(S)-CR8 trihydrochloride, an analog of Roscovitine, is a novel, potent 2nd-generation cyclin-dependent kinase (CDK) inhibitor, also acting as a molecular glue degrader that depletes cyclin K. After experimental traumatic brain injury, it functions by reducing neuronal loss, astrocytosis, microglial activation, and neurologic dysfunction. [CDK1/cyclin B (IC50=0.09 μM), CDK2/cyclin A (0.072 μM), CDK2/cyclin E (0.041 μM), CDK5/p25 (0.11 μM), CDK7/cyclin H (1.1 μM), CDK9/cyclin T (0.18 μM), and CK1δ/ε (0.4 μM) are all inhibited by (S)-CR8. The neuroprotective effect of (R)-CR8 is accompanied by apoptosis.

Physicochemical Properties

Molecular Formula	C24H32CL3N7O
Molecular Weight	540.9162
Exact Mass	431.24
Elemental Analysis	C, 53.29; H, 5.96; Cl, 19.66; N, 18.13; O, 2.96
CAS #	1786438-30-9
Related CAS #	(R)-CR8;294646-77-8
PubChem CID	90488866
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	6
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	9
Heavy Atom Count	35
Complexity	557
Defined Atom Stereocenter Count	1
SMILES	CC[C@H](CO)NC1=NC(=C2C(=N1)N(C=N2)C(C)C)NCC3=CC=C(C=C3)C4=CC=CC=N4.Cl.Cl.Cl
InChi Key	ORYSYXHQFOWNDK-RGFWRHHQSA-N
InChi Code	InChI=1S/C24H29N7O.3ClH/c1-4-19(14-32)28-24-29-22(21-23(30-24)31(15-27-21)16(2)3)26-13-17-8-10-18(11-9-17)20-7-5-6-12-25-20;;;/h5-12,15-16,19,32H,4,13-14H2,1-3H3,(H2,26,28,29,30);3*1H/t19-;;;/m1.../s1
Chemical Name	(2R)-2-[[9-propan-2-yl-6-[(4-pyridin-2-ylphenyl)methylamino]purin-2-yl]amino]butan-1-ol;trihydrochloride
Synonyms	(S)-CR8 trihydrochloride; (S) CR8; (S)CR8 triHCl
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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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	CDK1/cyclinB1 (IC50 = 0.09 μM); cdk2/cyclin A (IC50 = 0.072 μM); CDK2/cyclinE (IC50 = 0.041 μM); Cdk5/p25 (IC50 = 0.11 μM); CDK7/cyclin H (IC50 = 1.1 μM); CDK9/Cyclin T (IC50 = 0.18 μM); CK1δ/ε (IC50 = 0.4 μM)
ln Vitro	(R)-CR8 trihydrochloride (0.1-100 μM) has an IC50 of 0.49 μM for the SH-SY5Y cell line, making it a powerful inducer of apoptotic cell death. Poly-(ADP-ribose)polymerase (PARP) cleavage is dose-dependently induced by (R)-CR8 trihydrochloride (0.25–10 μM).[2]
ln Vivo	(R)-CR8 trihydrochloride treatment with (R)-CR8 trihydrochloride reduces lesion volume, ameliorates depressive-like symptoms, and lessens sensorimotor and cognitive deficits in rats with lateral fluid percussion-induced traumatic brain injury.[3]
Cell Assay	Treatment with (R)-CR8 trihydrochloride is applied to exponentially growing cultures (0.1-100 μM or 0.25-10 μM; 48h). Appropriate DMSO dilutions are also used in control experiments. The reduction of MTS serves as a proxy for cell viability. The amount of LDH activity released during cell lysis is measured to determine cell death. Western blotting is used to determine the expression level of PARP.
Animal Protocol	lateral fluid percussion-induced traumatic brain injury rats(male; Sprague-Dawley) 5 mg/Kg i.p.
References	[1]. J Biomed Sci . 2015 Jul 17;22(1):57. [2]. Oncogene . 2008 Oct 2;27(44):5797-807. [3]. J Cereb Blood Flow Metab . 2014 Mar;34(3):502-13.

Solubility Data

Solubility (In Vitro)

DMSO: ~50 mg/mL (~92.4 mM）

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.17 mg/mL (4.01 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 21.7 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: ≥ 2.17 mg/mL (4.01 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 21.7 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: ≥ 2.17 mg/mL (4.01 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 21.7 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	1.8487 mL	9.2435 mL	18.4870 mL
	5 mM	0.3697 mL	1.8487 mL	3.6974 mL
	10 mM	0.1849 mL	0.9244 mL	1.8487 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.