LGH447 free base | PIM447 | 1210608-43-7 | 1820565-69-2 | PIM inhibitor

MedKoo Cat#: 407201 | Name: LGH447 free base

Description:

WARNING: This product is for research use only, not for human or veterinary use.

PIM447, also known as LGH447, is a potent Moloney murine leukemia (PIM) 1, 2, and 3 kinase inhibitor. Pan proviral insertion site of Moloney murine leukemia (PIM) 1, 2, and 3 kinase inhibitors have recently begun to be tested in humans to assess whether pan PIM kinase inhibition may provide benefit to cancer patients. PIM447 demonstrates in vivo target modulation (pS6RP), single agent antitumor activity in a KG-1 AML mouse xenograft model, and druglike properties suitable for development. PIM447 advanced into humans in 2012 and is currently being assessed in several phase I trials.

Chemical Structure

LGH447 free base

CAS#1210608-43-7 (free base)

Theoretical Analysis

MedKoo Cat#: 407201

Name: LGH447 free base

CAS#: 1210608-43-7 (free base)

Chemical Formula: C24H23F3N4O

Exact Mass: 440.1824

Molecular Weight: 440.47

Elemental Analysis: C, 65.44; H, 5.26; F, 12.94; N, 12.72; O, 3.63

Price and Availability

Size	Price	Availability
5mg	USD 450.00	2 Weeks
10mg	USD 750.00	2 Weeks
25mg	USD 1,450.00	2 Weeks

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Related CAS #

1210416-52-6 (HCl) 1820565-69-2 (2HCl) 1210608-43-7 (free base)

Synonym

LGH-447; LGH 447; LGH447; PIM447; PIM-447; PIM 447; LGH447 free base

IUPAC/Chemical Name

N-(4-((1R,3S,5S)-3-amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide

InChi Key

VRQXRVAKPDCRCI-ZNMIVQPWSA-N

InChi Code

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

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

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

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.

In vitro activity:

PIM447 significantly decreased the viability, proliferation, and motility of HuH6 and COA67 cells. Apoptosis significantly increased following PIM447 treatment. PIM447 had a significant impact on tumor cell stemness as evidenced by decreased expression of CD133 and reduced ability of HuH6 and COA67 cells to form tumorspheres. Reference: J Pediatr Surg. 2021 Jun;56(6):1157-1164. https://pubmed.ncbi.nlm.nih.gov/33762119/

In vivo activity:

Finally, PIM447 significantly reduced the tumor burden and prevented tumor-associated bone loss in a disseminated murine model of human myeloma. Reference: Clin Cancer Res. 2017 Jan 1;23(1):225-238. https://pubmed.ncbi.nlm.nih.gov/27440267/

	Solvent	mg/mL	mM
Solubility
	DMSO	88.0	199.79
	Ethanol	88.0	199.79

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 440.47 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Wadhwani N, Markert HR, Marayati R, Bownes LV, Quinn CH, Aye JM, Stewart JE, Yoon KJ, Beierle EA. PIM447 inhibits oncogenesis and potentiates cisplatin effects in hepatoblastoma. J Pediatr Surg. 2021 Jun;56(6):1157-1164. doi: 10.1016/j.jpedsurg.2021.02.039. Epub 2021 Feb 24. PMID: 33762119; PMCID: PMC8131223. 2. Leung MS, Chan KK, Dai WJ, Wong CY, Au KY, Wong PY, Wong CC, Lee TK, Ng IO, Kao WJ, Lo RC. Anti-tumour effects of PIM kinase inhibition on progression and chemoresistance of hepatocellular carcinoma. J Pathol. 2020 Sep;252(1):65-76. doi: 10.1002/path.5492. Epub 2020 Jul 31. PMID: 32558942. 3. Paíno T, Garcia-Gomez A, González-Méndez L, San-Segundo L, Hernández-García S, López-Iglesias AA, Algarín EM, Martín-Sánchez M, Corbacho D, Ortiz-de-Solorzano C, Corchete LA, Gutiérrez NC, Maetos MV, Garayoa M, Ocio EM. The Novel Pan-PIM Kinase Inhibitor, PIM447, Displays Dual Antimyeloma and Bone-Protective Effects, and Potently Synergizes with Current Standards of Care. Clin Cancer Res. 2017 Jan 1;23(1):225-238. doi: 10.1158/1078-0432.CCR-16-0230. Epub 2016 Jul 20. PMID: 27440267.

In vitro protocol:

In vivo protocol:

1. Paíno T, Garcia-Gomez A, González-Méndez L, San-Segundo L, Hernández-García S, López-Iglesias AA, Algarín EM, Martín-Sánchez M, Corbacho D, Ortiz-de-Solorzano C, Corchete LA, Gutiérrez NC, Maetos MV, Garayoa M, Ocio EM. The Novel Pan-PIM Kinase Inhibitor, PIM447, Displays Dual Antimyeloma and Bone-Protective Effects, and Potently Synergizes with Current Standards of Care. Clin Cancer Res. 2017 Jan 1;23(1):225-238. doi: 10.1158/1078-0432.CCR-16-0230. Epub 2016 Jul 20. PMID: 27440267.

1: Burger MT, Nishiguchi G, Han W, Lan J, Simmons R, Atallah G, Ding Y, Tamez V, Zhang Y, Mathur M, Muller K, Bellamacina C, Lindvall MK, Zang R, Huh K, Feucht P, Zavorotinskaya T, Dai Y, Basham S, Chan J, Ginn E, Aycinena A, Holash J, Castillo J, Langowski JL, Wang Y, Chen MY, Lambert A, Fritsch C, Kauffmann A, Pfister E, Vanasse KG, Garcia PD. 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. doi: 10.1021/acs.jmedchem.5b01275. Epub 2015 Oct 27. PubMed PMID: 26505898. 2: Paíno T, Garcia-Gomez A, González-Méndez L, San-Segundo L, Hernández-García S, López-Iglesias AA, Algarín EM, Martín-Sánchez M, Corbacho D, Ortiz-de-Solorzano C, Corchete LA, Gutiérrez NC, Maetos MV, Garayoa M, Ocio EM. The Novel Pan-PIM Kinase Inhibitor, PIM447, Displays Dual Antimyeloma and Bone-Protective Effects, and Potently Synergizes with Current Standards of Care. Clin Cancer Res. 2017 Jan 1;23(1):225-238. doi: 10.1158/1078-0432.CCR-16-0230. Epub 2016 Jul 20. PubMed PMID: 27440267.