SGI-1776 | CAS#1025065-69-3 | PIM inhibitor

SGI-1776
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 205710

CAS#: 1025065-69-3

Description: 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.

Chemical Structure

SGI-1776

CAS# 1025065-69-3

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 205710
Name: SGI-1776
CAS#: 1025065-69-3
Chemical Formula: C20H22F3N5O
Exact Mass: 405.18
Molecular Weight: 405.420
Elemental Analysis: C, 59.25; H, 5.47; F, 14.06; N, 17.27; O, 3.95

Price and Availability

Size	Price	Availability
10mg	USD 150	Ready to ship
25mg	USD 250	Ready to ship
50mg	USD 450	Ready to ship
100mg	USD 750	Ready to ship
200mg	USD 1250	Ready to ship
500mg	USD 2650	2 Weeks
1g	USD 4250	2 Weeks
2g	USD 6750	2 Weeks
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: SGI1776; SGI-1776; SGI 1776.

IUPAC/Chemical Name: N-((1-methylpiperidin-4-yl)methyl)-3-(4-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazin-6-amine.

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)

SMILES Code: FC(F)(F)OC1=CC=C(C2=CN=C3C=CC(NCC4CCN(C)CC4)=NN32)C=C1

Appearance: white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: SGI-1776: results from the pediatric preclinical testing program. Researchers from Children's Hospital of Philadelphia recently reported that SGI-1776 exhibited cytotoxic activity in vitro with a median relative IC(50) of 3.1 ÂµM. SGI-1776 induced significant differences in EFS distribution in vivo in 9 of 31 solid tumor xenografts and in 1 of 8 of the evaluable ALL xenografts. SGI-1776 induced tumor growth inhibition meeting criteria for intermediate EFS T/C activity in 1 of 39 evaluable models. In contrast, SGI-1776 induced complete responses of subcutaneous MV4;11 (B myeloid leukemia). (source: Pediatr Blood Cancer. 2011 Nov 2. doi: 10.1002/pbc.23364. [Epub ahead of print] ) Mechanisms of cytotoxicity: SGI-1776 in acute myeloid leukemia. Chen et al recently report that treatment of AML cells with SGI-1776 resulted in a concentration-dependent induction of apoptosis and we investigated its effect on Pim kinase functions. Phosphorylation of traditional Pim kinase targets, c-Myc(Ser62) and 4E-BP1 (Thr36/Thr47), were both decreased in actively cycling AML cell lines MV-4-11, MOLM-13 and OCI-AML-3. Levels of antiapoptotic proteins Bcl-2, Bcl-x(L), XIAP, and proapoptotic Bak and Bax were unchanged; however, a significant reduction in Mcl-1 was observed. This was correlated with inhibition of global RNA and protein synthesis and MCL-1 transcript decline after SGI-1776 treatment. These data suggest that SGI-1776 mechanism in AML involves Mcl-1 protein reduction. Consistent with cell line data, xenograft model studies with mice bearing MV-4-11 tumors showed efficacy with SGI-1776 . Importantly, SGI-1776 was also cytotoxic in AML primary cells, irrespective of FLT3 mutation status and resulted in Mcl-1 protein decline. (source: Blood. 2011 Jul 21;118(3):693-702. Epub 2011 May 31 .)

Product Data:

Product Data

Certificate of Analysis:

View CoA: current batch, Lot#BBC40612

QC Data:

View QC data: current batch, Lot#BBC40612

Safety Data Sheet (SDS):

View Safety Data Sheet (SDS)

Instruction:

View handling instruction

Biological target:	SGI-1776 is an inhibitor of Pim kinases, with IC50s of 7 nM, 363 nM, and 69 nM for Pim-1, -2 and -3, respectively.
In vitro activity:	SGI-1776 effective inhibits proliferation, colony formation, and migration, and promotes apoptosis in BCPAP and TPC-1 cells by SGI-1776. SGI-1776 exhibited a significant dose-dependent increase in apoptotic death in TPC-1 and BCPAP cells. There was a marked decrease in migration rates for both PTC cell lines after treatment with 2.5 μM or 5 μM SGI-1776 at 24, 48, or 72 h, with a more pronounced inhibitory effect on BRAF-positive BCPAP cells compared to RET/PTC-positive TPC-1 cells. Reference: Mol Cell Endocrinol. 2021 Mar 1;523:111144. https://pubmed.ncbi.nlm.nih.gov/33383107/
In vivo activity:	Pim kinase inhibitors, such as SGI-1776, may be a new strategy for acute myeloid leukemia treatment. SGI-1776 demonstrated potent and sustained antitumor activity in mice bearing MV-4-11 tumors. On day 22, most mice in the 75 mg/kg (8 of 9) and all mice in the 200 mg/kg group experienced complete tumor regression, with only minor regrowth in a few mice. Intermittent treatment schedules (2 oral doses/week) at 100 or 200 mg/kg also achieved potent efficacy. Reference: Blood. 2011 Jul 21; 118(3): 693–702. https://pubmed.ncbi.nlm.nih.gov/21628411/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMSO	103.0	254.06
	Ethanol	81.0	199.79

