SMI-4a

Catalog No.S8005 Batch:S800502

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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 32 mg/mL (117.11 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.
* <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
(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 (55M) inhibits pancreatic and leukaemic cell growth. It reduces phosphorylation of the Pim target Bad in prostate and haematopoietic 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 reduces tumour size and is well tolerated. Tumours harvested 1 hour after the final oral gavage of this compound demonstrate decreased phosphorylation of p70 S6K compared with tumours from mice treated with vehicle, whereas in comparison total p70 S6K expression is unchanged.
Features SMI-4a (55M) synergises with rapamycin (5 nM) to cause significant growth inhibition of leukaemic 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.

Sellecks SMI-4a Has Been Cited by 12 Publications

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
Anti-platelet Properties of Pim Kinase Inhibition Is Mediated Through Disruption of Thromboxane A2 Receptor Signalling [ Haematologica, 2020, 28;haematol.2019.223529] PubMed: 32467143
PIM1 inhibition attenuated endotoxin-induced acute lung injury through modulating ELK3/ICAM1 axis on pulmonary microvascular endothelial cells [ Inflamm Res, 2020, 10.1007/s00011-020-01420-3] PubMed: 33185705
Pim-1 as a Therapeutic Target in Lupus Nephritis. [ Arthritis Rheumatol, 2019, 71(8):1308-1318] PubMed: 30791224
PIM1 inhibitor SMI-4a attenuated lipopolysaccharide-induced acute lung injury through suppressing macrophage inflammatory responses via modulating p65 phosphorylation. [ Int Immunopharmacol, 2019, 73:568-574] PubMed: 31203114
The role of dorsal root ganglia PIM1 in peripheral nerve injury-induced neuropathic pain. [ Neurosci Lett, 2019, 709:134375] PubMed: 31349016
Pim1 promotes cell proliferation and regulates glycolysis via interaction with MYC in ovarian cancer [ Onco Targets Ther, 2018, 11:6647-6656] PubMed: 30349298

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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.