GSK872
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MedKoo CAT#: 530960

CAS#: 1346546-69-7

Description: GSK872 is a receptor-interacting protein kinase-3 (RIP3) inhibitor. GSK872 inhibits TNF- and virus-induced necrosis in 3T3-SA fibroblasts. It also inhibits necrosis induced by toll-like receptor 3 (TLR3).

Chemical Structure

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GSK872
CAS# 1346546-69-7
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 530960
Name: GSK872
CAS#: 1346546-69-7
Chemical Formula: C19H17N3O2S2
Exact Mass: 383.08
Molecular Weight: 383.480
Elemental Analysis: C, 59.51; H, 4.47; N, 10.96; O, 8.34; S, 16.72

Price and Availability

Size Price Availability Quantity
5mg USD 90 Ready to ship
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 1350 Ready to ship
500mg USD 2650 Ready to ship
1g USD 4450 Ready to ship
2g USD 6950 2-3 weeks
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Synonym: GSK872; GSK-872; GSK 872

IUPAC/Chemical Name: N-5-benzothiazolyl-6-[(1-methylethyl)sulfonyl]-4-quinolinamine

InChi Key: ZCDBTQNFAPKACC-UHFFFAOYSA-N

InChi Code: InChI=1S/C19H17N3O2S2/c1-12(2)26(23,24)14-4-5-16-15(10-14)17(7-8-20-16)22-13-3-6-19-18(9-13)21-11-25-19/h3-12H,1-2H3,(H,20,22)

SMILES Code: O=S(C1=CC=C2N=CC=C(NC3=CC=C(SC=N4)C4=C3)C2=C1)(C(C)C)=O

Appearance: 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

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:

Biological target: GSK-872 is a RIPK3 inhibitor, which binds RIP3 kinase domain with an IC50 of 1.8 nM, and inhibits kinase activity with an IC50 of 1.3 nM.
In vitro activity: Findings showed that IM and M–M/DC were the major sources of NLRP3 and caspase-1. To further investigate the RIP3–NLRP3 interaction in monocytes/macrophages, a human monocytic cell line THP-1 was used for the in vitro studies. Stimulation of THP-1 cells with LPS and ATP significantly elevated the expressions of p-RIP3 and p-MLKL. GSK872 inhibited RIP3 mediated necroptosis pathway as demonstrated by western bolt analysis (Fig. 4a, b). This inhibition was not complete but significant. Further immunofluorescence experiment showed that GSK872 significantly inhibited the expression of p-RIP3 and p-MLKL in LPS and ATP stimulated THP-1 cells (Fig. 4c). Stimulation of THP-1 cells with both LPS and ATP resulted in upregulation of NLRP3 and caspase-1p20 subunit. Pretreatment with GSK872 resulted in reduced this expression as demonstrated by western blot analysis (Fig. 5a, b). To further confirm the results of western blot, flow cytometry was used to analyze active caspase-1 in THP-1 cells. The results showed that GSK872 significantly reduced the level of active caspase-1 in THP-1 cells (Fig. 5c). The production of IL-1β and IL-18 in the supernatant was also significantly reduced by GSK872 treatment (Fig. 5d). Reference: J Transl Med. 2018 Aug 20;16(1):233. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/30126430/
In vivo activity: MRL/lpr mice have renal disease at an earlier age within a shorter period. These mice were used to demonstrate the therapeutic effect of targeting RIP3 with its specific inhibitor GSK872. 12-week-old MRL/lpr female mice were either treated with GSK872 or with vehicle (saline). The mice were sacrificed at 18 weeks of age. As shown in Figure 3A, the kidney lysates from mice treated with vehicle had elevated p-RIP3 and p-MLKL activities. In contrast, p-RIP3 and p-MLKL were markedly diminished in the kidney of GSK872 treated mice. Activation of caspase-1, a biomarker of NLRP3 inflammasome activation was readily detected in the kidney lysates of mice treated with vehicle (Figure 3B). The activation of caspase-1 was much less in mice treated with GSK872. Kidney lysates of vehicle-treated mice expressed more NLRP3 inflammasome in comparison with those from GSK872 treated mice. These results indicate that treatment with RIP3 inhibitor is effective in inhibiting both NLRP3 inflammasome and necroptosis pathways activation. Reference: J Autoimmun. 2019 Sep;103:102286. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/31133359/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 77.0 200.79

Preparing Stock Solutions

The following data is based on the product molecular weight 383.48 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.

