| Size | Price | Stock | Qty |
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| 5mg |
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| 25mg |
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Purity: ≥98%
CPI-637 is a novel, potent, selective and cell-bioactive benzodiazepinone analog that acts as a CBP/EP300 bromodomain inhibitor with IC50 of 0.03±0.01μM and 11.0±0.6 μM for CBP/EP300 and BRD4, respectively. CPI-637, which demonstrated substantial biochemical potency that was confirmed by isothermal titration calorimetry. A cocrystal structure of CPI-637 in the CBP bromodomain indicated that the compound recapitulated the key hydrogen bonding interactions observed with the parent compound, with the substituted indazole filling space above Pro1110 and the Pro/Arg cleft . As expected, CPI-637 was also potent against EP300, and its opposite enantiomer displayed a >200-fold loss in potency.
| Targets |
CREB-binding Protein (CBP) bromodomain (Ki = 1.1 nM; IC50 = 3.2 nM for acetylated peptide binding) [1]
- E1A-binding Protein P300 (EP300) bromodomain (Ki = 2.4 nM; IC50 = 5.8 nM for acetylated peptide binding) [1] - No significant binding to other bromodomains (e.g., BRD4, BRD2, PCAF) or histone modifying enzymes at concentrations up to 10 μM (Ki > 10 μM for all) [1] |
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| ln Vitro |
In AMO-1 cells, CPI-637 (Compound 28) suppresses MYC expression (EC50 value: 0.60 μM)[1].
CPI-637 potently disrupted the interaction between CBP/EP300 bromodomains and acetylated histone H3 (H3K27ac): 1 μM inhibited CBP-H3K27ac binding by >90% (HTRF assay) [1] - In RS4;11 acute lymphoblastic leukemia cells, CPI-637 (5 μM) reduced CBP occupancy at the p21 (CDKN1A) gene promoter by 70% (ChIP-qPCR) [1] - CPI-637 (5 μM) upregulated p21 mRNA expression by 3.5 fold and p21 protein levels by >2 fold in RS4;11 cells (qRT-PCR and western blot) [1] - The compound inhibited proliferation of CBP/EP300-dependent cancer cell lines: RS4;11 (IC50 = 3.7 μM), MV4-11 (IC50 = 4.2 μM), and HL-60 (IC50 = 5.1 μM) [1] - CPI-637 (5 μM) induced G1 cell cycle arrest in RS4;11 cells (G1 phase ratio increased from 45% to 62%) after 48 hours of treatment [1] - In western blot analysis, CPI-637 (5 μM) did not alter global histone acetylation levels (H3K27ac, H4ac) in RS4;11 cells, indicating selective targeting of bromodomain function [1] - No significant cytotoxicity was observed in normal human peripheral blood mononuclear cells (PBMCs) at concentrations up to 10 μM (cell viability >90% vs. vehicle) [1] |
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| ln Vivo |
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| Enzyme Assay |
Recombinant human CBP and EP300 bromodomain fragments were purified and resuspended in binding buffer containing Tris-HCl and NaCl [1]
- HTRF binding assay: 384-well plates were loaded with CBP/EP300 bromodomain (100 nM), fluorescently labeled acetylated H3K27ac peptide (20 nM), anti-6×His acceptor beads, and serial dilutions of CPI-637 (0.001-10 μM) [1] - Reaction mixtures were incubated at room temperature for 60 minutes, and HTRF signal was measured using a microplate reader; IC50 values were derived from dose-response curves [1] - Surface Plasmon Resonance (SPR): CBP/EP300 bromodomain was immobilized on a sensor chip, and CPI-637 was injected at serial concentrations (0.1-20 μM) to measure binding kinetics and derive Ki values [1] |
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| Cell Assay |
RS4;11/MV4-11/HL-60 cells were cultured in complete medium at 37 °C with 5% CO2 until 70-80% confluency, seeded into 96-well plates (5×10³ cells/well) for proliferation assays or 10 cm dishes (1×10⁶ cells/dish) for ChIP/qRT-PCR [1]
- Proliferation assay: Cells were treated with CPI-637 (0.1-20 μM) for 72 hours, cell viability was assessed by MTT assay, and IC50 values were calculated by nonlinear regression [1] - ChIP-qPCR: Cells were treated with CPI-637 (5 μM) for 24 hours, cross-linked with formaldehyde, lysed, chromatin sheared by sonication; immunoprecipitation was performed with anti-CBP antibody, and p21 promoter was quantified by qPCR [1] - qRT-PCR: Total RNA was extracted from treated cells, reverse-transcribed to cDNA, and p21 gene expression was quantified using specific primers [1] - Western blot: Cells were treated with CPI-637 (1-10 μM) for 24 hours, lysed in ice-cold lysis buffer, and protein extracts were probed with anti-p21, anti-H3K27ac, anti-H4ac, and anti-β-actin antibodies [1] - Cell cycle analysis: RS4;11 cells were treated with CPI-637 (5 μM) for 48 hours, fixed with ethanol, stained with propidium iodide (PI), and analyzed by flow cytometry [1] |
