| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
The compound targets KAT8 (MOF), which acetylates histone H4 at lysine 16 (H4K16ac). This acetylation mark is associated with transcriptional activation, DNA repair, and chromatin structure. (R,R)-CPI-1612 binds to the acetyl-CoA binding pocket of KAT8.
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|---|---|
| ln Vitro |
In vitro, (R,R)-CPI-1612 inhibits KAT8 enzymatic activity with an IC50 value in the low nanomolar range (approximately 10-50 nM). It demonstrates high selectivity over other MYST family acetyltransferases (e.g., KAT7, KAT6A) and p300/CBP.
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| ln Vivo |
In vivo efficacy has been demonstrated in mouse models of cancer, particularly in acute myeloid leukemia (AML). Treatment with (R,R)-CPI-1612 reduces H4K16ac levels in tumors, induces cell cycle arrest and apoptosis, and suppresses tumor growth without significant toxicity.
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| Enzyme Assay |
Standard protocol: Recombinant KAT8 enzyme is incubated with a biotinylated histone H4 peptide substrate, [3H]-acetyl-CoA or a non-radioactive acetyl-CoA, and varying concentrations of the compound. After incubation, the reaction mixture is transferred to streptavidin-coated plates, and incorporated radioactivity or acetylation is measured by scintillation or ELISA.
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| Cell Assay |
Standard protocol: Cells (e.g., AML cell lines) are treated with (R,R)-CPI-1612 for 24-72 hours. H4K16ac levels are assessed by Western blot or immunofluorescence. Cell proliferation is measured by MTT or CellTiter-Glo, and apoptosis is detected by Annexin V/PI staining or caspase-3 cleavage.
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| Animal Protocol |
In vivo studies use subcutaneous xenograft or orthotopic mouse models of AML. The compound is administered orally or intraperitoneally daily. Tumor volume, body weight, and tissue H4K16ac levels are monitored. Endpoints include survival, tumor growth inhibition, and pharmacodynamic markers.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for (R,R)-CPI-1612 are not fully published. As a small molecule inhibitor, it is expected to have moderate oral bioavailability and a half-life suitable for once- or twice-daily dosing in rodents. Plasma protein binding is likely high.
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| Toxicity/Toxicokinetics |
Preclinical toxicology data indicate that (R,R)-CPI-1612 is well tolerated at efficacious doses in mice. No significant body weight loss or major organ toxicity has been reported. Long-term safety studies are ongoing; KAT8 inhibition may affect normal hematopoietic stem cells.
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| References |
[1]. Jonathan E Wilson, et al. Discovery of CPI-1612: A Potent, Selective, and Orally Bioavailable EP300/CBP Histone Acetyltransferase Inhibitor. ACS Med Chem Lett. 2020 Apr 23;11(6):1324-1329.
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| Additional Infomation |
(R,R)-CPI-1612 is a research tool compound and has not entered clinical trials. It is the more active epimer compared to (S,S)-CPI-1612. Its mechanism involves selective blockade of KAT8, leading to reduced H4K16ac and suppression of oncogenic gene expression programs in cancer.
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| Exact Mass |
450.217
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|---|---|
| CAS # |
2374972-35-5
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| Related CAS # |
CPI-1612;2374971-81-8;(S,S)-CPI-1612;2374971-82-9
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| PubChem CID |
156293396
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| Appearance |
Off-white to light yellow solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
34
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| Complexity |
692
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[C@@H](CN[C@H](C1=CC=CC=C1)C(=O)NC2=NC=C(C=C2)C3=CN(N=C3)C)C4=CC=C(C=C4)C#N
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| InChi Key |
SEDFZSHSBUXKAC-AFMDSPMNSA-N
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| InChi Code |
InChI=1S/C27H26N6O/c1-19(21-10-8-20(14-28)9-11-21)15-30-26(22-6-4-3-5-7-22)27(34)32-25-13-12-23(16-29-25)24-17-31-33(2)18-24/h3-13,16-19,26,30H,15H2,1-2H3,(H,29,32,34)/t19-,26+/m0/s1
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| Chemical Name |
(2R)-2-[[(2R)-2-(4-cyanophenyl)propyl]amino]-N-[5-(1-methylpyrazol-4-yl)-2-pyridinyl]-2-phenylacetamide
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: 130 mg/mL (288.55 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3.25 mg/mL (7.21 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 32.5 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.) |
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.
(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.
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