| Chemical Properties | Back Directory | [density ]
1.49±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted) | [storage temp. ]
-10 to -25°C | [solubility ]
DMSO: 2mg/mL, clear | [form ]
Solid | [pka]
1.66±0.10(predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [Description]
AK-2292 is a potent and highly selective STAT5 PROTAC degrader. AK-2292 induces STAT5A/B protein degradation in vitro and in vivo, as well as excellent selectivity for all other STAT proteins and more than 6,000 non-STAT proteins, resulting in the selective inhibition of STAT5 activity in the cell. AK-2292 effectively induces STAT5 degradation in normal mouse tissues and human chronic myeloid leukaemia (CML) mouse xenografts. It also effectively inhibits the growth of acute myeloid leukaemia (AML) cell lines. | [Chemical Properties]
Off-white to light yellow Solid | [Uses]
AK-2292 is a potent and selective STAT5 PROTAC degrader, with a DC50 of 0.10 μM. AK-2292 induces degradation of STAT5A/B proteins in vitro and in vivo. AK-2292 can induce tumor regression in acute myeloid leukemia and chronic myeloid leukemia xenograft mouse models[1][2]. AK-2292 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups. | [in vivo]
AK-2292 (50-200 mg/kg; i.p. once a day, 5 days a week for 3 weeks) inhibits tumor growth in the MV4;11 xenograft model in mice[1].
AK-2292 (150 mg/kg; a single i.p.) induces rapid and >95% depletion of STAT5 and pSTAT5Y694 proteins in the MV4;11 xenograft tissues in mice[1].
AK-2292 (i.p.) exhibits good plasma exposure and has a plasma half-life of 1.9 h, moderate clearance (CL=0.77 L/h/kg), and good volume distribution (Vz=2.1 L/kg)[1]. | Animal Model: | SCID mice bearing MV4;11 tumors[1] | | Dosage: | 50, 100, 200 mg/kg | | Administration: | I.p. injection, once a day, 5 days per week for 3 weeks | | Result: | Inhibited tumor growth in a dose-dependent manner and achieved 50, 60, and 80% of tumor growth inhibition at doses of 50, 100, and 200 mg/kg, respectively.
Did not induce animal weight loss or any other signs of toxicity.
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| [IC 50]
STAT5: 0.10 μM (DC50) | [References]
[1] Kaneshige A, et, al. Discovery of a Potent and Selective STAT5 PROTAC Degrader with Strong Antitumor Activity In Vivo in Acute Myeloid Leukemia. J Med Chem. 2023 Feb 3. DOI:10.1021/acs.jmedchem.2c01665
[2] Kaneshige A, et, al. A selective small-molecule STAT5 PROTAC degrader capable of achieving tumor regression in vivo. Nat Chem Biol. 2023 Feb 2. DOI:10.1038/s41589-022-01248-4 |
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| Company Name: |
Merck KGaA
|
| Tel: |
21-20338288 |
| Website: |
www.sigmaaldrich.cn |
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