PIM447 (LGH447) is a novel pan-piM kinase inhibitor with a Ki value of 6 pM, 18 pM and 9 pM for PIM1, PIM2 and PIM3, respectively. It can also inhibit GSK3β, PKN1 and PKCτ, but the inhibitory effect is small, IC50 in the range of 1-5 μM. PIM447 can induce apoptosis.

 

Brand: BCM

 

In Vitro: By biochemical detection of 68 different protein kinases (including PIM2) and 9 lipid kinases, PIM447 showed high specificity, among which only PIM2 could be significantly inhibited by PIM447, IC50< 0.003μM. PIM447 can also inhibit GSK3β, PKN1 and PKCτ, but the effect is weak, IC50 between 1-5 μM. The IC50 values of other kinases detected were greater than 9 μM. In subsequent cell experiments, PIM447 showed no activity against GSK3β at concentrations up to 20 μM. PIM447 is cytotoxic to myeloma cells, disrupting their cell cycle and inducing a reduction in Bad(Ser112) and c-Myc levels, thereby inducing apoptosis and inhibiting the mTORC1 pathway. PIM447 also inhibits osteoclast formation and reabsorption in vitro, down-regulates key molecules involved in these processes, destroys F-actin rings, and enhances osteoblast activity and mineralization.

 

Boiling Point: 493.7±45.0 °C(Predicted)

 

pKa: 1.35±0.70(Predicted)

 

Solubility: Soluble in DMSO; Soluble in Ethanol. Insoluble in Water.

 

GHS: GHS07

 

Isomeric SMILES: C[C@H]1C[C@H](C[C@H](C1)N)C2=C(C=NC=C2)NC(=O)C3=NC(=C(C=C3)F)C4=C(C=CC=C4F)F  

 

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 

 

Attribute
[Chem Name]	N-[4-[(1R,3S,5S)-3-amino-5-methylcyclohexyl]pyridin-3-yl]-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamide
[Synonym]	PIM447; LGH447
[CAS No.]	1210608-43-7
[Formula]	C24H23F3N4O
[Molecular]	440.46
[Form]	Solid Powder
[Storage]	Sealed in dry. Stored at -20°C.

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