| Company Name: |
Nantong QuanYi Biotechnology Co., Ltd
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| Tel: |
0513-66337626 18051384581 |
| Email: |
sales@chemhifuture.com |
| Products Intro: |
Product Name:AS-99
CAS:2323623-93-2
Purity:98%+ HPLC Package:10mg，500mg，1g，2g，5g，10g，more
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| | 3-Azetidinecarboxamide, N-[[3-[3-(aminothioxomethyl)phenyl]-1-[1-[(trifluoromethyl)sulfonyl]-4-piperidinyl]-1H-indol-6-yl]methyl]-1-methyl- Basic information |
| | 3-Azetidinecarboxamide, N-[[3-[3-(aminothioxomethyl)phenyl]-1-[1-[(trifluoromethyl)sulfonyl]-4-piperidinyl]-1H-indol-6-yl]methyl]-1-methyl- Chemical Properties |
| density | 1.49±0.1 g/cm3(Predicted) | | storage temp. | Store at -20°C | | pka | 12.74±0.29(Predicted) | | form | Solid | | color | Light yellow to yellow |
| | 3-Azetidinecarboxamide, N-[[3-[3-(aminothioxomethyl)phenyl]-1-[1-[(trifluoromethyl)sulfonyl]-4-piperidinyl]-1H-indol-6-yl]methyl]-1-methyl- Usage And Synthesis |
| Biological Activity | AS-99 is a first-in-class, potent and selective ASH1L histone methyltransferase inhibitor (IC50= 0.79 μM, Kd= 0.89 μM) with anti-leukemic activity. AS-99 blocks cell proliferation, induces apoptosis and differentiation, downregulates MLL fusion target genes, and reduces the leukemia burden in vivo[1].
AS-99 is tested against a panel of 20 histone methyltransferases, including NSD1, NSD2, NSD3, and SETD2. NO significant inhibition is observed at 50 μM of AS-99 on any of the tested histone methyltransferases, indicating over 100-fold selectivity towards ASH1L[1].AS-99 shows effect on the growth of the MLL leukemia cells (MV4;11, MOLM13, KOPN8, RS4;11) with the GI50 values ranging from 1.8 μM to 3.6 μM[1].AS-99 (1-8 μM; 7 days) also induces apoptosis in the MLL leukemia cells, but not in the K562 cells, as assessed by the quantification of the Annexin V positive cells[1].AS-99 suppresses MLL fusion driven transcriptional programs[1].
AS-99 (30 mg/kg; i.p.; q.d., treated for 14 consecutive days) reduces leukemia burden in mice[1].AS-99 is used for in vivo studies in mice, which reveals favorable exposure in plasma upon i.v. and i.p. administration (AUC = 9701 hr* ng/mL and 10,699 hr* ng/mL, respectively), suitable half-life (~5-6 h) and Cmax >10 μM[1]. | | References | [1]. David S. Rogawski, Jing Deng, Hao Li, Tomasz Cierpicki, Jolanta Grembecka, et al. Discovery of first-in-class inhibitors of ASH1L histone methyltransferase with anti-leukemic activity. Nat Commun. 2021 May 14;12(1):2792. |
| | 3-Azetidinecarboxamide, N-[[3-[3-(aminothioxomethyl)phenyl]-1-[1-[(trifluoromethyl)sulfonyl]-4-piperidinyl]-1H-indol-6-yl]methyl]-1-methyl- Preparation Products And Raw materials |
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