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Chemical Structure| 56396-35-1 Chemical Structure| 56396-35-1

Structure of UK-5099
CAS No.: 56396-35-1

Chemical Structure| 56396-35-1

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UK-5099 is a potent is MPC (mitochondrial pyruvate carrier) inhibitor with IC50 value of 50 nM.

Synonyms: PF-1005023

4.5 *For Research Use Only !

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Product Details of UK-5099

CAS No. :56396-35-1
Formula : C18H12N2O2
M.W : 288.30
SMILES Code : O=C(O)/C(C#N)=C/C1=CN(C2=CC=CC=C2)C3=C1C=CC=C3
Synonyms :
PF-1005023
MDL No. :MFCD19443867
InChI Key :BIZNHCWFGNKBBZ-JLHYYAGUSA-N
Pubchem ID :6438504

Safety of UK-5099

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302+H312-H315-H318-H411
Precautionary Statements:P264-P270-P273-P280-P301+P312+P330-P302+P352+P312-P305+P351+P338+P310-P332+P313-P391-P501
Class:9
UN#:3077
Packing Group:

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Lgr5-EGFP+ cells 10 µM 16 hours UK-5099 treatment significantly increased the percentage of GFP positive cells, indicating that MPC inhibition enhances stem cell function. PMC6137334
T315I-Bcr-Abl-32D cells 25 μM 16 hours UK-5099 treatment reduced GSH levels in T315I-Bcr-Abl cells and induced replication stress, making these cells more sensitive to JMF4073. PMC11237035
4T1 cells 10 μM 24 hours Exposure to UK-5099 induced a decrease in extracellular pH and oxygen consumption rate (OCR) PMC10923140
MCF10A cells 10 μM 24-30 hours To evaluate the ability of analogues to promote cellular lactate production, results showed that several analogues significantly increased lactate production rate. PMC8939290
human T cells 10 μM 3 hours To assess the cellular target engagement selectivity of UK-5099 for MPC2, showing sub-μM IC50 values for selective MPC2 engagement PMC7323913
MDA-MB-231 cells 10 μM 30 minutes To assess the importance of mitochondrial pyruvate metabolism in MDA-MB-231 cells, results showed that UK-5099 significantly reduced mitochondrial respiration in persistent cells. PMC10661600
HCT116 cells 3 mM 40 minutes UK5099 treatment blocked the generation of all observed metabolites as well as the consumption of pyruvate, indicating that these metabolites were produced by mitochondrial enzymes in intact mitochondria. PMC5910857
H661 20 μM 48 hours The combination of UK-5099 and Syrosingopine significantly inhibited the proliferation of NSCLC cells and induced cell cycle arrest and apoptosis. PMC11187063
PC-9 20 μM 48 hours The combination of UK-5099 and Syrosingopine significantly inhibited the proliferation of NSCLC cells and induced cell cycle arrest and apoptosis. PMC11187063
PDAC PDOs (pancreatic ductal adenocarcinoma patient-derived organoids) 5 µM 48 hours To investigate the effect of UK-5099 on the metabolic activity of PDAC PDOs. Results showed that UK-5099 treatment increased glycolytic activity in basal-like tumor PDOs and reduced maximal respiration, indicating that basal-like tumor PDOs are more sensitive to MPC1 inhibition. PMC11448267
3T3L1 adipocytes 5 μM 6 hours Treatment with UK5099 led to a ~50% reduction in pyruvate incorporation into the total lipid pool, indicating that UK5099 inhibits the function of the mitochondrial pyruvate carrier (MPC), thereby affecting lipid synthesis in adipocytes. PMC11382204
Raji cells 50 µM 72 hours Blockade of pyruvate mitochondrial transport, enhancing the efficacy of AZD3965, leading to increased cell death PMC5669455
Hut78 cells 50 µM 72 hours Blockade of pyruvate mitochondrial transport, enhancing the anti-proliferative effects of AZD3965, increasing cell death PMC5669455
MDA-MB-231 cells 10 μM 96 hours To evaluate the effect of UK-5099 combined with chemotherapeutic drugs on cell growth, results showed that UK-5099 synergistically inhibited the growth of persistent cells with chemotherapeutic drugs. PMC10661600
Human colon crypts 10 µM UK-5099 treatment promoted human colon organoid colony formation and growth. PMC6137334

