PIM447

PIM447 (LGH447) is a potent, orally available, and selective pan-PIM kinase inhibitor, with Ki values of 6, 18, and 9 pM for PIM1, PIM2, and PIM3, respectively. PIM447 displays dual antimyeloma and bone-protective effects. PIM447 induces apoptosis.

Product information

CAS Number: 1210608-43-7

Molecular Weight: 440.46

Formula: C24H23F3N4O

Synonym:

LGH447

Chemical Name: N-{4-[(1R, 3S, 5S)-3-amino-5-methylcyclohexyl]pyridin-3-yl}-6-(2, 6-difluorophenyl)-5-fluoropyridine-2-carboxamide

Smiles: C[C@H]1C[C@H](C[C@@H](N)C1)C1=CC=NC=C1NC(=O)C1=CC=C(F)C(=N1)C1C(F)=CC=CC=1F

InChiKey: VRQXRVAKPDCRCI-ZNMIVQPWSA-N

InChi: InChI=1S/C24H23F3N4O/c1-13-9-14(11-15(28)10-13)16-7-8-29-12-21(16)31-24(32)20-6-5-19(27)23(30-20)22-17(25)3-2-4-18(22)26/h2-8,12-15H,9-11,28H2,1H3,(H,31,32)/t13-,14+,15-/m0/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

PIM447 (0.05-10 μM; 24-72 hours) shows antiproliferative effect on the multiple myeloma (MM) cells. PIM447 (10 μM; 6-24 hours) induces apoptosis. PIM447 (0.1-10 μM; 48 hours) increases the percentage of cells in the G0-G1 phase and decreases the proliferative phases (S and G2–M) of the cell cycle, in the two cell lines (MM1S and OPM-2 cells) at all doses.

In Vivo:

PIM447 (100 mg/kg; p.o.; 5 times for a week) reduces tumor burden.

References:

1. Burger MT, et al. Identification of N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide (PIM447), a Potent and Selective Proviral Insertion Site of Moloney Murine Leukemia (PIM) 1, 2, and 3 Kinase Inhibitor in Clinical Trials for Hematological Malignancies.J Med Chem. 2015 Nov 12;58(21):8373-86.
2. Paíno T et al. The novel pan-PIM kinase inhibitor, PIM447, displays dual anti-myeloma and bone protective effects, and potently synergizes with current standards of care. Clin Cancer Res. 2016 Jul 20.
3. Peters TL et al. Control of translational activation by PIM kinase in activated B-cell diffuse large B-cell lymphoma confers sensitivity to inhibition by PIM447. Oncotarget. 2016 Aug 20

Products are for research use only. Not for human use.