PIM-447 dihydrochloride (Synonyms: LGH447 dihydrochloride)

Name: PIM-447 dihydrochloride
Brand: MedChemExpress
SKU: HY-19322B
Rating: 5.0 (6 reviews)

Cat. No.: HY-19322B Purity: 99.94%: FAQs
Data Sheet SDS COA Handling Instructions

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

For research use only. We do not sell to patients.

PIM-447 dihydrochloride Chemical Structure

CAS No. : 1820565-69-2

Size	Price	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 384	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 384	In-stock	Estimated Time of Arrival: December 31
Solid
1 mg	USD 135	In-stock	Estimated Time of Arrival: December 31
5 mg	USD 340	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 550	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 1800	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 2550	In-stock	Estimated Time of Arrival: December 31
200 mg		Get quote
500 mg		Get quote

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Customer Review

Based on 6 publication(s) in Google Scholar

Other Forms of PIM-447 dihydrochloride:

(1S,3R,5R)-PIM447 dihydrochloride In-stock
PIM447 Get quote
PIM447 hydrochloride Get quote

5 Publications Citing Use of MCE PIM-447 dihydrochloride

: PIM-447 dihydrochloride purchased from MedChemExpress. Usage Cited in: J Pathol. 2020 Sep;252(1):65-76. [Abstract]; The alteration of MAPK/ERK pathway is validated by Western blotting with tumour lysates from the animal model, as illustrated by a downregulation of pERK1/2 in the PIM447 treatment group.

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PIM1 PIM2 PIM3

Biological Activity
Purity & Documentation
References
Customer Review

Description

IC₅₀ & Target

PIM1

PIM2

PIM3

In Vitro

PIM-447?(0.05-10 μM; 24, 48 and 72 hours) has inhibitory effects in MM cells, it against sensitive cell lines with IC₅₀ values ranging from 0.2 to 3.3 μM (MM1S, MM1R, RPMI-8226, MM144, U266 and NCI-H929) and less sensitive cell lines with IC₅₀ values at 48 h >7 μM (OPM-2, RPMI-LR5, U266-Dox4 and U266-LR7)^[1].
PIM-447?(0.1-10 μM; 24, 48 and 72 hours) does not induce important levels of apoptosis, when PIM447 at 5 μM, it substantially increases annexin-V levels (about 30%) in sensitive cell lines(MM1S, NCI-H929 and RPMI-8226). When PIM447 at 10 μM, it induces apoptosis in all the cell lines but to a lesser extent in OPM-2 and RPMI-LR5^[1].
PIM447 promotes the cleavage of initiator caspases, such as caspases 8 and 9, and increases the cleavage of the effector caspases 3 and 7, together with PARP cleavage in MM1S,RPMI-8226 and NCI-H929 cells^[1].
PIM447 (0.1-1 μM) increases the percentage of cells in the G0/G1 phase and decreases the proliferative phases (S and G2/M) of the cell cycle. The effects at low concentrations (0.1-1 μM) were more pronounced in MM1S cells than in OPM-2^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay^[1]

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^[1]

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^[1]

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^[1]

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.

In Vivo

PIM447 (oral gavage; 100 mg/kg; 5 times/week) clearly controlls tumor progression and the serum levels of hIgλ secreted by RPMI-8226-luc cells in mouse model of bone marrow-disseminated human multiple myeloma^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	RPMI-8226-luc cells are injected intravenously into 6-week-old female NODSCID-IL-2Rγ^-/-(NSG) mice^[1]
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.

Clinical Trial

Molecular Weight

513.38

Formula

C₂₄H₂₅Cl₂F₃N₄O

CAS No.

1820565-69-2

Appearance

Solid

Color

White to off-white

SMILES

O=C(C1=NC(C2=C(F)C=CC=C2F)=C(F)C=C1)NC3=C([C@H]4C[C@@H](N)C[C@@H](C)C4)C=CN=C3.Cl.Cl

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

4°C, sealed storage, away from moisture

*In solvent : -80°C, 1 year; -20°C, 6 months (sealed storage, away from moisture)

Solvent & Solubility

In Vitro:

H₂O : 50 mg/mL (97.39 mM; Need ultrasonic)

DMSO : ≥ 46.7 mg/mL (90.97 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	1.9479 mL	9.7394 mL	19.4787 mL
5 mM	0.3896 mL	1.9479 mL	3.8957 mL
10 mM	0.1948 mL	0.9739 mL	1.9479 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months (sealed storage, away from moisture). When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (4.87 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (4.87 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Calculation results:

Working solution concentration: mg/mL

This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only.If necessary, please contact MedChemExpress (MCE).

Purity & Documentation

Purity: 99.94%

Select Batch:

Data Sheet (284 KB) SDS (252 KB)

COA (254 KB) LCMS (94 KB)

Handling Instructions (2659 KB)

References

[1]. 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. [Content Brief]

[2]. 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. [Content Brief]

[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 [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO / H₂O	1 mM	1.9479 mL	9.7394 mL	19.4787 mL	48.6969 mL
	5 mM	0.3896 mL	1.9479 mL	3.8957 mL	9.7394 mL
	10 mM	0.1948 mL	0.9739 mL	1.9479 mL	4.8697 mL
	15 mM	0.1299 mL	0.6493 mL	1.2986 mL	3.2465 mL
	20 mM	0.0974 mL	0.4870 mL	0.9739 mL	2.4348 mL
	25 mM	0.0779 mL	0.3896 mL	0.7791 mL	1.9479 mL
	30 mM	0.0649 mL	0.3246 mL	0.6493 mL	1.6232 mL
	40 mM	0.0487 mL	0.2435 mL	0.4870 mL	1.2174 mL
	50 mM	0.0390 mL	0.1948 mL	0.3896 mL	0.9739 mL
	60 mM	0.0325 mL	0.1623 mL	0.3246 mL	0.8116 mL
	80 mM	0.0243 mL	0.1217 mL	0.2435 mL	0.6087 mL

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

PIM-447 dihydrochloride Related Classifications

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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PIM-447 dihydrochloride (Synonyms: LGH447 dihydrochloride)

Customer Review

Other Forms of PIM-447 dihydrochloride:

PIM-447 dihydrochloride Related Antibodies

5 Publications Citing Use of MCE PIM-447 dihydrochloride

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•Related Screening Libraries:

•Related Small Molecules:

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View All Pim Isoform Specific Products:

Biological Activity

Purity & Documentation

References

Customer Review

PIM-447 dihydrochloride Related Antibodies

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Complete Stock Solution Preparation Table

PIM-447 dihydrochloride Related Classifications

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