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
C57BL/6J animals C57BL/6J mice Topical administration 20μM 48 hours Topical treatment with UK-5099 accelerated the activation of hair follicle stem cells (HFSCs) and the hair cycle, and increased lactate levels in HFSCs. PMC5657543
Mice patient-derived xenograft tumor model Oral 10 mg/kg twice daily or 100 mg/kg/day daily daily treatment for 3 weeks UK-5099 slowed the growth of patient-derived xenograft (PDX) tumors in mice without severe loss of animal body weight PMC5440602
BALB/cAnNRj mice 4T1 breast cancer model intraperitoneal injection 3 mg/kg once daily for 4 days UK-5099 treatment induced a significant decrease in tumor pH, but no significant change in tumor oxygenation was observed PMC10923140
Balb/c Nude mice Subcutaneous tumor model Intraperitoneal injection 3 mg/kg Continuously for 14 days The combination of UK-5099 and Syrosingopine significantly inhibited the growth of subcutaneous tumors without significant toxic side effects. PMC11187063
C57BL/6J mice Hair loss model Topical administration 20 μM Every other day for 3 weeks To evaluate the ability of analogues to promote hair growth in mice, results showed that several analogues significantly accelerated hair growth. PMC8939290
C3H/HeNCrNarl mice T315I-Bcr-Abl-32D cell-induced leukemia model Intraperitoneal injection 10 mg/kg Every 24 hours for 14 days UK-5099 monotherapy did not significantly affect the survival of T315I leukemia mice, but combination therapy with JMF4073 significantly prolonged survival and reduced the burden of leukemia cells. PMC11237035

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

3.47mL

0.69mL

0.35mL

17.34mL

3.47mL

1.73mL

34.69mL

6.94mL

3.47mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

[1]Zhong Y, Li X, et al. Application of mitochondrial pyruvate carrier blocker UK5099 creates metabolic reprogram and greater stem-like properties in LnCap prostate cancer cells in vitro. Oncotarget. 2015 Nov 10;6(35):37758-69.

[2]Hinoi E, Takarada T, et al. A molecular mechanism of pyruvate protection against cytotoxicity of reactive oxygen species in osteoblasts. Mol Pharmacol. 2006 Sep;70(3):925-35.

[3]Bor Luen Tang. Targeting the Mitochondrial Pyruvate Carrier for Neuroprotection. Brain Sci. 2019 Sep 18;9(9):238.

[4]Claire L Bensard ,et al. Regulation of Tumor Initiation by the Mitochondrial Pyruvate Carrier. Cell Metab. 2020 Feb 4;31(2):284-300.e7.

[5] Halestrap AP. The mitochondrial pyruvate carrier. Kinetics and specificity for substrates and inhibitors. Biochem J. 1975 April; 148(1): 85-96.

[6] Wiemer EA, et al. The inhibition of pyruvate transport across the plasma membrane of the bloodstream form of Trypanosoma brucei and its metabolic implications. Biochem J. 1995 Dec 1;312 ( Pt 2):479-84.

[7]Hinoi E, et al. A molecular mechanism of pyruvate protection against cytotoxicity of reactive oxygen species in osteoblasts. Mol Pharmacol. 2006 Sep;70(3):925-35. Epub 2006 Jun 9.

[8]Patterson JN, et al. Mitochondrial metabolism of pyruvate is essential for regulating glucose-stimulated secretion. J Biol Chem. 2014 May 9;289(19):13335-46.

[9]Zhong Y, et al. Application of mitochondrial pyruvate carrier blocker UK5099 creates metabolic reprogram and greater stem-like properties in LnCap prostate cancer cells in vitro. Oncotarget. 2015 Nov 10;6(35):37758-69.

 

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