Preparing Stock Solutions

The following data is based on the product molecular weight 405.42 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:	1. Wen QL, Yi HQ, Yang K, Yin CT, Yin WJ, Xiang FY, Bao M, Shuai J, Song YW, Ge MH, Zhu X. Role of oncogene PIM-1 in the development and progression of papillary thyroid carcinoma: Involvement of oxidative stress. Mol Cell Endocrinol. 2021 Mar 1;523:111144. doi: 10.1016/j.mce.2020.111144. Epub 2020 Dec 28. PMID: 33383107. 2. Hou X, Yu Y, Feng J, Wang J, Zheng C, Ling Z, Ge M, Zhu X. Biochemical changes of salivary gland adenoid cystic carcinoma cells induced by SGI-1776. Exp Cell Res. 2017 Mar 15;352(2):403-411. doi: 10.1016/j.yexcr.2017.02.029. Epub 2017 Feb 20. PMID: 28228352. 3. Takeuchi H, Miyamoto T, Fuseya C, Asaka R, Ida K, Ono M, Tanaka Y, Shinagawa M, Ando H, Asaka S, Shiozawa T. PIM1 is a Poor Prognostic Factor for and Potential Therapeutic Target in Serous Carcinoma of the Endometrium. Int J Gynecol Pathol. 2023 May 1;42(3):282-292. doi: 10.1097/PGP.0000000000000882. Epub 2022 Apr 12. PMID: 35443252. 4. Chen LS, Redkar S, Taverna P, Cortes JE, Gandhi V. Mechanisms of cytotoxicity to Pim kinase inhibitor, SGI-1776, in acute myeloid leukemia. Blood. 2011 Jul 21;118(3):693-702. doi: 10.1182/blood-2010-12-323022. Epub 2011 May 31. PMID: 21628411; PMCID: PMC3142906.
In vitro protocol:	1. Wen QL, Yi HQ, Yang K, Yin CT, Yin WJ, Xiang FY, Bao M, Shuai J, Song YW, Ge MH, Zhu X. Role of oncogene PIM-1 in the development and progression of papillary thyroid carcinoma: Involvement of oxidative stress. Mol Cell Endocrinol. 2021 Mar 1;523:111144. doi: 10.1016/j.mce.2020.111144. Epub 2020 Dec 28. PMID: 33383107. 2. Hou X, Yu Y, Feng J, Wang J, Zheng C, Ling Z, Ge M, Zhu X. Biochemical changes of salivary gland adenoid cystic carcinoma cells induced by SGI-1776. Exp Cell Res. 2017 Mar 15;352(2):403-411. doi: 10.1016/j.yexcr.2017.02.029. Epub 2017 Feb 20. PMID: 28228352.
In vivo protocol:	1. Takeuchi H, Miyamoto T, Fuseya C, Asaka R, Ida K, Ono M, Tanaka Y, Shinagawa M, Ando H, Asaka S, Shiozawa T. PIM1 is a Poor Prognostic Factor for and Potential Therapeutic Target in Serous Carcinoma of the Endometrium. Int J Gynecol Pathol. 2023 May 1;42(3):282-292. doi: 10.1097/PGP.0000000000000882. Epub 2022 Apr 12. PMID: 35443252. 2. Chen LS, Redkar S, Taverna P, Cortes JE, Gandhi V. Mechanisms of cytotoxicity to Pim kinase inhibitor, SGI-1776, in acute myeloid leukemia. Blood. 2011 Jul 21;118(3):693-702. doi: 10.1182/blood-2010-12-323022. Epub 2011 May 31. PMID: 21628411; PMCID: PMC3142906.

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1: Siu A, Virtanen C, Jongstra J. PIM kinase isoform specific regulation of MIG6 expression and EGFR signaling in prostate cancer cells. Oncotarget. 2011 Dec 22. [Epub ahead of print] PubMed PMID: 22193779.

2: Batra V, Maris JM, Kang MH, Reynolds CP, Houghton PJ, Alexander D, Kolb EA, Gorlick R, Keir ST, Carol H, Lock R, Billups CA, Smith MA. Initial testing (stage 1) of SGI-1776, a PIM1 kinase inhibitor, by the pediatric preclinical testing program. Pediatr Blood Cancer. 2011 Nov 2. doi: 10.1002/pbc.23364. [Epub ahead of print] PubMed PMID: 22052829.

3: Mahalingam D, Espitia CM, Medina EC, Esquivel JA 2nd, Kelly KR, Bearss D, Choy G, Taverna P, Carew JS, Giles FJ, Nawrocki ST. Targeting PIM kinase enhances the activity of sunitinib in renal cell carcinoma. Br J Cancer. 2011 Nov 8;105(10):1563-73. doi: 10.1038/bjc.2011.426. Epub 2011 Oct 20. PubMed PMID: 22015557; PubMed Central PMCID: PMC3242528.

4: Chen LS, Redkar S, Taverna P, Cortes JE, Gandhi V. Mechanisms of cytotoxicity to Pim kinase inhibitor, SGI-1776, in acute myeloid leukemia. Blood. 2011 Jul 21;118(3):693-702. Epub 2011 May 31. PubMed PMID: 21628411; PubMed Central PMCID: PMC3142906.

5: Chang M, Kanwar N, Feng E, Siu A, Liu X, Ma D, Jongstra J. PIM kinase inhibitors downregulate STAT3(Tyr705) phosphorylation. Mol Cancer Ther. 2010 Sep;9(9):2478-87. Epub 2010 Jul 28. PubMed PMID: 20667852.

6: Mumenthaler SM, Ng PY, Hodge A, Bearss D, Berk G, Kanekal S, Redkar S, Taverna P, Agus DB, Jain A. Pharmacologic inhibition of Pim kinases alters prostate cancer cell growth and resensitizes chemoresistant cells to taxanes. Mol Cancer Ther. 2009 Oct;8(10):2882-93. PubMed PMID: 19825806; PubMed Central PMCID: PMC2808126.

7: Chen LS, Redkar S, Bearss D, Wierda WG, Gandhi V. Pim kinase inhibitor, SGI-1776, induces apoptosis in chronic lymphocytic leukemia cells. Blood. 2009 Nov 5;114(19):4150-7. Epub 2009 Sep 4. PubMed PMID: 19734450; PubMed Central PMCID: PMC2774551.

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