SGI-1776 free base

Name: SGI-1776 free base
Brand: MedChemExpress
SKU: HY-13287
Rating: 5.0 (9 reviews)

Cat. No.: HY-13287 Purity: 99.23%: FAQs
Data Sheet SDS COA Handling Instructions

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SGI-1776 free base is an inhibitor of Pim kinases, with IC₅₀s of 7 nM, 363 nM, and 69 nM for Pim-1, -2 and -3, respectively.

For research use only. We do not sell to patients.

SGI-1776 free base Chemical Structure

CAS No. : 1025065-69-3

Size	Price	Stock	Quantity

Free Sample (0.1 - 0.5 mg)		Apply Now
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 131	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 131	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	USD 119	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 224	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 581	In-stock	Estimated Time of Arrival: December 31
100 mg		Get quote
200 mg		Get quote

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Customer Review

Based on 9 publication(s) in Google Scholar

Other Forms of SGI-1776 free base:

SGI-1776 Get quote

8 Publications Citing Use of MCE SGI-1776 free base

: SGI-1776 free base purchased from MedChemExpress. Usage Cited in: Cell Death Dis. 2018 Feb 22;9(3):307. [Abstract]; PIM1 directly phosphorylated Smad2 and Smad3 and that inhibition of PIM1 kinase activity with SGI-1776 significantly reduces the protein levels of p-Smad2 and p-Smad3

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PIM1 PIM2 PIM3

Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

SGI-1776 free base is an inhibitor of Pim kinases, with IC₅₀s of 7 nM, 363 nM, and 69 nM for Pim-1, -2 and -3, respectively.

IC₅₀ & Target

Ki: 7 nM (Pim-1), 363 nM (Pim-2), 69 nM (Pim-3)^[4]

Cellular Effect

Cell Line	Type	Value	Description	References
CHO	IC₅₀	< 1 μM Compound: SGI-1776	Inhibition of human ERG expressed in CHO cells by automated patch clamp method Inhibition of human ERG expressed in CHO cells by automated patch clamp method	[PMID: 25589932]
HL-60	GI₅₀	1.28 μM Compound: SGI-1776	Antiproliferative activity against human HL-60 cells assessed as reduction of cell viability incubated for 72 hrs by trypan blue staining based cell counting analysis Antiproliferative activity against human HL-60 cells assessed as reduction of cell viability incubated for 72 hrs by trypan blue staining based cell counting analysis	[PMID: 34515481]
K562	GI₅₀	2.19 μM Compound: SGI-1776	Antiproliferative activity against human K562 cells assessed as reduction of cell viability incubated for 72 hrs by trypan blue staining based cell counting analysis Antiproliferative activity against human K562 cells assessed as reduction of cell viability incubated for 72 hrs by trypan blue staining based cell counting analysis	[PMID: 34515481]
KMS-11	EC₅₀	5 μM Compound: 1; SGI-1776	Antiproliferative activity against luciferase expressing human KMS11 cells after 72 hrs by Cell-TiterGlo assay Antiproliferative activity against luciferase expressing human KMS11 cells after 72 hrs by Cell-TiterGlo assay	[PMID: 26505898]
LNCaP	IC₅₀	6.85 μM Compound: SGI-1776	Antiproliferative activity against human LNCAP cells after 96 hrs by MTT assay Antiproliferative activity against human LNCAP cells after 96 hrs by MTT assay	[PMID: 26804231]
MOLM-13	GI₅₀	0.13 μM Compound: SGI-1776	Antiproliferative activity against human MOLM13 cells assessed as reduction of cell viability incubated for 72 hrs by trypan blue staining based cell counting analysis Antiproliferative activity against human MOLM13 cells assessed as reduction of cell viability incubated for 72 hrs by trypan blue staining based cell counting analysis	[PMID: 34515481]
NCI-H1299	EC₅₀	200 nM Compound: SGI-1776	Inhibition of PIM1 in human NCI-H1299 cells assessed as reduction in BAD phosphorylation at Ser-112 residue incubated for 4 hrs by ELISA Inhibition of PIM1 in human NCI-H1299 cells assessed as reduction in BAD phosphorylation at Ser-112 residue incubated for 4 hrs by ELISA	[PMID: 30802730]
PC-3	GI₅₀	4.86 μM Compound: SGI-1776	Antiproliferative activity against human PC3 cells after 96 hrs by MTT assay Antiproliferative activity against human PC3 cells after 96 hrs by MTT assay	[PMID: 26979485]
PC-3	IC₅₀	4.86 μM Compound: SGI-1776	Antiproliferative activity against human PC3 cells after 96 hrs by MTT assay Antiproliferative activity against human PC3 cells after 96 hrs by MTT assay	[PMID: 26804231]
WI-38	IC₅₀	1700 nM Compound: SGI-1776	Growth inhibition of human WI38 cells after 48 hrs by CCK8 assay Growth inhibition of human WI38 cells after 48 hrs by CCK8 assay	[PMID: 28523101]

