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Purity: ≥98%
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.
| 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].
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| 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].
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| 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. |
| Molecular Formula |
C20H22F3N5O
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| Molecular Weight |
405.42
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| Exact Mass |
405.177
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| CAS # |
1025065-69-3
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| Related CAS # |
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| PubChem CID |
24795070
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| Appearance |
White to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.613
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| LogP |
3.36
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
29
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| Complexity |
529
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
SXLKQFDJPFXMGV-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
N-((1-methylpiperidin-4-yl)methyl)-3-(4-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazin-6-amine.
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| Synonyms |
SGI1776; SGI-1776; SGI 1776.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| 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. View More
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. Solubility in Formulation 4: 30% propylene glycol, 5% Tween 80, 65% D5W:30mg/mL |
| 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01239108 | Withdrawn | Drug: SGI-1776 | Relapsed/Refractory Leukemias | Astex Pharmaceuticals, Inc. | October 2010 | Phase 1 |
| NCT00848601 | Terminated | Drug: SGI-1776 | Prostate Cancer Non-Hodgkins Lymphoma |
Astex Pharmaceuticals, Inc. | February 2009 | Phase 1 |
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