(R)-CR8 trihydrochloride

(R)-CR8 (CR8) trihydrochloride, a second-generation analog of Roscovitine, is a potent CDK1/2/5/7/9 inhibitor. (R)-CR8 trihydrochloride inhibits 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). (R)-CR8 trihydrochloride induces apoptosis and has neuroprotective effect. (R)-CR8 trihydrochloride acts as a molecular glue degrader that depletes cyclin K.

Product information

CAS Number: 1786438-30-9

Molecular Weight: 540.92

Formula: C24H32Cl3N7O

Synonym:

(R)-Isomer trihydrochloride

Chemical Name: (2R)-2-{[9-(propan-2-yl)-6-({[4-(pyridin-2-yl)phenyl]methyl}amino)-9H-purin-2-yl]amino}butan-1-ol trihydrochloride

Smiles: Cl.Cl.Cl.CC(C)N1C=NC2C1=NC(N[C@@H](CO)CC)=NC=2NCC1C=CC(=CC=1)C1=CC=CC=N1

InChiKey: ORYSYXHQFOWNDK-RGFWRHHQSA-N

InChi: 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

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 62.5 mg/mL (115.54 mM; Need ultrasonic)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

(R)-CR8 (CR8) trihydrochloride (0.1-100 μM; 48 hours) is a potent inducer of apoptotic cell death with an IC50 of 0.49 μM for SH-SY5Y cell line. (R)-CR8 trihydrochloride (0.25-10 μM) induces a dose-dependent induction of poly-(ADP-ribose)polymerase (PARP) cleavage. The CDK-bound form of (R)-CR8 trihydrochloride has a solvent-exposed pyridyl moiety that induces the formation of a complex between CDK12-cyclin K and the CUL4 adaptor protein DDB1, bypassing the requirement for a substrate receptor and presenting cyclin K for ubiquitination and degradation

In Vivo:

(R)-CR8 trihydrochloride (5 mg/Kg; i.p.) results in a significant reduction in lesion size at 28 days in histological assessment.

References:

1. Bettayeb K, et al. CR8, a potent and selective, roscovitine-derived inhibitor of cyclin-dependent kinases. Oncogene. 2008 Oct 2;27(44):5797-807.
2. Kabadi SV, et al. CR8, a novel inhibitor of CDK, limits microglial activation, astrocytosis, neuronal loss, and neurologic dysfunction after experimental traumatic brain injury. J Cereb Blood Flow Metab. 2014 Mar;34(3):502-13.
3. Słabicki M, et al. The CDK inhibitor CR8 acts as a molecular glue degrader that depletes cyclin K [published online ahead of print, 2020 Jun 3]. Nature. 2020;10.1038/s41586-020-2374-x.

Products are for research use only. Not for human use.