IDH889 is an orally bioavailable, brain-penetrating, allosteric and mutation-specific inhibitor of isocitrate dehydrogenase (IDH1). IDH889 has high selectivity for IDH1 R132* mutant, with IC50s of 0.02 μM, 0.072 μM and 1.38 μM for IDH1R132H, IDH1R132C and IDH1wt respectively. IDH889 has a potent inhibitory activity against intracellular 2-HG levels, with IC50 of 0.014 μM.

Physicochemical Properties

Molecular Formula	C23H25FN6O2
Molecular Weight	436.482007741928
Exact Mass	436.202
CAS #	1429179-07-6
Related CAS #	(1R)-IDH889;1429179-08-7
PubChem CID	71542286
Appearance	White to off-white solid powder
LogP	4.1
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	6
Heavy Atom Count	32
Complexity	632
Defined Atom Stereocenter Count	2
SMILES	FC1C=CC(=CC=1C)C1C=NC([C@H](C)NC2=NC=CC(=N2)N2C(=O)OC[C@@H]2C(C)C)=NC=1
InChi Key	JDCYIMQAIKEACU-HNAYVOBHSA-N
InChi Code	InChI=1S/C23H25FN6O2/c1-13(2)19-12-32-23(31)30(19)20-7-8-25-22(29-20)28-15(4)21-26-10-17(11-27-21)16-5-6-18(24)14(3)9-16/h5-11,13,15,19H,12H2,1-4H3,(H,25,28,29)/t15-,19+/m0/s1
Chemical Name	(4S)-3-[2-[[(1S)-1-[5-(4-fluoro-3-methylphenyl)pyrimidin-2-yl]ethyl]amino]pyrimidin-4-yl]-4-propan-2-yl-1,3-oxazolidin-2-one
Synonyms	IDH 889; IDH-889; IDH889
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

References

[1]. Optimization of 3-Pyrimidin-4-yl-oxazolidin-2-ones as Allosteric and Mutant Specific Inhibitors of IDH1. ACS Med Chem Lett. 2016 Dec 16;8(2):151-156.

Solubility Data

Solubility (In Vitro)

DMSO : ~200 mg/mL (~458.21 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 5 mg/mL (11.46 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (11.46 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2911 mL	11.4553 mL	22.9106 mL
	5 mM	0.4582 mL	2.2911 mL	4.5821 mL
	10 mM	0.2291 mL	1.1455 mL	2.2911 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.