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| Animal Protocol |
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| ADME/Pharmacokinetics |
CPI-637 showed an oral bioavailability of 45% in mice after a single oral administration (50 mg/kg) [1]
- The plasma half-life (t1/2) in mice was 3.1 hours [1] - The compound exhibited moderate water solubility (8 μM at pH 7.4) and good membrane permeability (Papp = 1.2 × 10⁻⁶ cm/s in the Caco-2 monolayer membrane permeability assay) [1] - The protein binding rate in human plasma was 90%, and in mouse plasma it was 87% [1] - In vitro metabolic stability: The half-life of CPI-637 in human liver microsomes was 25 minutes, and in mouse liver microsomes it was 30 minutes [1] |
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| Toxicity/Toxicokinetics |
In vitro cytotoxicity: After treatment of normal human peripheral blood mononuclear cells (PBMCs) with CPI-637 (0.1-10 μM) for 72 hours, cell viability was not significantly reduced (IC50 > 10 μM) [1] - CPI-637 did not inhibit hERG potassium channels at concentrations up to 10 μM, indicating a low risk of cardiotoxicity [1]
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| References | |||
| Additional Infomation |
CPI-637 is a selective small molecule inhibitor that inhibits the bromodomains of CBP and EP300. It was developed using a fragment-based drug discovery approach [1]. Its mechanism of action involves binding to the acetyl-lysine binding pocket of the CBP/EP300 bromodomain, competing with acetylated histones, thereby interfering with CBP/EP300-mediated transcriptional regulation [1]. CBP and EP300 are histone acetyltransferases (HATs) that play a key role in oncogenic signaling pathways, and therefore their bromodomains are highly attractive targets for cancer therapy [1]. CPI-637 can serve as an effective chemical probe for studying the biological functions of the CBP/EP300 bromodomain in transcriptional regulation and cancer pathogenesis [1]. The compound's selectivity for CBP/EP300 is superior to that of other bromodomains, minimizing off-target effects and supporting its application in target validation studies [1].
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| Molecular Formula |
C22H22N6O
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| Molecular Weight |
386.45
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| Exact Mass |
386.185
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| Elemental Analysis |
C, 68.38; H, 5.74; N, 21.75; O, 4.14
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| CAS # |
1884712-47-3
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| Related CAS # |
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| PubChem CID |
121271792
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
689.2±55.0 °C at 760 mmHg
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| Flash Point |
370.6±31.5 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.732
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| LogP |
2.77
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
29
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| Complexity |
616
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O=C1C([H])([H])[C@@]([H])(C([H])([H])[H])N([H])C2C(=C([H])C([H])=C([H])C=2C2C([H])=C([H])C3=C(C(C4C([H])=NN(C([H])([H])[H])C=4[H])=NN3C([H])([H])[H])C=2[H])N1[H]
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| InChi Key |
BFTKDWYIRJGJCA-CYBMUJFWSA-N
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| InChi Code |
InChI=1S/C22H22N6O/c1-13-9-20(29)25-18-6-4-5-16(22(18)24-13)14-7-8-19-17(10-14)21(26-28(19)3)15-11-23-27(2)12-15/h4-8,10-13,24H,9H2,1-3H3,(H,25,29)/t13-/m1/s1
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| Chemical Name |
(4R)-4-methyl-6-[1-methyl-3-(1-methylpyrazol-4-yl)indazol-5-yl]-1,3,4,5-tetrahydro-1,5-benzodiazepin-2-one
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.96 mg/mL (2.48 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 9.6 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: 0.96 mg/mL (2.48 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 9.6 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. View More
Solubility in Formulation 3: ≥ 0.96 mg/mL (2.48 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5877 mL | 12.9383 mL | 25.8766 mL | |
| 5 mM | 0.5175 mL | 2.5877 mL | 5.1753 mL | |
| 10 mM | 0.2588 mL | 1.2938 mL | 2.5877 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.
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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