GSK864 | GSK-864 | CAS#1816331-66-4 | IDH1 inhibitor

GSK864
featured

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

MedKoo CAT#: 407369

CAS#: 1816331-66-4

Description: GSK864 is a potent and selective inhibitor of mutant IDH1. GSK864 inhibits IDH1 mutants R132C/R132H/R132G with IC50 values of 9/15/17 nM, respectively, and is moderately selective over wild-type IDH1 and IDH2 mutants/wild-type. Treatment of R132C IDH1 mutant HT-1080 cells for 24 hours with GSK864 results in a dose-dependent reduction of 2-hydroxyglutarate (2-HG), which is not observed with GSK990, a structurally similar compound which is inactive as an IDH1 inhibitor. GSK864 has been shown to be selective in vitro for IDH1 over other classes of proteins (7TMs, ion channels, kinases) and chemoproteomic studies with GSK321, an analog of GSK864, confirm selective binding of IDH1 by this chemical series. GSK864 has a pharmacokinetic profile suitable for in vivo studies.

Chemical Structure

GSK864

CAS# 1816331-66-4

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 407369
Name: GSK864
CAS#: 1816331-66-4
Chemical Formula: C30H31FN6O4
Exact Mass: 558.24
Molecular Weight: 558.614
Elemental Analysis: C, 64.50; H, 5.59; F, 3.40; N, 15.04; O, 11.46

Price and Availability

Size	Price	Availability
5mg	USD 450	2 Weeks
25mg	USD 1450	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: GSK864; GSK-864; GSK 864.

IUPAC/Chemical Name: (S)-1-(4-fluorobenzyl)-N3-(4-methoxy-3,5-dimethylphenyl)-7-methyl-5-(1H-pyrrole-2-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-3,7-dicarboxamide

InChi Key: DUCNNEYLFOQFSW-PMERELPUSA-N

InChi Code: InChI=1S/C30H31FN6O4/c1-17-12-21(13-18(2)25(17)41-4)34-27(38)24-22-15-36(28(39)23-6-5-11-33-23)16-30(3,29(32)40)26(22)37(35-24)14-19-7-9-20(31)10-8-19/h5-13,33H,14-16H2,1-4H3,(H2,32,40)(H,34,38)/t30-/m0/s1

SMILES Code: O=C(C1=NN(CC2=CC=C(F)C=C2)C3=C1CN(C(C4=CC=CN4)=O)C[C@]3(C)C(N)=O)NC5=CC(C)=C(OC)C(C)=C5

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:

Product Data:

Product Data

Instruction:

View handling instruction

Biological target:	GSK864 is an isocitrate dehydrogenase 1 (IDH1) mutant inhibitor; inhibits IDH1 mutants R132C, R132H, and R132G with IC50 values of 8.8, 15.2 and 16.6 nM.
In vitro activity:	Indeed, GSK864 attenuated the proliferation of both fibrosarcoma cells and normal fibroblasts with a similar trend (Figure 5B). Despite their different proliferation rates, GSK864 significantly reduced the proliferation of fibrosarcoma cells and normal fibroblasts at doses of 0.8, 1.6 and 2 μmol, relative to control and at doses of 0.2 and 0.4 μmol (Figure 5B). These findings suggest that GSK864 not only attenuated the proliferation of IDH1 mutant cancer cells, but also fibroblasts such as those found in cancer stroma. Thus, GSK864 attenuation of vascular-endothelial tube formation (Figure 3), reversable by IDH mutant 2HG to which GSK864 inhibits, may represent a novel me-chanism by which GSK864 or other small molecules may be harnessed to target cancer stromal cells. Reference: Am J Cancer Res. 2019 Jan 1;9(1):122-133. https://pubmed.ncbi.nlm.nih.gov/30755816/
In vivo activity:	IDH1 WT or mutant AML patient BM cells were transplanted into sublethally irradiated NSG mice (Supplementary Fig. 4a), and comparable levels of AML engraftment were observed in BM aspirates 3 weeks after transplantation, and prior to treatment with either vehicle or 150 mg/kg GSK864. Following treatment this study observed a decrease in 2HG in IDH1-mutant AML cells of GSK321 treated mice (Supplementary Fig. 3f). After treatment with GSK864, this study observed a significant decrease in the percentage of blast cells (SSClow CD45low/+) and a relative increase in mature lymphoid and granulocytic/monocytic cells (Supplementary Fig. 4c). Reference: Nat Chem Biol. 2015 Nov;11(11):878-86. https://pubmed.ncbi.nlm.nih.gov/26436839/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMF	20.0	35.80
	DMSO	60.0	107.41
	Ethanol	20.0	35.80
	Ethanol:PBS (pH 7.2) (1:1)	0.5	0.90

