3-Azetidinecarboxamide, N-[[3-[3-(aminothioxomethyl)phenyl]-1-[1-[(trifluoromethyl)sulfonyl]-4-piperidinyl]-1H-indol-6-yl]methyl]-1-methyl-
![3-Azetidinecarboxamide, N-[[3-[3-(aminothioxomethyl)phenyl]-1-[1-[(trifluoromethyl)sulfonyl]-4-piperidinyl]-1H-indol-6-yl]methyl]-1-methyl- Structure](CAS/20210305/GIF/2323623-93-2.gif)
- CAS No.
- 2323623-93-2
- Chemical Name:
- 3-Azetidinecarboxamide, N-[[3-[3-(aminothioxomethyl)phenyl]-1-[1-[(trifluoromethyl)sulfonyl]-4-piperidinyl]-1H-indol-6-yl]methyl]-1-methyl-
- Synonyms
- AS-99 TFA;AS-99 free base;ASH1L inhibitor AS-99;AS99 free base,AS 99 free base;3-Azetidinecarboxamide, N-[[3-[3-(aminothioxomethyl)phenyl]-1-[1-[(trifluoromethyl)sulfonyl]-4-piperidinyl]-1H-indol-6-yl]methyl]-1-methyl-
- CBNumber:
- CB29042247
- Molecular Formula:
- C27H30F3N5O3S2
- Molecular Weight:
- 593.68
- MDL Number:
- MFCD34473328
- MOL File:
- 2323623-93-2.mol
3-Azetidinecarboxamide, N-[[3-[3-(aminothioxomethyl)phenyl]-1-[1-[(trifluoromethyl)sulfonyl]-4-piperidinyl]-1H-indol-6-yl]methyl]-1-methyl- Chemical Properties,Uses,Production
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
Raw materials
Preparation Products
3-Azetidinecarboxamide, N-[[3-[3-(aminothioxomethyl)phenyl]-1-[1-[(trifluoromethyl)sulfonyl]-4-piperidinyl]-1H-indol-6-yl]methyl]-1-methyl- Suppliers
| Supplier | Tel | Country | ProdList | Advantage | |
|---|---|---|---|---|---|
| Suzhou youruike Chemical Pharmaceutical Technology Co., Ltd | 15317229551 | 15151849396@163.com | China | 994 | 58 |
| Block Chemical Technology (Shanghai) Co., LTD | 021-20432219 13918097649 | li_jinfei@acblock-lab.com | China | 9964 | 58 |
| TargetMol Chemicals Inc. | 4008200310 | marketing@tsbiochem.com | China | 23963 | 58 |
| Nantong QuanYi Biotechnology Co., Ltd | 0513-66337626 18051384581 | sales@chemhifuture.com | China | 4578 | 58 |