ABT-199 (Synonyms: GDC 0199, Venetoclax)

Name: ABT-199
Brand: GlpBio
SKU: GC14069
Availability: InStock
Rating: 5 (30 reviews)

カタログ番号GC14069

Bcl-2阻害剤

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ABT-199 化学構造

Cas No.: 1257044-40-8

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10mM (in 1mL DMSO)	$87.00	在庫あり
2mg	$33.00	在庫あり
5mg	$66.00	在庫あり
10mg	$91.00	在庫あり
50mg	$264.00	在庫あり
100mg	$385.00	在庫あり

Tel：(909) 407-4943 Email: sales@glpbio.com

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カスタマーレビューに基づきます。

Sample solution is provided at 25 µL, 10mM.

Product has been cited by 1 publications

Molecules 27.5 (2022): 1607.PMID:35268708

Description Protocol Chemical Properties Product Documents

Product Documents

Quality Control & SDS

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Purity: >98.00%

Protocol

Kinase experiment [1]:
Preparation Method	The affinity of ABT-199 for different subtypes of the Bcl-2 family (Ki or IC50) was determined by competitive fluorescence polarization assays using the following peptide probe/protein pairs: F-BAD (1 nM) and Bcl-XL (6 nM),F-bax (1 nM) and Bcl-2 (10 nM), F-Bax (1 nM) and Bcl-W (40 nM), F-NOxa (2 nM) and McL-1 (40 nM),And the affinity of F-Bax (1 nM) and Bcl-2-A1(15 nM) for Bcl-XL was determined by time-resolved fluorescence resonance energy transfer assays.1 nM Tb labeled anti-His antibody,And ABT-199 were mixed for 30 min at room temperature on Envision microplate reader. Fluorescence values were measured using excitation filters at 340/35 nm and emission filters at 520/525 (F-BAK) and 495/510 nm (anti-His antibody labeled with Tb).
Reaction Conditions	ABT-199 with Bcl-2 for 30 min at RT
Applications	ABT-199 has a subnanomolar affinity for BCL-2 (Ki < 0.010 nM) and bound over three orders of magnitude less avidly to BCL-XL (Ki = 48 nM) and BCL-W (Ki = 245 nM) than to BCL-2.
Cell experiment [2]:
Cell lines	NHL cell lines
Preparation Method	The viability of NHL cell lines was examined after 48 h incubation with increasing concentrations of Navitoclax or ABT-199.
Reaction Conditions	0.01 μM -3.0 μM ABT-199 for 48h
Applications	ABT-199 cell killing was selective and mechanism dependent, BCL2high status is thus a potential predictive marker for sensitivity to ABT-199.
Animal experiment [3]:
Animal models	Female C.B-17 SCID-beige mice
Preparation Method	All xenograft trials were conducted using ten mice per group, and all mice were ear tagged and monitored individually throughout the studies. ABT-199 was formulated for oral dosing in 60% phosal 50 propylene glycol (PG), 30% polyethylene glycol (PEG) 400 and 10% ethanol. ABT-199 was delivered approximately 2 h before bendamustine or bendamustine plus rituximab.
Dosage form	12.5 mg/kg ABT-199 for 60 days
Applications	After a single oral dose of 12.5 mg per kg body weight in xenografts derived from RS4;11 cells (ALL), ABT-199 caused a maximal tumor growth inhibition (TGImax) of 47% and tumor growth delay (TGD) of 26%.
References: [1].Souers AJ, Leverson JD,et,al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013 Feb;19(2):202-8. doi: 10.1038/nm.3048. Epub 2013 Jan 6. PMID: 23291630.

ベネトクラックス（ABT-199、GDC-0199）は、細胞外アッセイにおけるK iが0.01 nMのBcl-2の選択的阻害剤です。 Bcl-XLとBcl-Wに比べて4800倍以上も選択性が高く、McL-1に対する阻害活性はありません。^[1]

ABT-199細胞殺傷作用は選択性があり、機序に依存しており、BCL2高発現状態はABT-199感受性の予測マーカーとなる可能性がある。BIMがBCL2に結合することはABT-199反応と相関し、さらにBIMのノックアウトはABT-199感受性の低下を引き起こすことが示された。B細胞遺伝子の発現は、ABT-199感受性のある骨髄腫で豊富であったが、単一の遺伝子では一貫して感受性と耐性細胞を区別することはできなかった。 ABT-199耐性を持つOCI-AML3細胞株では、CXCL12がCD44ノックダウンによって取り消された初期幹細胞核心転写因子の高いレベルを発現する細胞割合を増加させた。未熟なT-ALLに関連した転写プログラムを示すLOUCY T-ALL細胞株では、高いBCL-2レベルに対応してin vitroおよびin vivoでABT - 199への高い感受性を示した。さらに、ABT-199は異なる化学療法薬剤との相乗的治療効果を示した。ゲノムワイドCRISPRノックアウトスクリーンを実施し、ミトコンドリア翻訳に関与する遺伝子の不活化が耐性AML細胞でABT-199感受性を回復させたことがわかった。リボソームを標的とする抗生物質（テジゾリドおよびドキシサイクリン）によるミトコンドリアタンパク質合成の薬理学的阻害は、効果的にABT-199耐性を克服した。

