GSK321
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MedKoo CAT#: 407271

CAS#: 1816331-63-1

Description: GSK321 is a potent and selective IDH1 mutant inhibitor. GSK321 potently inhibited intracellular 2-HG production in HT-1080 cells, with a half-maximal effective concentration (EC50) of 85 nM by LC/MS/MS analysis. The inhibition of mutant IDH1 by GSK321 overcomes the pathognomonic differentiation block of AML cells and induces myeloid differentiation of IDH1 mutant cells at the level of leukemic blasts and more stem-like cells.


Chemical Structure

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GSK321
CAS# 1816331-63-1

Theoretical Analysis

MedKoo Cat#: 407271
Name: GSK321
CAS#: 1816331-63-1
Chemical Formula: C28H28FN5O3
Exact Mass: 501.22
Molecular Weight: 501.562
Elemental Analysis: C, 67.05; H, 5.63; F, 3.79; N, 13.96; O, 9.57

Price and Availability

Size Price Availability Quantity
5mg USD 150 Ready to ship
10mg USD 250 Ready to ship
25mg USD 450 Ready to ship
50mg USD 750 Ready to ship
100mg USD 1250 Ready to ship
200mg USD 1950 Ready to ship
500mg USD 4250 Ready to ship
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Synonym: GSK321; GSK 321; GSK-321.

IUPAC/Chemical Name: (R)-1-(4-Fluorobenzyl)-N-(3-((S)-1-hydroxyethyl)phenyl)-7-methyl-5-(1H-pyrrole-2-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-3-carboxamide

InChi Key: IVFDDVKCCBDPQZ-MSOLQXFVSA-N

InChi Code: InChI=1S/C28H28FN5O3/c1-17-14-33(28(37)24-7-4-12-30-24)16-23-25(27(36)31-22-6-3-5-20(13-22)18(2)35)32-34(26(17)23)15-19-8-10-21(29)11-9-19/h3-13,17-18,30,35H,14-16H2,1-2H3,(H,31,36)/t17-,18+/m1/s1

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

Biological target: GSK321 is a potent and selective IDH1 mutant inhibitor.
In vitro activity: Mechanistic cellular activity of GSK321 and GSK990 was evaluated in HT-1080 fibrosarcoma cells, which harbor an R132C IDH1 mutation and have markedly elevated levels of 2-hydroxyglutarate (2-HG). After 24 h of treatment with the compounds, GSK321 potently inhibited intracellular 2-HG production in HT-1080 cells, with a half-maximal effective concentration (EC50) of 85 nM by LC/MS/MS analysis (Fig. 1b). Reference: Nat Chem Biol. 2015 Nov;11(11):878-86. https://pubmed.ncbi.nlm.nih.gov/26436839/
In vivo activity: TBD

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
Soluble in DMSO, not in water 0.0 100.00

Preparing Stock Solutions

The following data is based on the product molecular weight 501.56 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: 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.
In vitro 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.
In vivo protocol: TBD

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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. PubMed PMID: 26436839.

Vaziri-Gohar A, Cassel J, Mohammed FS, Zarei M, Hue JJ, Hajihassani O, Graor HJ, Srikanth YVV, Karim SA, Abbas A, Prendergast E, Chen V, Katayama ES, Dukleska K, Khokhar I, Andren A, Zhang L, Wu C, Erokwu B, Flask CA, Zarei M, Wang R, Rothermel LD, Romani AMP, Bowers J, Getts R, Tatsuoka C, Morton JP, Bederman I, Brunengraber H, Lyssiotis CA, Salvino JM, Brody JR, Winter JM. Limited nutrient availability in the tumor microenvironment renders pancreatic tumors sensitive to allosteric IDH1 inhibitors. Nat Cancer. 2022 Jun 9. doi: 10.1038/s43018-022-00393-y. Epub ahead of print. PMID: 35681100.