UMI-77
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MedKoo CAT#: 407303

CAS#: 518303-20-3

Description: UMI-77 is selective Mcl-1 SMI inhibitor. UMI-77 blocks pancreatic cancer growth in vitro and in vivo. MI-77 binds to the BH3-binding groove of Mcl-1 with Ki of 490 nmol/L, showing selectivity over other members of the antiapoptotic Bcl-2 family. UMI-77 inhibits cell growth and induces apoptosis in pancreatic cancer cells in a time- and dose-dependent manner, accompanied by cytochrome c release and caspase-3 activation. In an in vivo BxPC-3 xenograft model, UMI-77 effectively inhibited tumor growth. Western blot analysis in tumor remnants revealed enhancement of proapoptotic markers and significant decrease of survivin.


Chemical Structure

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UMI-77
CAS# 518303-20-3

Theoretical Analysis

MedKoo Cat#: 407303
Name: UMI-77
CAS#: 518303-20-3
Chemical Formula: C18H14BrNO5S2
Exact Mass: 466.9497
Molecular Weight: 468.336
Elemental Analysis: C, 46.16; H, 3.01; Br, 17.06; N, 2.99; O, 17.08; S, 13.69

Price and Availability

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10.0mg USD 150.0 Ready to ship
25.0mg USD 250.0 Ready to ship
50.0mg USD 450.0 Ready to ship
100.0mg USD 650.0 Ready to ship
200.0mg USD 950.0 Ready to ship
500.0mg USD 2150.0 2 weeks
1.0g USD 2750.0 2 weeks
2.0g USD 3950.0 2 weeks
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Synonym: UMI-77, UMI77, UMI 77

IUPAC/Chemical Name: 2-((4-((4-bromophenyl)sulfonamido)-1-hydroxynaphthalen-2-yl)thio)acetic acid

InChi Key: WUGANDSUVKXMEC-UHFFFAOYSA-N

InChi Code: 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)

SMILES Code: C1=CC=C2C(=C1)C(=CC(=C2O)SCC(=O)O)NS(=O)(=O)C3=CC=C(C=C3)Br

Appearance: White to off-white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: 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 activity: Since attenuation of MCL-1 by RNA interference lowered the threshold at which KYSE150 and KYSE510 cells undergo apoptosis and led to sensitization of these cells to undergo apoptosis triggered by cisplatin (Figs. 55 and 66), a small molecule inhibitor of MCL-1 might also enhance the sensitivity of ESCC cells to this chemotherapy drug. UMI-77, a recently characterized MCL-1-specific inhibitor, was used to investigate the possibility. KYSE150 and KYSE510 cells were treated with UMI-77 for 48 h. Apoptosis was up-regulated in a dose dependent manner, as indicated by the presence of cleaved caspase-3 and cleaved PARP in these cell lines (Fig. 7a and b). As expected, KYSE150 cells with higher BCL-xL level showed less sensitive to UMI-77 and less susceptible to apoptosis than did KYSE510 cells (Fig. 1a and b , Fig. 7c ). Co-immunoprecipitation data indicated that treatment of UMI-77 resulted in disruption of the endogenous MCL-1/BAX (Fig. 8a and c) and MCL-1/BAK (Fig. 8b and d) interactions in both KYSE150 and KYSE510 cells, which were in line with a previous report. Reference: BMC Cancer. 2017; 17: 449. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490225/
In vivo activity: Daily treatment with UMI-77 for 5 consecutive days a week for two weeks resulted 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 (Fig. 5C). To elucidate the molecular mechanism of UMI-77 mediated tumor growth inhibition, western blot and immunohistochemistry on tumor tissue were performed. The western blots of the tumor tissue lysates showed slightly elevated levels of pro-apoptotic proteins, Bax and Bak, and significant decrease of survivin, one of the Inhibitors of Apoptosis Proteins (IAPs) which potently inhibits apoptosis by antagonizing caspase activity (Fig. 5D). The apoptotic cells in tumor tissue were determined by TUNEL-based in situ method and the obtained results showed that positive apoptotic cells of tumor sections were significantly increased in UMI-77-treated BxPC-3 xenograft mice as compared with the control group (Fig. 5E). The toxicity of UMI-77 on normal tissues was examined by H&E analyses (Fig. S9). Histopathology revealed that treatment of mice with UMI-77 did not cause damage to tested tissues from kidney, liver and pancreas, demonstrating that it is not toxic to normal mouse tissues. These findings provide in vivo support of the involvement of Mcl-1 regulated pathway in PC, implicating the potential of Mcl-1 inhibitors as novel antitumor agents for treatment of PC. Reference: Mol Cancer Ther. 2014 Mar; 13(3): 565–575. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4174574/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 14.25 30.43
DMF 2.0 4.27
Ethanol 5.0 10.68
Ethanol:PBS (pH 7.2) (1:8) 0.11 0.23

