(S)-CR8

Alias: (S)-CR8 (S) CR8 (S)CR8

Cat No.:V6855 Purity: ≥98%

COA Product Data Instructions for use SDS

(S)-CR8, ananalog of Roscovitine, is a novel, potent 2nd-generation cyclin-dependent kinase (CDK) inhibitor, also acting as a molecular glue degrader that depletes cyclin K.

(S)-CR8 Chemical Structure CAS No.: 1084893-56-0
Product category: New1

This product is for research use only, not for human use. We do not sell to patients.

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1-708-310-1919 sales@invivochem.com

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Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

(S)-CR8, 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. It acts by limiting microglial activation, astrocytosis, neuronal loss, and neurologic dysfunction after experimental traumatic brain injury. (S)-CR8 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 induces apoptosis and has neuroprotective effect.

Biological Activity I Assay Protocols (From Reference)

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].S\u0142abicki 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. [4].Casein kinase 1\u03b5 and 1\u03b1 as novel players in polycystic kidney disease and mechanistic targets for (R)-roscovitine and (S)-CR8. Am J Physiol Renal Physiol. 2018 Mar 14.
Additional Infomation	(2S)-2-[[9-propan-2-yl-6-[[4-(2-pyridinyl)phenyl]methylamino]-2-purinyl]amino]-1-butanol is a phenylpyridine.

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].S\u0142abicki 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.

[4].Casein kinase 1\u03b5 and 1\u03b1 as novel players in polycystic kidney disease and mechanistic targets for (R)-roscovitine and (S)-CR8. Am J Physiol Renal Physiol. 2018 Mar 14.

Additional Infomation

(2S)-2-[[9-propan-2-yl-6-[[4-(2-pyridinyl)phenyl]methylamino]-2-purinyl]amino]-1-butanol is a phenylpyridine.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Exact Mass	431.243
CAS #	1084893-56-0
Related CAS #	(R)-CR8;294646-77-8
PubChem CID	25211051
Appearance	Typically exists as solid at room temperature
LogP	3.759
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	9
Heavy Atom Count	32
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
InChi Key	ULEOUNVVBPZETL-SFHVURJKSA-N
InChi Code	InChI=1S/C24H29N7O/c1-5-18(14-32)27-24-28-22(21-23(29-24)31(15-26-21)16(2)3)30(4)19-11-9-17(10-12-19)20-8-6-7-13-25-20/h6-13,15-16,18,32H,5,14H2,1-4H3,(H,27,28,29)/t18-/m0/s1
Chemical Name	(S)-2-((9-isopropyl-6-(methyl(4-(pyridin-2-yl)phenyl)amino)-9H-purin-2-yl)amino)butan-1-ol
Synonyms	(S)-CR8 (S) CR8 (S)CR8
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)

Solubility Data

Solubility (In Vitro)	May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
Solubility (In Vivo)	Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2:* DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] 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. Injection Formulation 5:* 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.)

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

Injection Formulations
(e.g. IP/IV/IM/SC)

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

Oral Formulations

Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

(Please use freshly prepared in vivo formulations for optimal results.)

Calculator

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

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The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

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Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
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Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

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The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

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Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

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Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Clinical Trial Information

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT01687075	COMPLETED	Device: CR8 a drug eluting coronary stent	A Total Number of 200 Patients Fulfilling the Selection Angioplasty of de Novo Lesion(s) in Native Coronary Arteries Should be Screened for Eligibility. Consecutive Subjects Who Are Suitable for a Coronary	Tel-Aviv Sourasky Medical Center	2012-10	Not Applicable
NCT01659437	COMPLETED	Drug: Clarithromycin Extended Release Drug: Streptomycin intramuscular injection	Mycobacterium Ulcerans Infection	University Medical Center Groningen	2012-12	Phase 2 Phase 3

Biological Data

Systemic administration of CR8 inhibits lateral fluid percussion (LFP)-induced neuronal cell cycle activation (CCA). Immunocytochemistry for assessment of CCA at 24 hours after LFP. (A) Representative confocal images (scale bar, 50 μm) for G2/M-phase transition marker, cyclin G1 (green) and neuronal marker, NeuN (red) showed increased expression of cyclin G1 in neurons within the central area of the lesion in LFP-injured (LFP(vehicle (VEH))) rats, which appeared to be reduced in CR8-treated group (LFP(CR8)). (B) Semi-quantitative assessment revealed a significant decrease in the number of cyclin G1-positive cells (% sham) in CR8-treated rats (+P<0.05, versus vehicle). Analysis by one-tailed unpaired Student's t-test. Mean±s.e.m. (C) Representative confocal images (scale bar, 50 μm) for the CCA marker, proliferating cell nuclear antigen (PCNA) (green) and neuronal nuclei (NeuN) (red) showed increased expression of PCNA in neurons at the lesion site in LFP-injured rats, whereas the CR8-treated rats had reduced PCNA expression in the corresponding region.[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.

CR8 treatment reduces lateral fluid percussion (LFP)-induced lesion volume and progressive neuronal cell loss in the hippocampus, cortex, and thalamus. (A) Unbiased stereological assessment of lesion volume at 28 days post LFP was performed on Cresyl violet-stained brain sections. The stained brain sections from CR8-treated rats revealed tissue sparing. (B) Lesion volume estimation. CR8-treated rats had reduced (+++P<0.001, versus vehicle) lesion size at 28 days. Analysis by one-tailed unpaired Student's t-test. Mean±s.e.m.; n=6 to 7 per group. (C) Fluoro-Jade B staining for assessment of neuronal degeneration at 24 hours post LFP. The representative confocal images (scale bar, 1000 μm) demonstrated significant neurodegeneration in LFP-injured (LFP(vehicle, (VEH))) rats, particularly around the lesion site, as compared with CR8-treated (LFP(CR8)) rats. (D) Semi-quantitative assessment revealed attenuation of number of Fluoro-Jade B-positive cells (% sham) by CR8 treatment (+P=0.003, versus vehicle). Analysis by one-tailed unpaired Student's t-test. Mean±s.e.m. n=4 to 5 per group. [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.

CR8 treatment modulates lateral fluid percussion (LFP)-induced cortical microglial activation. (A) Representative immunohistochemical images and Neurolucida reconstructions (scale bar, 50 μm) of ramified (i), hypertrophic (ii) and bushy (iii) microglia illustrate the different morphologic features of each microglial phenotype. (B–D) Unbiased stereological quantification of microglial cell number and activation status in the cortex at 24 hours, 7 days, and 28 days. Ramified (B), hypertrophic (C), and bushy (D) microglial activation phenotypes were analyzed. There was a significant decrease in ramified microglia in vehicle-treated samples (LFP(vehicle (VEH))) at 28 days when compared with sham controls (*P<0.05, versus sham, B). Lateral fluid percussion resulted in a significant increase in hypertrophic microglia that peaked at 7 days followed by a return toward control levels by 28 days (*P<0.001, versus sham, C) and CR8 treatment (LFP(CR8)) caused significant attenuation in numbers of hypertrophic microglia at 7 days (+++P<0.05, versus vehicle, C). Lateral fluid percussion also resulted in a significant elevation in bushy microglial numbers and although the peak was reached at 7 days (***P<0.001, versus sham, aP<0.05, versus 24 hour LFP-injured samples, D), the levels remained high when compared with sham-operated samples through 28 days (*P<0.05, versus sham, bP<0.05, versus 7 day LFP-injured samples, D).[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.