For research use only. Not for therapeutic Use.
UMI-77 (CAT: I003875) is a small molecule inhibitor that targets the anti-apoptotic proteins Mcl-1 and Bcl-2. Mcl-1 and Bcl-2 are members of the Bcl-2 family of proteins that play a crucial role in regulating apoptosis (programmed cell death). UMI-77 selectively binds to Mcl-1 and Bcl-2, inhibiting their interaction with pro-apoptotic proteins and promoting apoptosis in cancer cells. This targeted inhibition of Mcl-1 and Bcl-2 can be beneficial in the treatment of cancer, as overexpression of these proteins is often associated with cancer cell survival and resistance to chemotherapy. UMI-77 shows promise as a potential anticancer agent, particularly in cancers where Mcl-1 and Bcl-2 play a significant role in promoting cell survival.
| Catalog Number | I003875 |
| CAS Number | 518303-20-3 |
| Synonyms | 2-[4-[(4-bromophenyl)sulfonylamino]-1-hydroxynaphthalen-2-yl]sulfanylacetic acid |
| Molecular Formula | C₁₈H₁₄BrNO₅S₂ |
| Purity | ≥95% |
| Target | Bcl-2 Family |
| Solubility | DMSO: ≥ 30 mg/mL |
| Storage | Store at -20°C |
| IC50 | 490 nM (Ki, for Mcl-1) |
| InChI | InChI=1S/C18H14BrNO5S2/c19-11-5-7-12(8-6-11)27(24,25)20-15-9-16(26-10-17(21)22)18(23)14-4-2-1-3-13(14)15/h1-9,20,23H,10H2,(H,21,22) |
| InChIKey | WUGANDSUVKXMEC-UHFFFAOYSA-N |
| SMILES | C1=CC=C2C(=C1)C(=CC(=C2O)SCC(=O)O)NS(=O)(=O)C3=CC=C(C=C3)Br |
| Reference | 1:Mol Cell Biochem. 2017 Mar 23. doi: 10.1007/s11010-017-2997-x. [Epub ahead of print] UMI-77 primes glioma cells for TRAIL-induced apoptosis by unsequestering Bim and Bak from Mcl-1.Liu JW,Zhu ZC,Li K,Wang HT,Xiong ZQ,Zheng J, PMID: 28337703 DOI: 10.1007/s11010-017-2997-x </br><span>Abstract:</span> Malignant glioma is the most common and aggressive form of brain tumor with poor prognosis of survival. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent but is insufficient of inducing apoptosis in some types of gliomas. In this study, we showed that the small-molecule Mcl-1 inhibitor UMI-77 sensitized glioma cells to TRAIL treatment, as evidenced by cell viability assay, Annexin V staining and JC-1 staining. Combination of UMI-77 and TRAIL in glioma cells led to the activation of caspase-8 and Bid, cleavage of caspase-3 and poly-ADP ribose polymerase (PARP), accumulation of tBid in the mitochondria and release of cytochrome c into the cytosol. UMI-77 alone or in combination with TRAIL untethered pro-apoptotic Bcl-2 proteins Bim and Bak from the sequestration of Mcl-1 and promoted the conformational activation of Bak. Small hairpin RNA (shRNA) of Bid attenuated the cleavage of caspase-8, Bid, caspase-3 and PARP, and reduced the cytotoxicity of UMI-77 plus TRAIL as compared with control shRNA cells, indicating this synergy entails the crosstalk between extrinsic and intrinsic apoptotic signaling. Taken together, UMI-77 enhances TRAIL-induced apoptosis by unsequestering Bim and Bak, which provides a novel therapeutic strategy for the treatment of gliomas. |