Preparing Stock Solutions

The following data is based on the product molecular weight 468.336 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Robinson EJ, Aguiar SP, Kouwenhoven WM, Starmans DS, von Oerthel L, Smidt MP, van der Heide LP. Survival of midbrain dopamine neurons depends on the Bcl2 factor Mcl1. Cell Death Discov. 2018 Nov 21;4:107. doi: 10.1038/s41420-018-0125-7. PMID: 30479840; PMCID: PMC6249233. 2. Yu X, Li W, Xia Z, Xie L, Ma X, Liang Q, Liu L, Wang J, Zhou X, Yang Y, Liu H. Targeting MCL-1 sensitizes human esophageal squamous cell carcinoma cells to cisplatin-induced apoptosis. BMC Cancer. 2017 Jun 28;17(1):449. doi: 10.1186/s12885-017-3442-y. PMID: 28659182; PMCID: PMC5490225. 3. Cen X, Xu X, Xia H. Targeting MCL1 to induce mitophagy is a potential therapeutic strategy for Alzheimer disease. Autophagy. 2021 Mar;17(3):818-819. doi: 10.1080/15548627.2020.1860542. Epub 2020 Dec 20. PMID: 33342330; PMCID: PMC8032245. 4. Abulwerdi F, Liao C, Liu M, Azmi AS, Aboukameel A, Mady AS, Gulappa T, Cierpicki T, Owens S, Zhang T, Sun D, Stuckey JA, Mohammad RM, Nikolovska-Coleska Z. 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. doi: 10.1158/1535-7163.MCT-12-0767. Epub 2013 Sep 9. PMID: 24019208; PMCID: PMC4174574.
In vitro protocol: 1. Robinson EJ, Aguiar SP, Kouwenhoven WM, Starmans DS, von Oerthel L, Smidt MP, van der Heide LP. Survival of midbrain dopamine neurons depends on the Bcl2 factor Mcl1. Cell Death Discov. 2018 Nov 21;4:107. doi: 10.1038/s41420-018-0125-7. PMID: 30479840; PMCID: PMC6249233. 2. Yu X, Li W, Xia Z, Xie L, Ma X, Liang Q, Liu L, Wang J, Zhou X, Yang Y, Liu H. Targeting MCL-1 sensitizes human esophageal squamous cell carcinoma cells to cisplatin-induced apoptosis. BMC Cancer. 2017 Jun 28;17(1):449. doi: 10.1186/s12885-017-3442-y. PMID: 28659182; PMCID: PMC5490225.
In vivo protocol: 1. Cen X, Xu X, Xia H. Targeting MCL1 to induce mitophagy is a potential therapeutic strategy for Alzheimer disease. Autophagy. 2021 Mar;17(3):818-819. doi: 10.1080/15548627.2020.1860542. Epub 2020 Dec 20. PMID: 33342330; PMCID: PMC8032245. 2. Abulwerdi F, Liao C, Liu M, Azmi AS, Aboukameel A, Mady AS, Gulappa T, Cierpicki T, Owens S, Zhang T, Sun D, Stuckey JA, Mohammad RM, Nikolovska-Coleska Z. 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. doi: 10.1158/1535-7163.MCT-12-0767. Epub 2013 Sep 9. PMID: 24019208; PMCID: PMC4174574.

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1: Dunford EC, Herbst EA, Jeoung NH, Gittings W, Inglis JG, Vandenboom R, LeBlanc PJ, Harris RA, Peters SJ. PDH activation during in vitro muscle contractions in PDH kinase 2 knockout mice: effect of PDH kinase 1 compensation. Am J Physiol Regul Integr Comp Physiol. 2011 Jun;300(6):R1487-93. doi: 10.1152/ajpregu.00498.2010. Epub 2011 Mar 16. PubMed PMID: 21411764.

2: Goldstein DM, Soth M, Gabriel T, Dewdney N, Kuglstatter A, Arzeno H, Chen J, Bingenheimer W, Dalrymple SA, Dunn J, Farrell R, Frauchiger S, La Fargue J, Ghate M, Graves B, Hill RJ, Li F, Litman R, Loe B, McIntosh J, McWeeney D, Papp E, Park J, Reese HF, Roberts RT, Rotstein D, San Pablo B, Sarma K, Stahl M, Sung ML, Suttman RT, Sjogren EB, Tan Y, Trejo A, Welch M, Weller P, Wong BR, Zecic H. Discovery of 6-(2,4-difluorophenoxy)-2-[3-hydroxy-1-(2-hydroxyethyl)propylamino]-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (pamapimod) and 6-(2,4-difluorophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (R1487) as orally bioavailable and highly selective inhibitors of p38α mitogen-activated protein kinase. J Med Chem. 2011 Apr 14;54(7):2255-65. doi: 10.1021/jm101423y. Epub 2011 Mar 4. PubMed PMID: 21375264.

UMI-77

10.0mg / USD 150.0