Atiprimod hydrochloride  (Synonyms: Azaspirane hydrochloride; SKF 106615-12 hydrochloride; SKF 106615)

Atiprimod (Azaspirane) hydrochloride 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)^{[1][2][3][4][5][6]}.

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.

Atiprimod (25 mg/kg, i.p., once daily, 6 consecutive days) demonstrates significant in vivo anti-tumor efficacy in SP53 and Grant 519 MCL xenograft SCID mouse models^[4].
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.

409.52

C₂₂H₄₆Cl₂N₂

130065-61-1

CCN(CCCN1CCC2(CCC(CCC)(CC2)CCC)C1)CC.Cl.Cl

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [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]