SEL24-B489

Research use only, not for human use.

SEL24-B489 (SEL24) is a potent, dual PIM and FLT3-ITD inhibitor.

SEL24-B489 (SEL24) is a potent, dual PIM and FLT3-ITD inhibitor with Kd of 2/2/3 nM for PIM1/2/3, Kd of 160/16 nM for FLT3-WT/FLT3-ITD, respectively; exhibits significantly broader on-target activity in AML cell lines (MV-4-11 GI50=20 nM) and primary AML blasts than selective FLT3-ITD or PIM inhibitors, decreases viability of AML cells with FLT3-TKD mutations associated with resistance to selective FLT3-ITD inhibitors; inhibits the growth of a broad panel of AML cell lines in xenograft models.Blood Cancer Phase 2 Clinical

In MOLM-13 and to a lesser extent in MV4-11 cells, a dose-dependent disruption of cell cycle with especially pronounced depletion of the S phase after treatment with SEL24-B489, accompanied by PARP cleavage and apoptosis was observed.SEL24-B489 causes a profound inhibition of S6 (S235/236), but has little effect on PI3K/mTOR signaling.SEL24-B489 inhibits STAT5 (Ser726) and reduced expression of MCL1, whereas none of the selective inhibitors altered c-MYC abundance or induced PARP cleavage. Cell Viability AssayCell Line:AZD1208, AC220 and AraC in AML cell lines.Concentration:0-10 μM.Incubation Time:72 h. Result:Decreased viability.

SEL24-B489 (25-100 mg/kg, orally) exhibited activity in AML in vivo models.SEL24-B489 induces apoptosis of DLBCL cell lines in low/sub-micromolar concentrations and exhibits activity in a xenograft model. Animal Model:SCID/beige mice bearing MV-4-11 tumors (FLT3-ITD+).Dosage:50, 75 and 100 mg/kg.Administration:Orally, twice daily.Result:Marked dose – dependent tumor reduction (67%, 74% and 82% tumor growth inhibition (TGI) for 50, 75 and 100 mg/kg daily doses, respectively).

SEL24

JAK/STAT Signaling

Pim

Pim

Cancer

Blood cancer

1616359-00-2

446.143

C15H18Br2N4O2

>98% (HPLC)

In Vitro:?DMSO : 25 mg/mL (56.04 mM)

CC(N1C(C2CCNCC2)=NC3=C([N+]([O-])=O)C(Br)=C(Br)C=C31)C.[H]Cl

5,6-dibromo-4-nitro-2-(piperidin-4-yl)-1-(propan-2-yl)-1H-1,3-benzodiazole

(-20℃)

With Ice Pack

≥ 2 years