In Vitro

SGI-1776 free base (2.5, 5 μM) inhibits Pim-1 protein expression and Pim-1 kinase activity in SACC cells. SGI-1776 free base (2.5, 5 μM) causes cell cycle arrest and reduces cell proliferation in SACC-83 and SACC-LM cells^[1].
SGI-1776 free base (5 μM) inhibits cell migration and invasiveness in both SACC-83 and SACC-LM cells. SGI-1776 free base (0, 2.5, or 5 μM) induces apoptosis via Caspase-3 activation^[1].
SGI-1776 free base (5 µM) exerts inhibitory effects on both lipid accumulation and TG synthesis without affecting the number of adipocytes^[2].
SGI-1776 free base (5 µM) inhibits adipogenesis particularly at an early phase of differentiation^[2].
SGI-1776 free base (5 µM) decreases the expression of C/EBP-α and PPAR-γ and the phosphorylation levels of STAT-3 during adipocyte differentiation, and downregulates the protein and/or mRNA expression of FAS, leptin and RANTES during adipocyte differentiation^[2].
SGI-1776 free base shows the significant activity against HO-8910 cells in a dose-dependent manner, with IC₅₀ of (5.2±0.6) µM, and the inhibiting effect of SGI-1776 free base is sharply increased from 1.25 µM to 20 µM in vitro^[3].
SGI-1776 free base inhibits the migration and invasion of HO-8910 cells in a dose-dependent manner, and the inhibiting migration and invasion rate of 5 µM^[3].
SGI-1776 free base (2.5, 5 and 10 µM) decreases Pim-1 kinase activity of HO-8910 cells in a dose-dependent manner. Furthermore, the down-regulation of Pim-1 expression by SGI-1776 free base significantly inhibits cell viability, arrests cell in G1 phase, and inhibits the migration and invasion^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

SGI-1776 free base (75, 200 mg/kg, p.o.) shows potent and sustained antitumor activity in a dose dependent manner in MV-4-11 xenografts in mice^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

Molecular Weight

405.42

Formula

C₂₀H₂₂F₃N₅O

CAS No.

1025065-69-3

Appearance

Solid

Color

White to yellow

SMILES

CN1CCC(CC1)CNC2=NN3C(C=C2)=NC=C3C4=CC=CC(OC(F)(F)F)=C4

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Solvent & Solubility

In Vitro:

DMSO : 125 mg/mL (308.32 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent Mass	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

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.08 mg/mL (5.13 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.08 mg/mL (5.13 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.08 mg/mL (5.13 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Purity & Documentation

Purity: 99.23%

Select Batch:

Data Sheet (281 KB) SDS (393 KB)

COA (248 KB) LCMS (122 KB)

Handling Instructions (2659 KB)

References

[1]. Hou X, et al. Biochemical changes of salivary gland adenoid cystic carcinoma cells induced by SGI-1776. Exp Cell Res. 2017 Mar 15;352(2):403-411. [Content Brief]

[2]. Park YK, et al. 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 [Content Brief]

[3]. Xie J, et al. 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 [Content Brief]

[4]. Chen LS, et al. Mechanisms of cytotoxicity to Pim kinase inhibitor, SGI-1776, in acute myeloid leukemia. Blood, 2011, 118(3), 693-702. [Content Brief]

