GSK547 | CAS# 2226735-55-1 | RIP1 Kinase Inhibitor

MedKoo Cat#: 573172 | Name: GSK547

Description:

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

GSK547 selectively inhibits RIPK1 by targeting an allosteric regulatory site, blocking necroptotic and pro-inflammatory signaling cascades. In preclinical models of colitis and pancreatic cancer, GSK547 reprograms macrophages toward a pro-inflammatory Th1/Th17-supportive phenotype and enhances cytotoxic T cell activation. Despite its immunomodulatory efficacy, GSK547 was discontinued due to poor metabolic stability, with GSK095 emerging as a more viable clinical candidate.

Chemical Structure

GSK547

CAS#2226735-55-1

Theoretical Analysis

MedKoo Cat#: 573172

Name: GSK547

CAS#: 2226735-55-1

Chemical Formula: C20H18F2N6O

Exact Mass: 396.1510

Molecular Weight: 396.40

Elemental Analysis: C, 60.60; H, 4.58; F, 9.59; N, 21.20; O, 4.04

Price and Availability

Size	Price	Availability
10mg	USD 190.00	Ready to ship
25mg	USD 350.00	Ready to ship
50mg	USD 550.00	Ready to ship
100mg	USD 950.00	Ready to ship
200mg	USD 1,650.00	Ready to ship

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

No Data

Synonym

GSK547, GSK-547, GSK 547, RIP1i

IUPAC/Chemical Name

(S)-6-(4-(5-(3,5-difluorophenyl)-4,5-dihydro-1H-pyrazole-1-carbonyl)piperidin-1-yl)pyrimidine-4-carbonitrile

InChi Key

SJVGFKBLUYAEOK-SFHVURJKSA-N

InChi Code

InChI=1S/C20H18F2N6O/c21-15-7-14(8-16(22)9-15)18-1-4-26-28(18)20(29)13-2-5-27(6-3-13)19-10-17(11-23)24-12-25-19/h4,7-10,12-13,18H,1-3,5-6H2/t18-/m0/s1

SMILES Code

N#CC1=NC=NC(N2CCC(C(N3N=CC[C@H]3C4=CC(F)=CC(F)=C4)=O)CC2)=C1

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

>3 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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot# A9T09K17

QC Data

View QC data: current batch, Lot# A9T09K17

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

GSK547 (GSK'547) is a highly selective and potent inhibitor of receptor-interacting serine/threonine protein kinase 1 (RIPK1) that inhibits macrophage-mediated adaptive immune tolerance in pancreatic cancer.

In vitro activity:

It was postulated that RIP1 signaling governs macrophage differentiation. Consistent with the in vivo data in PDA, RIP1i treatment in vitro directed the programing of bone marrow-derived macrophages (BMDM) towards an immunogenic phenotype, upregulating MHCII, TNFα, and IFNγ, while concomitantly reducing CD206, IL-10 and TGF-β expression (Figure 5A). RIP1i induction of M1like programming in BMDM was confirmed using qPCR (Figure S4A). Moreover, RIP1i upregulated STAT1 signaling in BMDM, which is associated with M1-programming, but reduced STAT3, STAT5, and STAT6 signaling, which are linked to M2-like macrophage differentiation (Figure S4B–D). BMDM generated from RIP1 KD/KI mice similarly exhibited increased M1 polarization and upregulated STAT1 signaling (Figure S4E). Further, RIP1i-treated macrophages displayed enhanced ability to capture antigen (Figure S4F). Reference: Cancer Cell. 2018 Nov 12; 34(5): 757–774.e7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836726/

In vivo activity:

Since it was observed that RIP1i did not directly activate T cells (Figure S3C, D) but TAMs expressed high RIP1 (Figure S1F), it was postulated that RIP1 signaling promotes the expansion and tolerogenic programming of macrophages in PDA, which can secondarily corrupt adaptive tumor immunity. It was found that RIP1i-treatment resulted in a ~40% reduction in TAMs infiltrating orthotopic KPC tumors (Figure 4A, B). Moreover, RIP1i reprogrammed TAMs towards an immunogenic M1-like phenotype, including upregulation of MHC-II, CD86, CD80, TNFα, and IFNγ with a concomitant reduction in CD206, IL-10, and TGF-β (Figure 4C–H). Arg1 expression was also reduced in RIP1i tumors (Figure 4I). TAMs infiltrating PDA tumors in RIP1 KD/KI mice similarly exhibited M1-like programming (Figure 4J). Further, in the liver metastases model, RIP1i treatment also led to higher macrophage expression of MHCII and TNFα, and reduced expression of CD206 and IL-10 (Figure 4K). Reference: Cancer Cell. 2018 Nov 12; 34(5): 757–774.e7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836726/

	Solvent	mg/mL	mM
Solubility
	DMSO	65.0	163.98

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 396.40 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. Wang W, Marinis JM, Beal AM, Savadkar S, Wu Y, Khan M, Taunk PS, Wu N, Su W, Wu J, Ahsan A, Kurz E, Chen T, Yaboh I, Li F, Gutierrez J, Diskin B, Hundeyin M, Reilly M, Lich JD, Harris PA, Mahajan MK, Thorpe JH, Nassau P, Mosley JE, Leinwand J, Kochen Rossi JA, Mishra A, Aykut B, Glacken M, Ochi A, Verma N, Kim JI, Vasudevaraja V, Adeegbe D, Almonte C, Bagdatlioglu E, Cohen DJ, Wong KK, Bertin J, Miller G. RIP1 Kinase Drives Macrophage-Mediated Adaptive Immune Tolerance in Pancreatic Cancer. Cancer Cell. 2018 Nov 12;34(5):757-774.e7. doi: 10.1016/j.ccell.2018.10.006. Erratum in: Cancer Cell. 2020 Oct 12;38(4):585-590. PMID: 30423296; PMCID: PMC6836726.

In vitro protocol:

In vivo protocol:

Zhang Y, Li H, Huang Y, Chen H, Rao H, Yang G, Wan Q, Peng Z, Bertin J, Geddes B, Reilly M, Tran JL, Wang M. Stage-Dependent Impact of RIPK1 Inhibition on Atherogenesis: Dual Effects on Inflammation and Foam Cell Dynamics. Front Cardiovasc Med. 2021 Oct 25;8:715337. doi: 10.3389/fcvm.2021.715337. PMID: 34760938; PMCID: PMC8572953.