AS-99TFA
PRODUCTS SPECIFICATIONS
DESCRIPTION
Overview
| MDL | - |
|---|---|
| Molecular Weight | 707.71 |
| Molecular Formula | C29H31F6N5O5S2 |
| 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.O=C(O)C(F)(F)F |
Summary
AS-99 TFA is a first-in-class, potent and selective ASH1L histone methyltransferase inhibitor ( IC 50 = 0.79 µM, K d = 0.89 µM) with anti-leukemic activity. AS-99 TFA 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 TFA 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 TFA 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) TFA 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 TFA 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) TFA reduces leukemia burden in mice
[1]
.
AS-99 TFA 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. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
DMSO : 100 mg/mL ( 141.30 mM ; Need ultrasonic)
H 2 O : 12.5 mg/mL ( 17.66 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.4130 mL | 7.0650 mL | 14.1301 mL |
| 5 mM | 0.2826 mL | 1.4130 mL | 2.8260 mL |
| 10 mM | 0.1413 mL | 0.7065 mL | 1.4130 mL |
-
1.
Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)
Solubility: 2.5 mg/mL (3.53 mM); Clear solution; Need ultrasonic
-
2.
