CC214-2 is an orally bioavailable mTOR kinase inhibitor. CC214-2 targets mTORC1 (pS6) and mTORC2 (pAktS473). CC214-2 induces autophagy, a potential target for host-directed therapy (HDT) of tuberculosis (TB). CC214-2 displays synergistic bacteriostatic (inhibition of bacterial growth) and bactericidal ( bacteria killing) activity against tuberculosis (TB) and shortens the time to efficacy. CC214-2 also inhibits rapamycin resistance signaling and inhibits glioblastoma growth in vitro & in vivo.

Physicochemical Properties

Molecular Formula	C20H25N5O3
Molecular Weight	383.444204092026
Exact Mass	383.195
CAS #	1228012-18-7
PubChem CID	58298312
Appearance	Light yellow to light brown solid powder
LogP	0.5
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	4
Heavy Atom Count	28
Complexity	554
Defined Atom Stereocenter Count	0
SMILES	O1CCC(CN2C3C(=NC=C(C4=CN=C(C=C4)C(C)(C)O)N=3)NC(C2)=O)CC1
InChi Key	UWUPKVZQISLSSA-UHFFFAOYSA-N
InChi Code	InChI=1S/C20H25N5O3/c1-20(2,27)16-4-3-14(9-21-16)15-10-22-18-19(23-15)25(12-17(26)24-18)11-13-5-7-28-8-6-13/h3-4,9-10,13,27H,5-8,11-12H2,1-2H3,(H,22,24,26)
Chemical Name	2-[6-(2-hydroxypropan-2-yl)pyridin-3-yl]-8-(oxan-4-ylmethyl)-5,7-dihydropyrazino[2,3-b]pyrazin-6-one
Synonyms	CC214 2; CC214-2; CC2142
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

ln Vivo	In PC3 tumor xenograft models, CC214-2 (25 mg/kg, 50 mg/kg; buccal; once daily for 21 days) reduces tumor volume [1]. U87EGFRvIII flank xenograft growth in mice was significantly reduced by CC214-2 (30 mg/kg, 100 mg) CC214-2 (30 mg/kg; wall) in addition to reducing foam foam CFU and preventing numbers CC214-2 (50 mg/kg; sidewall; once daily for 6 days) [2].
Animal Protocol	Animal/Disease Models: Mouse U87EGFRvIII flank xenografts [2] (100 mg/kg; lateral wall; every 2 days for 6 days) inhibits mTORC1 and mTORC2 signaling in an intracranial astroblastoma model [2]. 50 mg/kg Route of Administration: Oral; one time/day for 6 days Experimental Results: Inhibition of tumor growth. Autophagy was similarly activated in U87EGFRvIII xenografts.
References	[1]. The mTOR kinase inhibitors, CC214-1 and CC214-2, preferentially block the growth of EGFRvIII-activated glioblastomas. Clin Cancer Res. 2013 Oct 15;19(20):5722-32. [2]. Dual mTORC1/mTORC2 Inhibition as a Host-Directed Therapeutic Target in Pathologically Distinct Mouse Models of Tuberculosis. Antimicrob Agents Chemother. 2021;65(7):e0025321.

Solubility Data

Solubility (In Vitro)

DMSO : ~12.5 mg/mL (~32.60 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.25 mg/mL (3.26 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 (3.26 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.6080 mL	13.0398 mL	26.0797 mL
	5 mM	0.5216 mL	2.6080 mL	5.2159 mL
	10 mM	0.2608 mL	1.3040 mL	2.6080 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.