PIM-447 dihydrochloride

Research use only, not for human use.

A highly potent and selective inhibitor of pan-Pim with IC50s of 6/18/9 pM for Pim/1/2/3 respectively.

A highly potent and selective inhibitor of pan-Pim with IC50s of 6/18/9 pM for Pim/1/2/3 respectively; induces apoptosis by a decrease in phospho-Bad Ser112 and c-Myc levels and the inhibition of mTORC1 pathway; significantly reduces the tumor burden and prevents tumor-associated bone loss in a murine model of human myeloma.Blood Cancer Phase 2 Clinical.

Cell Viability Assay Cell Line:Sensitive MM cell lines: MM1S, MM1R, RPMI-8226, MM144, U266 and NCI-H929 cells .Less sensitive MM cell lines: OPM-2,RPMI-LR5, U266-Dox4 and U266-LR7cells Concentration:0.05-10 μM Incubation Time:24, 48 and 72 hours Result:Was cytotoxic for MM cells (PIM kinases highly expressed). Apoptosis Analysis Cell Line:Sensitive MM cell lines: MM1S, NCI-H929 and RPMI-8226 cells.Less sensitive MM cell lines: OPM-2 and RPMI-LR5 cells Concentration:0.05-10 μM Incubation Time:24, 48 and 72 hours Result:Induced cell apoptosis at higer doses, had no effects at 0.1-1 uM.Western Blot Analysis Cell Line:Sensitive MM cell lines: MM1S, NCI-H929 and RPMI-8226 cells Concentration:0.05-10 μM Incubation Time:24, 48 hours Result:Increased the cleavage of the effector caspases 3 and 7, and the PARP cleavage.Cell Cycle Analysis Cell Line:MM1S, OPM-2 cells Concentration:0.1, 0.5 or 1 μM Incubation Time:48 hours Result:Increased the cleavage of the effector caspases 3 and 7, and the PARP cleavage.

Animal Model:RPMI-8226-luc cells are injected intravenously into 6-week-old female NODSCID-IL-2Rγ-/-(NSG) mice Dosage:100 mg/kg Administration:oral gavage; 100 mg/kg; 5 times/week Result:Was well tolerated, as the body weight of mice did not decrease by more than 10%.Increased bone volume density and trabecular number and reduced trabecular separation relative to vehicle group.

LGH-447 dihydrochloride

JAK/STAT Signaling

Pim

Pim

Cancer

Blood cancer

1820565-69-2

513.3827

C24H25Cl2F3N4O

>98% (HPLC)

DMSO: ≥ 46.7 mg/mL

CC1CC(CC(C1)N)C2=C(C=NC=C2)NC(=O)C3=NC(=C(C=C3)F)C4=C(C=CC=C4F)F.Cl.Cl

2-Pyridinecarboxamide, N-[4-[(1R,3S,5S)-3-amino-5-methylcyclohexyl]-3-pyridinyl]-6-(2,6-difluorophenyl)-5-fluoro-, hydrochloride (1:2)

(-20℃)

With Ice Pack

≥ 2 years