AZD4320 is a novel, potent BH3-mimic and dual inhibitor of BCL2/BCLxL with IC50s of 26 nM, 17 nM, and 170 nM for KPUM-MS3, KPUM-UH1, and STR-428 cells, respectively. Despite recent therapeutic advancements, the prognosis for diffuse large B-cell lymphomas (DLBCLs) that concurrently overexpress c-MYC and BCL2, also known as double hit lymphoma (DHL) and double expressing lymphoma (DEL), is still poor. By increasing the number of cells going through apoptosis in all three of the tested cell lines, AZD4320 and AZD5153 had an antitumor effect that was primarily synergistic. These findings support the dual targeting of BRD4 and BCL2 by AZD5153 and AZD4320 as a therapeutic approach against DHL and DEL.
Physicochemical Properties
| Molecular Formula | C45H48CLF3N4O7S3 |
| Molecular Weight | 945.528437614441 |
| Exact Mass | 944.23 |
| Elemental Analysis | C, 57.16; H, 5.12; Cl, 3.75; F, 6.03; N, 5.93; O, 11.84; S, 10.17 |
| CAS # | 1357576-48-7 |
| Related CAS # | 1357576-49-8 (formate);1357576-48-7; |
| PubChem CID | 86661883 |
| Appearance | White to off-white solid powder |
| LogP | 9.3 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 14 |
| Rotatable Bond Count | 18 |
| Heavy Atom Count | 63 |
| Complexity | 1630 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | CN(CC[C@H](CSC1=CC=CC=C1)NC2=C(C=C(C=C2)S(=O)(=O)NC(=O)C3=CC=C(C=C3)N4CCC(CC4)[C@H](C5=CC=CC=C5C6=CC=C(C=C6)Cl)O)S(=O)(=O)C(F)(F)F)CCO |
| InChi Key | UNEJSHNDABUZNY-UJNHCCGESA-N |
| InChi Code | InChI=1S/C45H48ClF3N4O7S3/c1-52(27-28-54)24-23-35(30-61-37-7-3-2-4-8-37)50-41-20-19-38(29-42(41)62(57,58)45(47,48)49)63(59,60)51-44(56)33-13-17-36(18-14-33)53-25-21-32(22-26-53)43(55)40-10-6-5-9-39(40)31-11-15-34(46)16-12-31/h2-20,29,32,35,43,50,54-55H,21-28,30H2,1H3,(H,51,56)/t35-,43-/m1/s1 |
| Chemical Name | 4-[4-[(R)-[2-(4-chlorophenyl)phenyl]-hydroxymethyl]piperidin-1-yl]-N-[4-[[(2R)-4-[2-hydroxyethyl(methyl)amino]-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylbenzamide |
| Synonyms | AZD4320; AZD-4320; AZD 4320 |
| 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) |
Biological Activity
| Targets | BCL2 (IC50 = 17 nM); BCLxL (IC50 = 17 nM) |
| ln Vitro | AZD4320 potently enhances the antitumor effect of AZD5153 in double expressing lymphoma (DEL)- and double hit lymphoma (DHL)-derived cell lines in a dose-dependent manner. On DEL- and DHL-derived cell lines, AZD4320 primarily exhibits synergistic and at least additive growth inhibitory effects, and it significantly increases the number of cells undergoing apoptosis in all three cell lines[1]. |
| Cell Assay | KPUM-MS3 and KPUM-UH1 are two DEL-derived cell lines, and STR-428 is a DHL-derived cell line. Cells are treated with five concentrations of AZD4320 (0.25, 0.5, 1.0, 2.0, and 4.0IC50) for 72 hours, and then the results are measured using a modified MTT assay[1]. |
| References |
[1]. Dual targeting of bromodomain-containing 4 by AZD5153 and BCL2 by AZD4320 against B-cell lymphomas concomitantly overexpressing c-MYC and BCL2. Invest New Drugs. 2018 Jun 21. |
Solubility Data
| Solubility (In Vitro) | DMSO: ~100 mg/mL (~105.8 mM） |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (6.61 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 62.5 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0576 mL | 5.2880 mL | 10.5761 mL | |
| 5 mM | 0.2115 mL | 1.0576 mL | 2.1152 mL | |
| 10 mM | 0.1058 mL | 0.5288 mL | 1.0576 mL |