Physicochemical Properties
| Molecular Formula | C17H18CLN5O2 |
| Molecular Weight | 359.810122013092 |
| Exact Mass | 359.11 |
| Elemental Analysis | C, 56.75; H, 5.04; Cl, 9.85; N, 19.46; O, 8.89 |
| CAS # | 1887237-54-8 |
| PubChem CID | 118948181 |
| Appearance | White to off-white solid powder |
| LogP | 1.5 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 25 |
| Complexity | 511 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | C[C@H]1C[C@H](C2=C(N1C(=O)C)C=CC(=C2)C(=O)N)NC3=NC=C(C=N3)Cl |
| InChi Key | KNBYFXZNSOENGW-LKFCYVNXSA-N |
| InChi Code | InChI=1S/C17H18ClN5O2/c1-9-5-14(22-17-20-7-12(18)8-21-17)13-6-11(16(19)25)3-4-15(13)23(9)10(2)24/h3-4,6-9,14H,5H2,1-2H3,(H2,19,25)(H,20,21,22)/t9-,14+/m0/s1 |
| Chemical Name | (2S,4R)-1-Acetyl-4-((5-chloropyrimidin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinoline-6-carboxamide |
| Synonyms | IBET567, I BET567, I-BET-567 |
| 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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 | BRD4 (BD1) 6.9 (pIC50) BRD2 7.2 (pIC50) |
| ln Vitro | I-BET567 (compound 27) (72 hours; 1.5 nM-30 μM), has a mean gpIC50 of 6.2 (0.63 μM) and significantly suppresses the proliferation of the human NMC cell line 11060 in vitro[1]. |
| ln Vivo | Compound 27 (I-BET567; 3, 10, and 30 mg/kg; po; once daily for 20 days) significantly inhibits the growth of tumors as compared to vehicle controls at both 10 and 30 mg/kg[1]. I-BET567's pharmacokinetic (PK) profile was evaluated in male Wistar Han rats and Beagle Dogs after oral and intravenous infusion[1]. the species dose ivb/poc (mg/kg) CLb (mL/min/kg) CLb,u (mL/min/kg) CLrenal (mL/min/kg) Vss (L/kg) Vss,u (L/kg) t1/2 (h) Fpo (%) fub rat 1.3/3 25 109 7 2.4 10.4 1.6 99d 0.23 dog 1.0/3 8.1 20 6.9 1.2 2.9 1.8 98 0.41 a: Unless otherwise noted, values are mean, n=3. b: An intravenous dose of 10%, w/v Kleptose HPB in saline (2 %: 98% (v/v)) infusion for one hour in DMSO. c: 1% (w/v) methycellulose (400 cps) (aq) is the PO dosage vehicle. d: Average of n is 2. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: NMC line 11060 cells Tested Concentrations: 1.5 nM-30 μM Incubation Duration: 72 hrs (hours) Experimental Results: Dramatically decreased cell growth. |
| Animal Protocol |
Animal/Disease Models: NMC 11060 xenograft mouse model (NOD/SCID mouse; bearing NMC 11060 cells) [1] Doses: 3, 10, and 30 mg/kg Route of Administration: po (one time/day for 20 days Experimental Results: Led to a significant reduction in tumor growth compared to vehicle controls at both 10 and 30 mg/kg. |
| References |
[1]. Design, Synthesis, and Characterization of I-BET567, a Pan-Bromodomain and Extra Terminal (BET) Bromodomain Oral Candidate [published online ahead of print, 2022 Jan 7]. |
Solubility Data
| Solubility (In Vitro) | DMSO : 100 mg/mL (277.92 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.95 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 25.0 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: ≥ 2.5 mg/mL (6.95 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 25.0 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: ≥ 2.5 mg/mL (6.95 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 25.0 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 | 2.7792 mL | 13.8962 mL | 27.7924 mL | |
| 5 mM | 0.5558 mL | 2.7792 mL | 5.5585 mL | |
| 10 mM | 0.2779 mL | 1.3896 mL | 2.7792 mL |