UMI-77

카탈로그 번호S7531 배치:S753103

인쇄

기술 자료

화학식

C18H14BrNO5S2
분자량 468.34 CAS 번호 518303-20-3
용해도 (25°C)* 시험관 내(In vitro) DMSO 93 mg/mL (198.57 mM)
Ethanol 93 mg/mL (198.57 mM)
Water Insoluble
생체 내(In Vivo) (개별적으로 순서대로 용매를 제품에 첨가하십시오.)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml은 약간 용해되거나 불용해됨을 의미합니다.
* Selleck은 모든 화합물의 용해도를 자체적으로 테스트하며, 실제 용해도는 게시된 값과 약간 다를 수 있습니다. 이는 정상적인 현상이며, 약간의 배치 간 변동으로 인해 발생합니다.
* 실온 배송 (안정성 테스트 결과 이 제품은 냉각 조치 없이 배송될 수 있음을 보여줍니다.)

원액 준비

생물학적 활성

설명 UMI-77 is a selective Mcl-1 inhibitor with Ki of 490 nM, showing selectivity over other members of Bcl-2 family.
표적
Mcl-1
(Cell-free assay)
490 nM(Ki)
시험관 내(In vitro) UMI-77 effectively disrupts the interactions between BL-Noxa and cellular Mcl-1, as well as Mcl-1/Bax protein–protein interactions. This compound inhibits growth of pancreatic cancer cells with IC50 of 3.4, 4.4, 12.5, 16.1, and 5.5 μM for BxPC-3, Panc-1, MiaPaCa-2, AsPC-1 and Capan-2 cells, respectively. It induced apoptosis in pancreatic cancer through activation of the intrinsic apoptotic pathway and/or Bax conformational change.
생체 내(In Vivo) In a BxPC-3 xenograft mouse model, UMI-77 (60 mg/kg i.v.) exhibits single-agent antitumor activity without any damage normal tissues.

프로토콜 (참조)

키나아제 분석:

[1]
  • Fluorescence polarization (FP)-based binding assays

    Based on the Kd values, the concentrations of the proteins used in the competitive binding experiments are 90 nM for Mcl-1, 40 nM for Bcl-w, 50 nM for Bcl-xL, 60 nM for Bcl-2, and 4 nM for A1/Bfl-1. The fluorescent probes, Flu-BID and FAM-BID are fixed at 2 nM for all assays except for A1/Bfl-1 where FAMBID is used at 1 nM. 5 μL of this compound in DMSO and 120 μL of protein/probe complex in the assay buffer (100 mM potassium phosphate, pH 7.5; 100 μg/ml bovine gamma globulin; 0.02% sodium azide) are added to assay plates (Microfluor 2Black), incubated at room temperature for 3 h and the polarization values (mP) are measured at an excitation wavelength at 485 nm and an emission wavelength at 530 nm using the plate reader Synergy H1Hybrid. IC50 values are determined by nonlinear regression fitting of the competition curves.
세포 분석:

[1]
  • 세포주

    Human pancreatic cancer cell lines AsPC-1, BxPC-3, Panc-1, MiaPaCa and Capan-2

  • 농도

    ~100 μM

  • 배양 시간

    4 days

  • 방법

    Human pancreatic cancer cell lines AsPC-1, BxPC-3, and Capan-2 are cultured in RPMI-1640 medium, whereas Panc-1 and MiaPaCa are cultured in Dulbeccos' Modified Eagle's Medium (DMEM), all supplemented with 10% FBS. The cell growth inhibition after treatment with increasing concentrations of this compound is determined by WST-8 assay.
동물 연구:

[1]
  • 동물 모델

    ICR-SCID mice bearing BxPC-3 tumor xenograft

  • 용량

    ~60 mg/kg daily

  • 투여

    i.v.

참조

  • https://pubmed.ncbi.nlm.nih.gov/24019208/

고객 제품 검증

<p>U87 and A172 cells were treated with UMI-77 (8 μM) for 24h and further treated with TRAIL (30  ng/ml) for indicated period of time. Levels of apoptosis-associated proteins were analyzed by Western blot. GAPDH was used as a loading control.</p>

, , Mol Cell Biochem, 2017, 432(1-2):55-65

(a) SVEC cells stably expressing FLAG-tBID 2A GFP-BCL-xL, FLAG-tBID 2A GFP-BCL-2 or FLAG-tBID 2A GFP-MCL-1 were transiently transfected with NOXA. Cell viability was analysed 24 h post-transfection by SYTOX Green dye exclusion and live-cell imaging using an IncuCyte imager. Error bars represent the s.e.m. of three independent experiments. (b) SVEC cells stably expressing FLAG-tBID 2A GFP-MCL-1 (MCL-1-dependent line) were treated with increasing concentrations of putative MCL-1 inhibitors UMI-77 or A-1210477. Cell viability was analysed 24 h post-treatment by SYTOX Green dye exclusion and live-cell imaging using an IncuCyte imager. Error bars represent the s.e.m. of three independent experiments. (c) MCL-1-dependent line was treated with UMI-77 or A-1210477 (both 10 μmol l−1) and analysed over time for cell viability by SYTOX Green dye exclusion and live-cell imaging using an IncuCyte imager. Error bars represent the s.e.m. of three independent experiments. (d,e) SVEC cells stably expressing FLAG-tBID 2A GFP-BCL-xL, FLAG-tBID 2A GFP-BCL-2 or FLAG-tBID 2A GFP-MCL-1 were treated with UMI-77 or A-1210477 (10 μM for 24 h) then cell viability was analysed by SYTOX Green dye exclusion and live-cell imaging using an IncuCyte imager (d) or by clonogenic survival assay (e). Error bars represent the s.e.m. of three independent experiments for d and s.d. of triplicate samples from a representative experiment carried out twice independently for e. In all cases, cells were treated with MCL-1 inhibitors in 3% FBS containing DMEM.