Recalculate based on batch purity %
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:
In vitro protocol: 1. Chen J, Wang S, Fu R, Zhou M, Zhang T, Pan W, Yang N, Huang Y. RIP3 dependent NLRP3 inflammasome activation is implicated in acute lung injury in mice. J Transl Med. 2018 Aug 20;16(1):233. doi: 10.1186/s12967-018-1606-4. PMID: 30126430; PMCID: PMC6102827.
In vivo protocol: 1. Guo C, Fu R, Zhou M, Wang S, Huang Y, Hu H, Zhao J, Gaskin F, Yang N, Fu SM. Pathogenesis of lupus nephritis: RIP3 dependent necroptosis and NLRP3 inflammasome activation. J Autoimmun. 2019 Sep;103:102286. doi: 10.1016/j.jaut.2019.05.014. Epub 2019 May 24. PMID: 31133359; PMCID: PMC6708470. 2. Chen J, Wang S, Fu R, Zhou M, Zhang T, Pan W, Yang N, Huang Y. RIP3 dependent NLRP3 inflammasome activation is implicated in acute lung injury in mice. J Transl Med. 2018 Aug 20;16(1):233. doi: 10.1186/s12967-018-1606-4. PMID: 30126430; PMCID: PMC6102827.

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1: Liao L, Shang L, Li N, Wang S, Wang M, Huang Y, Chen D, Huang J, Xiong K. Mixed lineage kinase domain-like protein induces RGC-5 necroptosis following elevated hydrostatic pressure. Acta Biochim Biophys Sin (Shanghai). 2017 Oct 1;49(10):879-889. doi: 10.1093/abbs/gmx088. PubMed PMID: 28981598.

2: Cekay MJ, Roesler S, Frank T, Knuth AK, Eckhardt I, Fulda S. Smac mimetics and type II interferon synergistically induce necroptosis in various cancer cell lines. Cancer Lett. 2017 Sep 18. pii: S0304-3835(17)30549-9. doi: 10.1016/j.canlet.2017.09.002. [Epub ahead of print] PubMed PMID: 28923396.

3: Lu B, Gong X, Wang ZQ, Ding Y, Wang C, Luo TF, Piao MH, Meng FK, Chi GF, Luo YN, Ge PF. Shikonin induces glioma cell necroptosis in vitro by ROS overproduction and promoting RIP1/RIP3 necrosome formation. Acta Pharmacol Sin. 2017 Aug 17. doi: 10.1038/aps.2017.112. [Epub ahead of print] PubMed PMID: 28816233.

4: Yang XS, Yi TL, Zhang S, Xu ZW, Yu ZQ, Sun HT, Yang C, Tu Y, Cheng SX. Hypoxia-inducible factor-1 alpha is involved in RIP-induced necroptosis caused by in vitro and in vivo ischemic brain injury. Sci Rep. 2017 Jul 19;7(1):5818. doi: 10.1038/s41598-017-06088-0. PubMed PMID: 28724891; PubMed Central PMCID: PMC5517428.

5: Bhatti IA, Abhari BA, Fulda S. Identification of a synergistic combination of Smac mimetic and Bortezomib to trigger cell death in B-cell non-Hodgkin lymphoma cells. Cancer Lett. 2017 Oct 1;405:63-72. doi: 10.1016/j.canlet.2017.07.008. Epub 2017 Jul 14. PubMed PMID: 28716527.

6: Chen S, Lv X, Hu B, Shao Z, Wang B, Ma K, Lin H, Cui M. RIPK1/RIPK3/MLKL-mediated necroptosis contributes to compression-induced rat nucleus pulposus cells death. Apoptosis. 2017 May;22(5):626-638. doi: 10.1007/s10495-017-1358-2. PubMed PMID: 28289909.

7: Arora D, Siddiqui MH, Sharma PK, Shukla Y. Deltamethrin induced RIPK3-mediated caspase-independent non-apoptotic cell death in rat primary hepatocytes. Biochem Biophys Res Commun. 2016 Oct 14;479(2):217-223. doi: 10.1016/j.bbrc.2016.09.042. Epub 2016 Sep 10. PubMed PMID: 27622324.

8: Gerges S, Rohde K, Fulda S. Cotreatment with Smac mimetics and demethylating agents induces both apoptotic and necroptotic cell death pathways in acute lymphoblastic leukemia cells. Cancer Lett. 2016 May 28;375(1):127-132. doi: 10.1016/j.canlet.2016.02.040. Epub 2016 Mar 2. PubMed PMID: 26944210.

9: Das A, McDonald DG, Dixon-Mah YN, Jacqmin DJ, Samant VN, Vandergrift WA 3rd, Lindhorst SM, Cachia D, Varma AK, Vanek KN, Banik NL, Jenrette JM 3rd, Raizer JJ, Giglio P, Patel SJ. RIP1 and RIP3 complex regulates radiation-induced programmed necrosis in glioblastoma. Tumour Biol. 2016 Jun;37(6):7525-34. doi: 10.1007/s13277-015-4621-6. Epub 2015 Dec 18. PubMed PMID: 26684801.

10: Qiu X, Klausen C, Cheng JC, Leung PC. CD40 ligand induces RIP1-dependent, necroptosis-like cell death in low-grade serous but not serous borderline ovarian tumor cells. Cell Death Dis. 2015 Aug 27;6:e1864. doi: 10.1038/cddis.2015.229. PubMed PMID: 26313915; PubMed Central PMCID: PMC4558516.