p.G12C mutant cancer cells. This compound rapidly engaged G12C in a concentration- and time- dependent manner consistent with its covalent mechanism of inhibition. Across a panel of cell lines harboring the mutant allele, it exhibited a half maximal G12C target engagement (TE50) at ~0.3 μM and near complete engagement at 3.0 μM after 2 hr of treatment. This chemical inhibits RAS-GTP and the phosphorylation of MEK, ERK, RSK, S6, and AKT in a dose-dependent and selective manner in H358 (p.G12C) but not in negative control lung cancer cell lines lacking p.G12C (A549, H460, and H441). It elicits sub-micromolar allele-specific potency (IC50 = 0.3 μM; IC90 = 1 μM). The activity of this compound is specific to the G12C allele and mediated by the covalent modification of Cys-12^[1].
in vivo	ARS-1620 exhibits excellent oral bioavailability (F > 60%) in mice. In MIA-PaCa2 xenografts (p.G12C), this compound significantly inhibits tumor growth (p < 0.001) in a dose-dependent manner with marked regression at a dose of 200 mg/kg, given once daily. Xenografts of H441 (p.G12V) lack a response at all doses tested and the R-atropisomer of this chemical lacks activity in both models. It selectively induces tumor regression in patient-derived tumor models (harboring KRAS p.G12C)^[1].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	H358 cells
	濃度	4 μM
	反応時間	4 h
	実験の流れ	Cells are maintained in a humidified incubator at 37 C with 5% CO2, and grown in RPMI 1640 or DMEM supplemented with 10% FBS and 50 IU ml-1 penicillin/streptomycin.
動物実験	動物モデル	6- to 8-week-old male BALB/c mice
	投薬量	2 and 10 mg/kg
	投与方法	intravenous (IV) bolus or oral gavage administration

参考

https://pubmed.ncbi.nlm.nih.gov/29373830/

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

CETSA-MS unveils novel targets engaged by rigosertib to promote anti-tumor activity and inflammatory responses [ iScience, 2025, 28(6):112748]	PubMed: 40585507
ERK signaling promotes IKKε expression and oncogenic functions in pancreatic cancer cells in association with TBK1 [ J Biol Chem, 2025, S0021-9258(25)02386-5]	PubMed: 40738190
Multifactorial stroma-mediated resistance is a major contributor to residual disease under targeted therapies in lung cancers [ Res Sq, 2025, rs.3.rs-6264377]	PubMed: 40313737
Focal adhesion kinase-YAP signaling axis drives drug-tolerant persister cells and residual disease in lung cancer [ Nat Commun, 2024, 15(1):3741]	PubMed: 38702301
Hedgehog signalling is involved in acquired resistance to KRASG12C inhibitors in lung cancer cells [ Cell Death Dis, 2024, 15(1):56]	PubMed: 38225225
YAP/TAZ mediates resistance to KRAS inhibitors through inhibiting proapoptosis and activating the SLC7A5/mTOR axis [ JCI Insight, 2024, 9(24)e178535]	PubMed: 39704172
Tumor Cell Spatial Organization Directs EGFR/RAS/RAF Pathway Primary Therapy Resistance through YAP Signaling [ bioRxiv, 2024, 2024.09.26.615226]	PubMed: 39386679
Therapy-induced APOBEC3A drives evolution of persistent cancer cells [ Nature, 2023, 620(7973):393-401]	PubMed: 37407818
Multiscale Analysis and Validation of Effective Drug Combinations Targeting Driver KRAS Mutations in Non-Small Cell Lung Cancer [ Int J Mol Sci, 2023, 24(2)997]	PubMed: 36674513
Oncogenic KRAS promotes pancreatic ductal adenocarcinoma (PDAC) through post-transcriptionally regulated KRAS-induced granules (KGs) [ Research Square, 2023, 10.21203/rs.3.rs-3064215/v1]	PubMed: None

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。