Atiprimod dimaleate
Atiprimod (Azaspirane) (dimaleate) is a STAT3 inhibitor with antitumor, anti-inflammatory, and anti-angiogenic activities. Atiprimod blocks the signaling pathways of IL-6 and VEGF by inhibiting the phosphorylation of signal transducer and activator of STAT3. Atiprimod blocks the JAK-STAT signaling pathway by inhibiting the phosphorylation of JAK2 and JAK3. Atiprimod also inhibits cell proliferation, induces cell cycle arrest, and induces autophagy and apoptosis. Atiprimod triggers persistent ER stress-mediated apoptosis in breast cancer cells by activating the PERK/eIF2α/ATF4/CHOP axis and inhibiting the nuclear translocation of STAT3/NF-κB. Atiprimod shows great anti-tumor activities in tumor xenograft mouse models. Atiprimod can be used for the study of pituitary adenoma, breast cancer, multiple myeloma and acute myeloid leukemia (AML).
For research use only. We do not sell to patients.
- CAS No.: 183063-72-1
- Formula: C30H52N2O8
- Molecular Weight:568.74
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Biological Activity
Atiprimod (0-7 µM, 24 h) decreases viability of GH3 cells, MDA-MB-231 and MDA-MB-468 breast cancer cellsand in a dose-dependent manner[1][2].
Atiprimod (0-3 µM, 24 h) downregulates STAT-1, STAT-3, STAT-5, pSTAT-1, pSTAT-3, pSTAT-5 and GH expressions in GH3 cells[1].
Atiprimod (1-3 µM, 4 days) reduces colony diameter of GH3 cells in hanging drop assay[1].
Atiprimod (1-3 µM, 24 h) triggers ER stress in GH3, MDA-MB-231 and MDA-MB-468 breast cancer cells, as indicated by CHOP activation, dose-dependent Ca2+ release, upregulation of BiP and CHOP, and phosphorylation of AMPK[1][2].
Atiprimod (1-3 µM, 24 h) induces autophagy, apoptosis and triggers ROS generation in GH3, MDA-MB-231 and MDA-MB-468 cells[1][2].
Atiprimod (2 µM, 24 h) enhances viability loss, inhibits growth, and increases subG1 population in STAT3-overexpressing GH3 cells, and prevents upregulation of Atg5, Beclin-1, BiP, CHOP and LC3 cleavage induced by atiprimod in GH3 cells[1].
Atiprimod (0.5-4 μM) inhibits clonogenic growth of AML cell lines (OCIM2, OCI/AML-3, KG-1, K562, HL-60) [3].
Atiprimod (0.5-4 μM, 2 h) decreases phosphorylation of Stat3, Stat5, and protein levels of Jak2 and phospho-Jak2 in K562 cells without affecting Jak2 gene expression[3].
Atiprimod (1-5 μM, 6-48 h) induces apoptosis of MCL cell lines (SP53, MINO, Grant 519, and Jeko-1) and primary MCL cells in both dose- and time-dependent manners, detected by annexin V-binding and TUNEL assays[4].
Atiprimod (5 μM, 1-2 h) inhibits IL-6-induced phosphorylation of JAK2/STAT3 and Akt, and TNF-α-induced phosphorylation of IκB and NFκB p65, while downregulating Mcl-1 in MM.1S cells[5].
Atiprimod (0.6-2.5 μM, 48 h) inhibits growth of MM.1S and U266 cells adherent to BMSCs, and reduces IL-6 and VEGF secretion in BMSCs (alone or with MM cells)[5].
Atiprimod (1.25-2.5 μM, 6 h) inhibits capillary network formation in HUVECs without cytotoxicity, and reduces VEGF secretion in HUVECs and BMSCs[5].
Atiprimod (0.1-0.8 μM, 72 h) inhibits proliferation of mouse FDCP-EpoR JAK2WT cells (IC50 = 0.69 μM), FDCP-EpoR JAK2V617F cells (IC50 = 0.42 μM), human SET-2 cells (JAK2V617F-positive, IC50 = 0.53 μM) and CMK cells (JAK3-mutant, IC50 = 0.79 μM) in a dose-dependent manner[6].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:GH3, MDA-MB-231 and MDA-MB-468 cells
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Concentration:1, 2, 3 µM
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Incubation Time:24 h
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Result:Reduced the expressions of STAT-1, STAT-3, STAT-5, pSTAT-1, pSTAT-3, pSTAT-5, GH, Bcl-2, Bcl-XL and p62.