VU661013は、新規で強力かつ選択的なMCL1阻害剤です。VU661013は、AMLのマウスモデルにおいてABT-199と安全に組み合わせられ、相乗効果を示しました[3]。ABT-199と5-Azaは、in vitroでAML細胞を殺すために協調作用を発揮し、in vivoで組み合わせ治療の抗腫瘍活性を示します[5]。ABT-199単独および併用治療はよく耐容性があり、最も一般的な副作用は好中球減少症、感染症および消化器毒性です[2]。

References:
[1]: Souers AJ, Leverson JD, et,al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013 Feb;19(2):202-8. doi: 10.1038/nm.3048. Epub 2013 Jan 6. PMID: 23291630.
[2]: Ramsey HE, Fischer MA, et,al. A Novel MCL1 Inhibitor Combined with ABT-199 Rescues ABT-199-Resistant Acute Myelogenous Leukemia. Cancer Discov. 2018 Dec;8(12):1566-1581. doi: 10.1158/2159-8290.CD-18-0140. Epub 2018 Sep 5. PMID: 30185627; PMCID: PMC6279595.
[3]: Bi C, Zhang X, et,al. Inhibition of 4EBP phosphorylation mediates the cytotoxic effect of mechanistic target of rapamycin kinase inhibitors in aggressive B-cell lymphomas. Haematologica. 2017 Apr;102(4):755-764. doi: 10.3324/haematol.2016.159160. Epub 2017 Jan 19. PMID: 28104700; PMCID: PMC5395116.
[4]: Gupta VA, Barwick BG, et,al. ABT-199 sensitivity in multiple myeloma is associated with B-cell gene expression. Blood. 2021 Jul 1;137(26):3604-3615. doi: 10.1182/blood.2020007899. PMID: 33649772; PMCID: PMC8462405.
[5]: Jin S, Cojocari D, et,al. 5-Azacitidine Induces NOXA to Prime AML Cells for ABT-199-Mediated Apoptosis. Clin Cancer Res. 2020 Jul 1;26(13):3371-3383. doi: 10.1158/1078-0432.CCR-19-1900. Epub 2020 Feb 13. PMID: 32054729.
[6]: Sharon D, Cathelin S, et,al. Inhibition of mitochondrial translation overcomes ABT-199 resistance in AML through activation of the integrated stress response. Sci Transl Med. 2019 Oct 30;11(516):eaax2863. doi: 10.1126/scitranslmed.aax2863. PMID: 31666400.
[7]: Yu X, Munoz-Sagredo L, et,al. CD44 loss of function sensitizes AML cells to the BCL-2 inhibitor ABT-199 by decreasing CXCL12-driven survival cues. Blood. 2021 Sep 23;138(12):1067-1080. doi: 10.1182/blood.2020006343. PMID: 34115113.

Cas No.	1257044-40-8	SDF
同義語	GDC 0199, Venetoclax
Chemical Name	4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide
Canonical SMILES	CC1(CCC(=C(C1)C2=CC=C(C=C2)Cl)CN3CCN(CC3)C4=CC(=C(C=C4)C(=O)NS(=O)(=O)C5=CC(=C(C=C5)NCC6CCOCC6)[N+](=O)[O-])OC7=CN=C8C(=C7)C=CN8)C
Formula	C₄₅H₅₀ClN₇O₇S	M.Wt	868.44
溶解度	≥ 43.422mg/mL in DMSO	Storage	Store at -20°C
General tips	Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition	Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
		1 mg	5 mg	10 mg
	1 mM	1.1515 mL	5.7575 mL	11.5149 mL
	5 mM	0.2303 mL	1.1515 mL	2.303 mL
	10 mM	0.1151 mL	0.5757 mL	1.1515 mL

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

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ABT-199 (Synonyms: GDC 0199, Venetoclax)

顧客レビュー

GlpBio Citations

Bioactive Compounds Premium Provider

Product has been cited by 1 publications

Product Documents

Quality Control & SDS

Protocol

Complete Stock Solution Preparation Table

モルアリティ計算機

希釈計算機

In vivo Formulation Calculator (Clear solution)

レビュー

ABT-199 (Synonyms: GDC 0199, Venetoclax)

顧客レビュー

GlpBio Citations

Bioactive Compounds Premium Provider

Product has been cited by 1 publications

Product Documents

Quality Control & SDS

Protocol

Complete Stock Solution Preparation Table

モルアリティ計算機

希釈計算機

In vivo Formulation Calculator (Clear solution)

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