Kinase Assay ^[1]	SACC-83 free base and SACC-LM cells of 0 μM, 2.5 μM and 5 μM groups after SGI-1776 exposure are harvested. 6 samples of SACC cells are diluted in Kinase buffer and pipetted into the wells which is pre-coated with a substrate corresponding to recombinant p21waf1. It contains threonine residues that can be efficiently phosphorylated by Pim-1. After undergoing the procedure, measure absorbance in each well is quantitated by spectrophotometry at dual wavelengths of 450/540 nm. It reflects the relative amount of Pim-1 activity in the 6 groups of SACC cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay ^[3]	Cells are seeded in a 96-well plate at a density of 5 000 cells/well. After incubation for 24 h, different concentrations of SGI-1776 (0.625, 1.25, 2.5, 5, 10, 20, 40 µM) are added to each well and cultured for 48 h. The medium is removed and then incubated with 5 mg/L MTT for 4 h. Next, the supernatant is removed after centrifugation. Finally, 100 µL of DMSO is added and an absorbance at 570 nm wavelength (A570) is measured by enzyme-labeling instrument. Relative cell proliferation inhibition rate (IR)=(1-average A570 of the experimental group/average A570 of the control group)×100%. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[4]	The conditions for animal room environment and photoperiod are 20-25°C, 40%-70% humidity, and 12 hours of light/12 hours of dark cycle. Each mouse is inoculated subcutaneously at the right flank with MV-4-11 tumor cells (5×10⁶). The treatments start when the tumor size reach 80-150 mm³. Mice are randomized to treatment groups based on their tumor sizes; tumor size is measured in 2 dimensions using a caliper, and the volume is expressed in mm³ using the formula: V = 0.5 a × b² where a and b are the long and short diameters of the tumor, respectively. Pretreatment randomization ensures that each group has approximately the same mean tumor size. Mice are treated with vehicle (5% dextrose), SGI-1776 or cytarabine (ara-C). SGI-1776 and ara-C are formulated in 5% dextrose. SGI-1776 is administered by oral gavage (PO) on a daily × 5/week or twice/week schedule; ara-C is administered by intraperitoneal injection 3 times/week for 3 consecutive weeks. Animals are euthanized when their measured tumor size is greater than 3000 mm³ or when they lose ≥ 20% initial body weight; if the body weight loss ≥ 15%, treatment is stopped at first until mice regain body weight. Mice are euthanized when body weight loss is still ≥ 20% even after stopping treatment. T/C value (in %) is an indication of antitumor efficacy, where T and C are the mean tumor volume of the treated and control groups, respectively, on a given day. The differences between the mean tumor sizes for comparing groups is analyzed using the ANOVA test, where P ≤ 0.05 is considered to be statistically significant. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References	[1]. Hou X, et al. Biochemical changes of salivary gland adenoid cystic carcinoma cells induced by SGI-1776. Exp Cell Res. 2017 Mar 15;352(2):403-411. [Content Brief] [2]. Park YK, et al. 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 [Content Brief] [3]. Xie J, et al. 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 [Content Brief] [4]. Chen LS, et al. Mechanisms of cytotoxicity to Pim kinase inhibitor, SGI-1776, in acute myeloid leukemia. Blood, 2011, 118(3), 693-702. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	2.4666 mL	12.3329 mL	24.6658 mL	61.6644 mL
	5 mM	0.4933 mL	2.4666 mL	4.9332 mL	12.3329 mL
	10 mM	0.2467 mL	1.2333 mL	2.4666 mL	6.1664 mL
	15 mM	0.1644 mL	0.8222 mL	1.6444 mL	4.1110 mL
	20 mM	0.1233 mL	0.6166 mL	1.2333 mL	3.0832 mL
	25 mM	0.0987 mL	0.4933 mL	0.9866 mL	2.4666 mL
	30 mM	0.0822 mL	0.4111 mL	0.8222 mL	2.0555 mL
	40 mM	0.0617 mL	0.3083 mL	0.6166 mL	1.5416 mL
	50 mM	0.0493 mL	0.2467 mL	0.4933 mL	1.2333 mL
	60 mM	0.0411 mL	0.2055 mL	0.4111 mL	1.0277 mL
	80 mM	0.0308 mL	0.1542 mL	0.3083 mL	0.7708 mL
	100 mM	0.0247 mL	0.1233 mL	0.2467 mL	0.6166 mL