Increased the expressions of Atg5, Atg12, Beclin-1, LC-3II, BiP, CHOP, p-PERK, p-AMPK, eIF-2, p70S6K, p53, p-p53, Bax, PUMA and Bim.
Activated caspase-3, -6, -7 and PARP cleavage.
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Cell Line:MCL cell lines (SP53, MINO, Grant 519, and Jeko-1)
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Concentration:1, 2, 4, 5 µM
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Incubation Time:6, 12, 24, 48 h
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Result:Activated caspase-9, caspase-3, and cleaves PARP in MCL cells.
up-regulateD Bax, Bad, and phosphorylated Bcl-2.
Atiprimod (50 mg/kg, i.v., once daily, 6 consecutive days) demonstrates significant in vivo anti-tumor efficacy in OPM1 human multiple myeloma xenograft SCID mouse models[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SP53 or Grant 519 cells (5 × 106 in 50 µL PBS) were subcutaneously inoculated into the right flank of 6- to 8-week-old male CB-17 SCID mice[4]
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Dosage:25 mg/kg
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Administration:i.p. once daily for 6 consecutive days
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Result:Achieved significant tumor growth inhibition in SP53 and Grant 519 MCL xenograft SCID mouse models.
Reduced tumor volume and decreased levels of circulating human β2-microglobulin.
Prolonged survival of tumor-bearing mice.
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Animal Model:OPM1 cells (5 × 106 in 100 µL RPMI-1640 medium) were subcutaneously inoculated into the interscapular area of 6- to 8-week-old male CB-17 SCID mice[5]
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Dosage:50 mg/kg
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Administration:i.v. once daily for 6 consecutive days
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Result:Achieved significant tumor growth inhibition in OPM1 human multiple myeloma xenograft SCID mouse models.
Reduced tumor volume in tumor-bearing mice.
Chemical Information
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CAS No. 183063-72-1
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Molecular Weight 568.74
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Formula C30H52N2O8
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SMILES
CCCC(CC1)(CCC)CCC21CCN(CCCN(CC)CC)C2.O=C(O)/C=C\C(O)=O.O=C(O)/C=C\C(O)=O
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Synonyms
Azaspirane dimaleate; SKF 106615-12 dimaleate; SKF 106615A12 dimaleate
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[1]. Coker-Gurkan A, et al. Atiprimod induce apoptosis in pituitary adenoma: Endoplasmic reticulum stress and autophagy pathways. J Cell Biochem. 2019 Dec;120(12):19749-19763. [Content Brief]
[2]. Coker-Gurkan A, et al Atiprimod triggered apoptotic cell death via acting on PERK/eIF2α/ATF4/CHOP and STAT3/NF-ΚB axis in MDA-MB-231 and MDA-MB-468 breast cancer cells. Mol Biol Rep. 2021 Jun;48(6):5233-5247. [Content Brief]
[3]. Faderl S, et al. Atiprimod blocks phosphorylation of JAK-STAT and inhibits proliferation of acute myeloid leukemia (AML) cells. Leuk Res. 2007 Jan;31(1):91-5. [Content Brief]
[4]. Wang M, et al. Atiprimod inhibits the growth of mantle cell lymphoma in vitro and in vivo and induces apoptosis via activating the mitochondrial pathways. Blood. 2007 Jun 15;109(12):5455-62. [Content Brief]
[5]. Hamasaki M, et al. Azaspirane (N-N-diethyl-8,8-dipropyl-2-azaspiro [4.5] decane-2-propanamine) inhibits human multiple myeloma cell growth in the bone marrow milieu in vitro and in vivo. Blood. 2005 Jun 1;105(11):4470-6. [Content Brief]
[6]. Quintás-Cardama A, et al. Preclinical characterization of atiprimod, a novel JAK2 AND JAK3 inhibitor. Invest New Drugs. 2011 Oct;29(5):818-26. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Atiprimod dimaleate Related Classifications
HY-13559A Related Classifications
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- Atiprimod dimaleate
- 183063-72-1
- Azaspirane dimaleate
- SKF 106615-12 dimaleate
- SKF 106615A12 dimaleate
- STAT
- Apoptosis
- Caspase
- Interleukin Related
- Autophagy
- Reactive Oxygen Species (ROS)
- Atg8/LC3
- p62
- JAK
- pituitary adenoma
- breast cancer
- multiple myeloma
- acute myeloid leukemia (AML)
- STAT3
- apoptosis
- autophagy
- Inhibitor
- inhibitor
- inhibit