ORIC-944 is a selective, orally available allosteric inhibitor targeting EED, a subunit of polycomb repressive complex 2 (PRC2). ORIC-944 has a synergistic effect with androgen receptor pathway inhibitors (ARPIs) and can be used to study metastatic prostate cancer.

Physicochemical Properties

Molecular Formula	C26H25FN6O
Molecular Weight	456.51
CAS #	2369769-29-7
Related CAS #	ORIC-944 TFA
Appearance	White to off-white solid powder
SMILES	C1(NCC2=C3C(=CC=C2F)OCC3)=NC=C(C2=CC=C(CN(C)C)C=C2C)C2=NC(C#N)=CN12
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

Targets	polycomb repressive complex 2; PRC2[1]
ln Vivo	ORIC-944 (30, 100, 200 mg/kg; oral; once daily for 50 days) induced significant tumor regression at all dose levels[3]. ORIC-944 (30 mg/kg; oral; once daily for 30 days) has potent single-agent activity against enzalutamide in a prostate cancer xenograft model [3].
Animal Protocol	Animal/Disease Models: KARPAS-422 DLBCL xenograft model[1] Doses: 30, 100, 200 mg/kg Route of Administration: Oral gavage (p.o.) Experimental Results: Had well tolerated at all dose levels assessed compared to tazemetostat at a clinically relevant dose. Animal/Disease Models: 22Rv1 model Doses: 30 mg/kg Route of Administration: Oral gavage (p.o.) Experimental Results: Made average tumor volume ± SEM, with n=8-10/group. Had a significant difference in ORIC-944 treatment group vs vehicle.
References	[1]. ORIC-944, a potent and selective allosteric PRC2 inhibitor with best-in-class properties, demonstrates combination synergy with AR pathway inhibitors in prostate cancer modelsJ. Cancer Research, 2024, 84(6_Supplement): 6586-6586. [2]. ORIC Pharmaceuticals Provides Initial Phase 1b Data for ORIC-944, Operational Highlights for 2023, and Anticipated Upcoming Milestoneshttps://investors.oricpharma.com/news-releases/news-release-details/oric-pharmaceuticals-provides-initial-phase-1b-data-oric-944/.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~219.05 mM; with ultrasonication)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.48 mM)(saturation unknown) in 10% DMSO 40% PEG300 5% Tween-80 45% Saline (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 25.0 mg/mL clear DMSO stock solution and add it to 400 μL PEG300, mix well; then add 50 μL Tween-80 to the above system, mix well; then continue to add 450 μL of normal saline to make up to 1 mL. Preparation of normal saline: Dissolve 0.9 g of sodium chloride in ddH₂O and make up to 100 mL to obtain a clear and transparent normal saline solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.48 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 25.0 mg/mL clear DMSO stock solution and add it to 900 μL corn oil and mix well.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1905 mL	10.9527 mL	21.9053 mL
	5 mM	0.4381 mL	2.1905 mL	4.3811 mL
	10 mM	0.2191 mL	1.0953 mL	2.1905 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.