SMI-4a

Catalog No.S8005 Batch:S800503

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Technical Data

Formula

C11H6F3NO2S
Molecular Weight 273.23 CAS No. 438190-29-5
Solubility (25°C)* In vitro DMSO 55 mg/mL (201.29 mM)
Ethanol 23 mg/mL (84.17 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O

Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.

 2.500mg/ml (9.15mM) Taking the 1 mL working solution as an example, add 50 μL of 50 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description SMI-4a (TCS PIM-1 4a) is a potent inhibitor of Pim1 with IC50 of 17 nM, modestly potent to Pim-2, and does not significantly inhibit any other serine/threonine- or tyrosine-kinases.
Targets
Pim1 [1]
(Cell-free assay)
17 nM
In vitro SMI-4a is an ATP competitive inhibitor of Pim1 with IC50 of 17 nM. This compound shows high selectivity for Pim1 against a panel of kinases. It inhibits the in vitro phosphorylation by Pim-1 of the known substrate, the translational repressor 4E-BP1. This chemical (5μM) inhibits pancreatic and leukemic cells growth. It reduces phosphorylation of the Pim target Bad in prostate and hematopoietic cells. This compound causes cell cycle arrest and reverses the antiapoptotic activity of Pim-1. It increases the amount of p27Kip1 in the nucleus. Its treatment of pre-T-LBL inhibits the mTOR pathway. This compound reduces MYC protein expression in pre-T-LBL. Its treatment induces up-regulation of MAPK pathway.
In vivo SMI-4a (60 mg/Kg) treatment twice daily significantly reduce tumor size and is well tolerated. Tumors harvested 1 hour after the final oral gavage of this compound demonstrates decreased phosphorylation of p70 S6K compared with tumors from mice treated with vehicle, whereas in comparison total p70 S6K expression isunchanged.
Features SMI-4a (5μM) synergizes with rapamycin (5 nM) to cause significant growth inhibition of leukemic cells.

Protocol (from reference)

Animal Study:[2]
  • Animal Models

    Nu/nu nude mice injected with pre-T-LBL cells

  • Dosages

    60 mg/Kg

  • Administration

    p.o.

References

  • http://www.ncbi.nlm.nih.gov/pubmed/?term=19509254
  • http://www.ncbi.nlm.nih.gov/pubmed/?term=19965690

Customer Product Validation

<p>Loss of proliferation in ATL-derived cell lines by the Pim-kinase inhibitors, Smi-4a (C). Cell counts were repeated at least twice. Results represent the percentage of cells alive after 5 days of Pim inhibitor treatment, compared with 5 days treated with DMSO. For Smi-4a treatment, cells were treated with 0, 10, or 20 μM Smi-4a. Normal PBMCs (n = 2) were used as a control. Western blots indicate loss of Pim1 targets, p-4EBP1 (Thr37/46), p-p70S6K (Thr389), and loss of pBad (Ser20) (negligible for Smi-4a) after 24 hours with 0, 10, 20, or 40 μM Smi-4a or DMSO control.</p>

, , Blood, 2016, 127:2439-2450.

Selleck's SMI-4a Has Been Cited by 18 Publications

Constitutive activation of Pim1 kinase is a therapeutic target for adult T-cell leukemia [ Blood, May 19, 2016, 2439-2450] PubMed: 26813676
Palbociclib treatment of FLT3-ITD+ AML cells uncovers a kinase-dependent transcriptional regulation of FLT3 and PIM1 by CDK6 [ Blood, June 9, 2016, 2890-2902] PubMed: 27099147
Antiplatelet properties of Pim kinase inhibition are mediated through disruption of thromboxane A2 receptor signaling [ Haematologica, July 1, 2021, 1968-1978] PubMed: 32467143
Role of NuMA1 in breast cancer stem cells with implications for combination therapy of PIM1 and autophagy inhibition in triple negative breast cancer [ Research Square, 2024 Apr 1, rs.3.rs-3953289] PubMed: 38645153
PIM1 inhibitor SMI-4a attenuated concanavalin A-induced acute hepatitis through suppressing inflammatory responses [ Transl Gastroenterol Hepatol, 2024, 9:14] PubMed: 38716217
Targeting macrophagic PIM-1 alleviates osteoarthritis by inhibiting NLRP3 inflammasome activation via suppressing mitochondrial ROS/Cl- efflux signaling pathway [ J Transl Med, 2023, 21(1):452] PubMed: 37422640
Multicellular immune dynamics implicate PIM1 as a potential therapeutic target for uveitis [ Nat Commun, 2022, 13-1:5866] PubMed: 36195600
Pim1 promotes IFN-β production by interacting with IRF3 [ Exp Mol Med, 2022, 54(11):2092-2103] PubMed: 36446848
Antiplatelet properties of Pim kinase inhibition are mediated through disruption of thromboxane A2 receptor signaling [ Haematologica, 2021 Jul 1, 1968-1978] PubMed: 32467143
Anti-platelet Properties of Pim Kinase Inhibition Is Mediated Through Disruption of Thromboxane A2 Receptor Signalling [ Haematologica, 2020, 28;haematol.2019.223529] PubMed: 32467143

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.