UMI-77Mcl-1 inhibitor, novel CAS# 518303-20-3 |
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| Cas No. | 518303-20-3 | SDF | Download SDF |
| PubChem ID | 992586 | Appearance | Powder |
| Formula | C18H14BrNO5S2 | M.Wt | 468.34 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | Soluble in DMSO > 10 mM | ||
| Chemical Name | 2-[4-[(4-bromophenyl)sulfonylamino]-1-hydroxynaphthalen-2-yl]sulfanylacetic acid | ||
| SMILES | C1=CC=C2C(=C1)C(=CC(=C2O)SCC(=O)O)NS(=O)(=O)C3=CC=C(C=C3)Br | ||
| Standard InChIKey | WUGANDSUVKXMEC-UHFFFAOYSA-N | ||
| Standard 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) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | UMI-77 is a selective Mcl-1 inhibitor, which shows high binding affinity to Mcl-1 (IC50=0.31 μM). UMI-77 binds to the BH3 binding groove of Mcl-1 with Ki of 490 nM, showing selectivity over other members of anti-apoptotic Bcl-2 members.In Vitro:Competitive binding curve of UMI-77 against Mcl-1 is obtained by FP based binding assay using fluorescent labeled Bid BH3 peptide with an IC50 of 1.87±0.22 μM. UMI-77 potently inhibits the cell growth of BxPC-3 and Panc-1 cell lines with IC50 values of 3.4 μM and 4.4 μM respectively, and shows 3 to 5 times less potency in inhibition of the cell growth of two other tested cell lines MiaPaCa-2 (12.5 μM) and AsPC-1 (16.1 μM). The cell growth inhibition potency of UMI-77 correlates with the highest expression of Mcl-1 and Bak, and lowest expression of Bcl-xL in the sensitive cell lines, BxPC-3 and Panc-1. Capan-2 cells are showing similar sensitivity to UMI-77 (IC50 of 5.5 μM) as BxPC-3 and Panc-1, although has low Mcl-1 levels[1]In Vivo:UMI-77 exhibits moderate metabolic stability with a half-life of 45 minutes.The maximum tolerated dose (MTD) of UMI-77 in SCID mice is determined. Administered 60 mg/kg i.v. for 5 consecutive days per week for two weeks does not cause any loss in the animal weight and there is no obvious sign of toxicity during the course of the treatment. Increasing the dose to 80 mg/kg show severe animal weight loss (>20%), therefore 60 mg/kg is used as a therapeutic dose for the in vivo efficacy studies. Daily treatment with UMI-77 for 5 consecutive days a week for two weeks results in statistically significant tumor growth inhibition by 65% and 56% in comparison with the controls in day 19 (p<0.0001) and day 22 (p<0.003) respectively[1] References: | |||||
| Cell experiment [1]: | |
| Cell lines | Pancreatic cancer (PC) cells |
| Preparation method | Limited solubility. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
| Reacting condition | ~24 h |
| Applications | UMI-77 inhibits growth of PC cells, especially for the BxPC-3 and Panc-1 cell line with highest potency. In Panc-1 cells, UMI-77 also effectively induces apoptosis in a time-dependent and dose-dependent manner. Moreover, it leads to a dose-dependent release of cytochrome c and Smac from mitochondria. In addition, the growth inhibition and apoptosis effects of UMI-77 is abrogated by knocking down Mcl-1 expression |
| Animal experiment [1]: | |
| Animal models | BxPC-3 xenograft model in SCID mice |
| Dosage form | 60 mg/kg i.v. |
| Application | UMI-77 treatment for 5 consecutive days a week for two weeks significantly inhibits the tumor growth by 65% and 56%. UMI-77 also markedly increases the positive apoptotic cells of tumor sections comparing with the control cohorts. |
| Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
| References: 1. Abulwerdi F, Liao C, Liu M et al. A novel small-molecule inhibitor of mcl-1 blocks pancreatic cancer growth in vitro and in vivo. Mol Cancer Ther. 2014 Mar;13(3):565-75. | |
UMI-77 Dilution Calculator
UMI-77 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.1352 mL | 10.676 mL | 21.352 mL | 42.704 mL | 53.38 mL |
| 5 mM | 0.427 mL | 2.1352 mL | 4.2704 mL | 8.5408 mL | 10.676 mL |
| 10 mM | 0.2135 mL | 1.0676 mL | 2.1352 mL | 4.2704 mL | 5.338 mL |
| 50 mM | 0.0427 mL | 0.2135 mL | 0.427 mL | 0.8541 mL | 1.0676 mL |
| 100 mM | 0.0214 mL | 0.1068 mL | 0.2135 mL | 0.427 mL | 0.5338 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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UMI-77 is a novel small-molecule inhibitor of Mcl-1 with Ki and IC50 values of 0.49 μM and 0.31 μM [1].
Myeloid cell leukemia-1 (Mcl-1) is a member of the prosurvival Bcl-2 family and is a potent anti-apoptotic protein. Mcl-1 acts as an important survival factor in a broad range of human cancers [1].
UMI-77 is a novel small-molecule Mcl-1 inhibitor. In FP-based binding assays, UMI-77 potently and selectively displaced fluorescent labeled BID-BH3 peptide from Mcl-1 protein with Ki value of 0.49μM and bound to the BH3 binding pocket of Mcl-1 protein. UMI-77 bound to A1/Bfl-1, Bcl-w, Bcl-2 and Bcl-xL with Ki values of 5.33, 8.19, 23.83 and 32.99μM. In a pull-down assay, UMI-77 at 10 μM effectively and dose-dependently inhibited the interactions between BL-Noxa and cellular Mcl-1. It was reported that Mcl-1 regulates pro-apoptotic Bax and Bak proteins and preventing their pro-apoptotic activity. UMI-77 dose-dependently inhibited the binding of Mcl-1 to Bax with IC50 value of 1.43μM. In PC cells, UMI-77 inhibited cell growth and induced apoptosis in a time and dose-dependent way [1].
In BxPC-3 xenografted SCID mice model, UMI-77 exhibited robust anti-tumor efficacy with no toxicity. Also, UMI-77 decreased the anti-apoptotic protein survivin, which potently inhibited apoptosis by antagonizing caspase activity [1].
Reference:
[1]. Abulwerdi F, Liao C, Liu M, Azmi AS, et al. A novel small-molecule inhibitor of mcl-1 blocks pancreatic cancer growth in vitro and in vivo. Mol Cancer Ther, 2014, 13(3): 565-575.
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UMI-77 primes glioma cells for TRAIL-induced apoptosis by unsequestering Bim and Bak from Mcl-1.[Pubmed:28337703]
Mol Cell Biochem. 2017 Aug;432(1-2):55-65.
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.
