SGI-1776 is a novel, potent and ATP-competitive pan-inhibitor of the serine/threonine family of Pim kinase (an enzyme regulating cell survival) with potential antitumor activity. It inhibits Pim with an IC50 of 7 nM in a cell-free assay, and is 50- and 10-fold more selective for Pim2 and Pim3. Through extensive biomedical characterization, SGI-1776 exhibits specificity to the three isoforms of the Pim family, including Pim-1, Pim-2, and Pim-3. SGI-1776 was in phase I clinical trials for the treatment of refractory prostate cancer and non-Hodgkin's lymphoma. However, the study was terminated in November 2010.

Physicochemical Properties

Molecular Formula	C20H22F3N5O
Molecular Weight	405.42
Exact Mass	405.177
CAS #	1025065-69-3
Related CAS #	1025065-69-3
PubChem CID	24795070
Appearance	White to yellow solid powder
Density	1.4±0.1 g/cm3
Index of Refraction	1.613
LogP	3.36
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	5
Heavy Atom Count	29
Complexity	529
Defined Atom Stereocenter Count	0
InChi Key	SXLKQFDJPFXMGV-UHFFFAOYSA-N
InChi Code	InChI=1S/C20H22F3N5O/c1-27-10-8-14(9-11-27)12-24-18-6-7-19-25-13-17(28(19)26-18)15-2-4-16(5-3-15)29-20(21,22)23/h2-7,13-14H,8-12H2,1H3,(H,24,26)
Chemical Name	N-((1-methylpiperidin-4-yl)methyl)-3-(4-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazin-6-amine.
Synonyms	SGI1776; SGI-1776; SGI 1776.
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	In SACC cells, Pim-1 kinase activity and Pim-1 protein expression are inhibited by SGI-1776 free base (2.5, 5 μM). In SACC-83 and SACC-LM cells, SGI-1776 free base (2.5, 5 μM) triggers cell cycle arrest and decreases cell growth [1]. SACC-83 and SACC-LM cells' ability to migrate and invade is inhibited by SGI-1776 free base (5 μM) [1]. Caspase-3 is activated by SGI-1776 free base (0, 2.5, or 5 μM), which causes apoptosis [1]. Adipocyte count is unaffected by the inhibition of TG production and lipid accumulation by SGI-1776 free base (5 µM) [2]. Adipogenesis is inhibited by SGI-1776 free base (5 µM), particularly in the early phases of differentiation. SGI-1776 free base (5 µM) downregulates FAS, leptin, and RANTES during adipocyte development and decreases the expression of C/EBP-α and PPAR-γ as well as the phosphorylation level of STAT-3. Adipocytes express distinct proteins and/or mRNAs [2]. With an IC50 of (5.2±0.6) µM, the free base of SGI-1776 exhibited notable dose-dependent action on HO-8910 cells. In vitro, SGI-1776 free base's inhibitory action rose noticeably from 1.25 µM to 20 µM[3]. The HO-8910 cells' migration and invasion are inhibited by SGI-1776 free base in a dose-dependent manner, with the rate of inhibition peaking at 5 μM [3]. In HO-8910 cells, SGI-1776 free base (2.5, 5 and 10 µM) dose-dependently decreases Pim-1 kinase activity. Furthermore, SGI-1776 free base dramatically reduces cell viability, halting cells in the G1 phase and preventing migration and invasion in addition to downregulating Pim-1 expression [3].
ln Vivo	SGI-1776 free base (75, 200 mg/kg, oral) showed dose-dependent, strong antitumor activity in a mouse MV-4-11 xenograft model [4].
Animal Protocol	Dissolved in 5% dextrose; 75, 200 mg/kg; oral administration Female cNOD-SCID mice
References	[1]. Biochemical changes of salivary gland adenoid cystic carcinoma cells induced by SGI-1776. Exp Cell Res. 2017 Mar 15;352(2):403-411. [2]. The novel anti-adipogenic effect and mechanisms of action of SGI-1776, a Pim-specific inhibitor, in 3T3-L1 adipocytes. Int J Mol Med. 2016 Jan;37(1):157-64. [3]. SGI-1776, an imidazo pyridazine compound, inhibits the proliferation of ovarian cancer cells by inactivating Pim-1. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2014 Jul;39(7):649-57. [4]. Mechanisms of cytotoxicity to Pim kinase inhibitor, SGI-1776, in acute myeloid leukemia. Blood, 2011, 118(3), 693-702.
Additional Infomation	N-[(1-methyl-4-piperidinyl)methyl]-3-[3-(trifluoromethoxy)phenyl]-6-imidazo[1,2-b]pyridazinamine is a member of imidazoles. SGI-1776 has been used in trials studying the treatment of Prostate Cancer, Non-Hodgkins Lymphoma, and Relapsed/Refractory Leukemias. PIM Kinase Inhibitor SGI-1776 is a small-molecule pan-PIM protein kinase inhibitor with potential antineoplastic activity. PIM kinase inhibitor SGI-1776 binds to and inhibits the activities of PIM-1, -2 and -3 serine/threonine kinases, which may result in the interruption of the G1/S phase cell cycle transition, the expression of pro-apoptotic Bcl2 proteins and tumor cell apoptosis. PIM kinases play key roles in cell cycle progression and apoptosis inhibition and may be overexpressed in various malignancies.

Solubility Data

Solubility (In Vitro)

DMSO: 81 mg/mL (199.8 mM) Water:<1 mg/mL Ethanol:81 mg/mL (199.8 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.13 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.13 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (5.13 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 30% propylene glycol, 5% Tween 80, 65% D5W:30mg/mL  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.4666 mL	12.3329 mL	24.6658 mL
	5 mM	0.4933 mL	2.4666 mL	4.9332 mL
	10 mM	0.2467 mL	1.2333 mL	2.4666 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.