Preparing Stock Solutions

The following data is based on the product molecular weight 558.61 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. Mao MJ, Leonardi DE. Vascular-endothelial response to IDH1 mutant fibrosarcoma secretome and metabolite: implications on cancer microenvironment. Am J Cancer Res. 2019 Jan 1;9(1):122-133. PMID: 30755816; PMCID: PMC6356916. 2. Okoye-Okafor UC, Bartholdy B, Cartier J, Gao EN, Pietrak B, Rendina AR, Rominger C, Quinn C, Smallwood A, Wiggall KJ, Reif AJ, Schmidt SJ, Qi H, Zhao H, Joberty G, Faelth-Savitski M, Bantscheff M, Drewes G, Duraiswami C, Brady P, Groy A, Narayanagari SR, Antony-Debre I, Mitchell K, Wang HR, Kao YR, Christopeit M, Carvajal L, Barreyro L, Paietta E, Makishima H, Will B, Concha N, Adams ND, Schwartz B, McCabe MT, Maciejewski J, Verma A, Steidl U. New IDH1 mutant inhibitors for treatment of acute myeloid leukemia. Nat Chem Biol. 2015 Nov;11(11):878-86. doi: 10.1038/nchembio.1930. Epub 2015 Oct 5. PMID: 26436839; PMCID: PMC5155016.
In vitro protocol:	1. Mao MJ, Leonardi DE. Vascular-endothelial response to IDH1 mutant fibrosarcoma secretome and metabolite: implications on cancer microenvironment. Am J Cancer Res. 2019 Jan 1;9(1):122-133. PMID: 30755816; PMCID: PMC6356916. 2. Okoye-Okafor UC, Bartholdy B, Cartier J, Gao EN, Pietrak B, Rendina AR, Rominger C, Quinn C, Smallwood A, Wiggall KJ, Reif AJ, Schmidt SJ, Qi H, Zhao H, Joberty G, Faelth-Savitski M, Bantscheff M, Drewes G, Duraiswami C, Brady P, Groy A, Narayanagari SR, Antony-Debre I, Mitchell K, Wang HR, Kao YR, Christopeit M, Carvajal L, Barreyro L, Paietta E, Makishima H, Will B, Concha N, Adams ND, Schwartz B, McCabe MT, Maciejewski J, Verma A, Steidl U. New IDH1 mutant inhibitors for treatment of acute myeloid leukemia. Nat Chem Biol. 2015 Nov;11(11):878-86. doi: 10.1038/nchembio.1930. Epub 2015 Oct 5. PMID: 26436839; PMCID: PMC5155016.
In vivo protocol:	1. Okoye-Okafor UC, Bartholdy B, Cartier J, Gao EN, Pietrak B, Rendina AR, Rominger C, Quinn C, Smallwood A, Wiggall KJ, Reif AJ, Schmidt SJ, Qi H, Zhao H, Joberty G, Faelth-Savitski M, Bantscheff M, Drewes G, Duraiswami C, Brady P, Groy A, Narayanagari SR, Antony-Debre I, Mitchell K, Wang HR, Kao YR, Christopeit M, Carvajal L, Barreyro L, Paietta E, Makishima H, Will B, Concha N, Adams ND, Schwartz B, McCabe MT, Maciejewski J, Verma A, Steidl U. New IDH1 mutant inhibitors for treatment of acute myeloid leukemia. Nat Chem Biol. 2015 Nov;11(11):878-86. doi: 10.1038/nchembio.1930. Epub 2015 Oct 5. PMID: 26436839; PMCID: PMC5155016.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.

Mass

Concentration

Volume

M. Wt* g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

Dilution Calculator

Calculate the dilution required to prepare a stock solution.

Concentration 1

Volume 1

Concentration 2

Volume 2

1. Mao MJ, Leonardi DE. Vascular-endothelial response to IDH1 mutant fibrosarcoma secretome and metabolite: implications on cancer microenvironment. Am J Cancer Res. 2019 Jan 1;9(1):122-133. PMID: 30755816; PMCID: PMC6356916.

2. Barghout SH, Mann MK, Aman A, Yu Y, Alteen MG, Schimmer AD, Schapira M, Arrowsmith CH, Barsyte-Lovejoy D. Combinatorial Anticancer Drug Screen Identifies Off-Target Effects of Epigenetic Chemical Probes. ACS Chem Biol. 2022 Oct 21;17(10):2801-2816. doi: 10.1021/acschembio.2c00451. Epub 2022 Sep 9. PMID: 36084291.

Your view history

GSK864 featured