CC-90005 is a specific and orally bioactive protein kinase C-theta (PKC-theta) inhibitor (antagonist) with IC50 of 8 nM. CC-90005 shows selectivity for PKC-θ over PKC-δ (IC50=4440 nM). CC-90005 can inhibit T cell activation by inhibiting IL-2 expression.

Physicochemical Properties

Molecular Formula	C21H27F2N7O2
Molecular Weight	447.481590509415
Exact Mass	447.219
CAS #	1799574-70-1
PubChem CID	118162109
Appearance	White to off-white solid powder
LogP	3.7
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	8
Heavy Atom Count	32
Complexity	659
Defined Atom Stereocenter Count	2
SMILES	FC(C)(COC1C(=CN=CN=1)CNC1=NC=C(C#N)C(=N1)N[C@@H]1CC[C@@H](C(C)(C)C1)O)F
InChi Key	FMKGJQHNYMWDFJ-CVEARBPZSA-N
InChi Code	InChI=1S/C21H27F2N7O2/c1-20(2)6-15(4-5-16(20)31)29-17-13(7-24)9-26-19(30-17)27-10-14-8-25-12-28-18(14)32-11-21(3,22)23/h8-9,12,15-16,31H,4-6,10-11H2,1-3H3,(H2,26,27,29,30)/t15-,16+/m1/s1
Chemical Name	2-[[4-(2,2-difluoropropoxy)pyrimidin-5-yl]methylamino]-4-[[(1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl]amino]pyrimidine-5-carbonitrile
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	PKCθ 8 nM (IC50)
ln Vitro	CC-90005 demonstrates the exceptional selectivity of CC-90005, with IC50s greater than 3 μM for every other family member[1]. CYP2C9 (IC50=8 μM) and CYP2C19 (IC50=5.9 μM) in human liver microsomes are both moderately inhibited by CC-90005[1]. In human PBMCs containing LRS_WBC, CC-90005 suppresses IL-2 expression, with an IC50 of 0.15 μM[1]. PBMCs treated with CC-90005 (1–10 μM; 24 h) exhibit 51% and 88% inhibition, respectively, of T cell proliferation[1].
ln Vivo	In a model of chronic T cell activation, CC-90005 (3-30 mg/kg; po twice daily for 4 days) significantly reduces the size of the popliteal lymph node (PLN)[1]. A single po dose of CC-90005 (100 mg/kg) significantly reduces the release of IL-2 from the spleen and plasma by 54% and 51%, respectively[1]. In rats and dogs, respectively, CC-90005 demonstrates a respectable oral bioavailability (66 and 46%) and Cmax (1.18 and 1.2 μM) after oral administration (10 and 3 mg/kg)[1]. In rats and dogs, respectively, CC-90005 displays the mean residence time (0.52 and 2.0 h), CL (69.1 and 20.5 mL/min/kg), and Vss (2.11 and 2.44 L/kg) after intravenous administration (2 and 1 mg/kg).
Animal Protocol	Animal/Disease Models: B6D2F1 mice (20 g) were injected with allogeneic spleen cells Doses: 3, 10, 30 mg/kg Route of Administration: Po twice (two times) daily for 4 days Experimental Results: Inhibited PLN size by 45 and 38% at doses of 10 and 30 mg/kg, respectively.
References	[1]. Discovery of the Selective Protein Kinase C-θ Kinase Inhibitor, CC-90005. J Med Chem. 2021 Aug 26;64(16):11886-11903.

Solubility Data

Solubility (In Vitro)

DMSO : 62.5 mg/mL (139.67 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.25 mg/mL (2.79 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 12.5 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: ≥ 1.25 mg/mL (2.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 12.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 1.25 mg/mL (2.79 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 12.5 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	2.2347 mL	11.1737 mL	22.3474 mL
	5 mM	0.4469 mL	2.2347 mL	4.4695 mL
	10 mM	0.2235 mL	1.1174 mL	2.2347 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.