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Chemical Structure| 1210608-43-7 Chemical Structure| 1210608-43-7

Structure of PIM447
CAS No.: 1210608-43-7

Chemical Structure| 1210608-43-7

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PIM-447 is pan-PIM kinase inhibitor, including Moloney Murine Leukemia (PIM)1, 2, and 3 Kinase.

Synonyms: LGH447

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Product Details of PIM447

CAS No. :1210608-43-7
Formula : C24H23F3N4O
M.W : 440.46
SMILES Code : O=C(NC1=C([C@H]2C[C@@H](N)C[C@@H](C)C2)C=CN=C1)C3=NC(C4=C(F)C=CC=C4F)=C(F)C=C3
Synonyms :
LGH447
MDL No. :MFCD30489724

Safety of PIM447

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Related Pathways of PIM447

epigenetics
JAK-STAT

Isoform Comparison

Biological Activity

Description
PIM447 (LGH447) is a strong, orally administered, and specific inhibitor targeting all PIM kinases, exhibiting Ki values of 6, 18, and 9 pM for PIM1, PIM2, and PIM3, respectively. PIM447 offers both anti-myeloma and bone-protection benefits, and it triggers apoptosis[1].[2].

In Vitro:

Cell Line
Concentration Treated Time Description References
COA67 cells 7.5 μM 8 hours PIM447 significantly increased apoptosis in COA67 cells. J Pediatr Surg. 2021 Jun;56(6):1157-1164.
NCI-H929 200 nM 72 hours Evaluate the synergistic effect of PIM447 in combination with pomalidomide and dexamethasone, results showed a significant increase in the percentage of apoptotic cells Cancers (Basel). 2020 Sep 24;12(10):2743.
RPMI-8226 100 nM 72 hours Evaluate the synergistic effect of PIM447 in combination with pomalidomide and dexamethasone, results showed a significant increase in the percentage of apoptotic cells Cancers (Basel). 2020 Sep 24;12(10):2743.
MM.1S 100 nM 72 hours Evaluate the synergistic effect of PIM447 in combination with pomalidomide and dexamethasone, results showed a significant increase in the percentage of apoptotic cells Cancers (Basel). 2020 Sep 24;12(10):2743.
HuH6 cells 7.5 μM 72 hours PIM447 significantly increased apoptosis in HuH6 cells. J Pediatr Surg. 2021 Jun;56(6):1157-1164.
MV4-11 cells 2 μM 48 hours PIM447 remarkably enhanced bortezomib-induced apoptosis Transl Oncol. 2019 Feb;12(2):336-349.
COA67 cells 5 μM 24 hours PIM447 significantly decreased the migration and invasion of COA67 cells. J Pediatr Surg. 2021 Jun;56(6):1157-1164.
HuH6 cells 5 μM 24 hours PIM447 significantly decreased the migration and invasion of HuH6 cells. J Pediatr Surg. 2021 Jun;56(6):1157-1164.
COA67 cells 0–20 μM 72 hours PIM447 significantly decreased the viability and proliferation of COA67 cells. J Pediatr Surg. 2021 Jun;56(6):1157-1164.
HuH6 cells 0–12 μM 72 hours PIM447 significantly decreased the viability and proliferation of HuH6 cells. J Pediatr Surg. 2021 Jun;56(6):1157-1164.
Ba/F3 cells 10 µM, 1 µM, 0.1 µM 96 hours Evaluate the effect of PIM447 on the growth and viability of Ba/F3 cells, showing that PIM447 significantly reduces the growth and viability of cells dependent on JAK/STAT pathway mutations. NPJ Precis Oncol. 2024 Jul 20;8(1):152.
M07e cells 10 µM, 1 µM, 0.1 µM 96 hours Evaluate the effect of PIM447 on the growth and viability of M07e cells, showing that PIM447 significantly reduces the growth and viability of cells dependent on JAK/STAT pathway mutations. NPJ Precis Oncol. 2024 Jul 20;8(1):152.
Jurkat cells 10 µM, 1 µM, 0.1 µM 96 hours Evaluate the effect of PIM447 on the growth and viability of Jurkat cells, showing that PIM447 significantly reduces the growth and viability of cells dependent on JAK/STAT pathway mutations. NPJ Precis Oncol. 2024 Jul 20;8(1):152.
UKE-1 cells 300nM 72 hours To assess the effect of PIM447 on pBAD levels, results showed that PIM447 significantly reduced pBAD levels, indicating its on-target effect. Clin Cancer Res. 2021 Jun 15;27(12):3456-3468.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice JAK2V617F-mutant MPN model Oral gavage 12.5mg/kg Daily for 7 weeks To evaluate the effect of PIM447 in combination with ruxolitinib and LEE011, results showed that the combination therapy significantly reduced spleen and liver size, improved bone marrow fibrosis, and prolonged survival. Clin Cancer Res. 2021 Jun 15;27(12):3456-3468.
CB17-SCID mice Human plasmacytoma model Oral and intraperitoneal injection 50 mg/kg 5 times per week, continuous treatment Evaluate the in vivo antitumor effect of PIM447 in combination with pomalidomide and dexamethasone, results showed significant delay in tumor growth and prolonged survival of treated mice Cancers (Basel). 2020 Sep 24;12(10):2743.

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT02160951 Multiple Myeloma PHASE1 COMPLETED 2025-05-16 Novartis Investigative Site, N... More >>agoya-city, Aichi, 467-8602, Japan|Novartis Investigative Site, Kobe-city, Hyogo, 650-0017, Japan|Novartis Investigative Site, Kyoto-city, Kyoto, 602-8566, Japan|Novartis Investigative Site, Okayama-city, Okayama, 701-1192, Japan Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.27mL

0.45mL

0.23mL

11.35mL

2.27mL

1.14mL

22.70mL

4.54mL

2.27mL

References

 

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