데이터 출처 [ , , Nat Commun, 2016, 7:10538 ]

MCL-1 pharmacological inhibitor UMI-77 induces apoptosis of ESCC cells. a, b KYSE150 (a) and KYSE510 (b) cells were starved in 0.1% FBS/RPMI 1640 medium overnight and then cultured without (DMSO) or with different concentrations of UMI-77 in 10% FBS/RPMI 1640 medium for 48 h. After treatment, attached and floating cells were harvested. Cleavage of caspase-3 and PARP were analyzed by Western blotting. β-actin was used as a loading control. c KYSE150 and KYSE510 cells were starved in 0.1% FBS/RPMI 1640 medium overnight and then cultured without (DMSO) or with 10 μM UMI-77 in 10% FBS/RPMI 1640 medium for 48 h. After treatment, attached and floating cells were harvested. Cleavage of PARP was analyzed by Western blotting. β-actin was used as a loading control. Arrow head: 17KD or 19 KD of cleaved caspase-3

데이터 출처 [ , , BMC Cancer, 2017, 17(1):449 ]

Selleck's UMI-77 인용됨 21 출판물

Therapy-induced normal tissue damage promotes breast cancer metastasis [ iScience, 2024, 27(1):108503] PubMed: 38161426
Deregulation and epigenetic modification of BCL2-family genes cause resistance to venetoclax in hematologic malignancies [ Blood, 2022, blood.2021014304] PubMed: 35704690
Proteogenomics refines the molecular classification of chronic lymphocytic leukemia [ Nat Commun, 2022, 13(1):6226] PubMed: 36266272
AXL/MERTK inhibitor ONO-7475 potently synergizes with venetoclax and overcomes venetoclax resistance to kill FLT3-ITD acute myeloid leukemia [ Haematologica, 2021, 10.3324/haematol.2021.278369] PubMed: 34732043
Development of potent and selective inhibitors targeting the papain-like protease of SARS-CoV-2 [ Cell Chem Biol, 2021, S2451-9456(21)00213-0] PubMed: 33979649
Mesothelioma Cells Depend on the Antiapoptotic Protein Bcl-xL for Survival and Are Sensitized to Ionizing Radiation by BH3-Mimetics. [ Int J Radiat Oncol Biol Phys, 2020, 15;106(4):867-877] PubMed: 31786278
Targeting the Synthetic Vulnerability of PTEN-Deficient Glioblastoma Cells with MCL1 Inhibitors [ Mol Cancer Ther, 2020, 19(10):2001-2011] PubMed: 32737157
AT101 [(-)-Gossypol] Selectively Inhibits MCL1 and Sensitizes Carcinoma to BH3 Mimetics by Inducing and Stabilizing NOXA [ Cancers (Basel), 2020, 12(8):E2298] PubMed: 32824203
Alveolar Macrophage Apoptosis-associated Bacterial Killing Helps Prevent Murine Pneumonia. [ Am J Respir Crit Care Med, 2019, 200(1):84-97] PubMed: 30649895
Confounding off-target effects of BH3 mimetics at commonly used concentrations: MIM1, UMI-77, and A-1210477 [ Cell Death Dis, 2019, 10(3):185] PubMed: 30796196

반품 정책
Selleck Chemical의 무조건 반품 정책은 고객에게 원활한 온라인 쇼핑 경험을 보장합니다. 구매에 어떤 식으로든 불만족하시면, 수령일로부터 7일 이내에 모든 품목을 반품하실 수 있습니다. 제품 품질 문제(프로토콜 관련 문제 또는 제품 관련 문제)가 발생하는 경우, 원래 구매일로부터 365일 이내에 모든 품목을 반품하실 수 있습니다. 제품 반품 시 아래 지침을 따르십시오.

배송 및 보관
Selleck 제품은 실온에서 운송됩니다. 실온에서 제품을 받으셨더라도 안심하십시오. Selleck 품질 검사 부서에서 한 달간의 상온 보관이 분말 제품의 생물학적 활성에 영향을 미치지 않음을 확인하는 실험을 수행했습니다. 수령 후, 데이터시트에 설명된 요구 사항에 따라 제품을 보관하십시오. 대부분의 Selleck 제품은 권장 조건에서 안정적입니다.

인간, 수의학 진단 또는 치료 용도로 사용하지 마십시오.