WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H407271
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.
Hodoodo Cat#: H407271
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
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 |
Solvent | Max Conc. mg/mL | Max Conc. mM | |
---|---|---|---|
Solubility | |||
Soluble in DMSO, not in water | 0.0 | 100.00 |
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.
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 |
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.