1. Epigenetics
    Apoptosis
  2. Histone Methyltransferase
    Apoptosis
  3. AS-99

AS-99 

Cat. No.: HY-141429C
Handling Instructions

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.

For research use only. We do not sell to patients.

AS-99 Chemical Structure

AS-99 Chemical Structure

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Description

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].

IC50 & Target

0.79 µM (ASH1L histone methyltransferase)[1]

In Vitro

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 a several fold weaker effect on the proliferation of leukemia cells without MLL1 translocations, such as SET2 and K562, with no or limited effects at 10 µM or higher concentrations[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 results in a reduced number of H3K36me2 peaks when compared to the DMSO-treated cells[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

RT-PCR[1]

Cell Line: MOLM13 cells
Concentration: 2-6 µM
Incubation Time: 7 days
Result: Led to a dose-dependent downregulation of canonical MLL fusion target genes required for leukemogenesis including MEF2C, DLX2, FLT3, and HOXA9.
In Vivo

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: 8- to 10-week old female NSG mice (bearing MV4;11 cells)[1]
Dosage: 30 mg/kg
Administration: I.p.; q.d., treated for 14 consecutive days
Result: Reduced the leukemia burden in the xenotransplantation mouse model of MLL leukemia without affecting blood counts in normal mice.
Molecular Weight

630.14

Formula

C27H31ClF3N5O3S2

SMILES

O=C(C1CN(C)C1)NCC2=CC3=C(C=C2)C(C4=CC=CC(C(N)=S)=C4)=CN3C5CCN(S(=O)(C(F)(F)F)=O)CC5.[H]Cl

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation
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