There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.
Type
HazMat fee for 500 gram (Estimated)
Excepted Quantity
USD 0.00
Limited Quantity
USD 15-60
Inaccessible (Haz class 6.1), Domestic
USD 80+
Inaccessible (Haz class 6.1), International
USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic
USD 100+
Accessible (Haz class 3, 4, 5 or 8), International
The mitochondrial pyruvate carriers (MPC) mediate pyruvate import into the mitochondria, which is key to the sustenance of the tricarboxylic cycle and oxidative phosphorylation[3]. In two distinct CRC mouse models, loss of Mpc1 prior to a tumorigenic stimulus doubled the frequency of adenoma formation and produced higher grade tumors. MPC loss was associated with a glycolytic metabolic phenotype and increased expression of stem cell markers. UK-5099 (PF-1005023) is a potent inhibitor of MPC[4]. UK-5099 (PF-1005023) inhibits pyruvate-dependent O2 consumption with an IC50 of 50 nM.[5]. The trypanosomal pyruvate carrier is found to be rather insensitive to inhibition by alpha-cyano-4-hydroxycinnamate (Ki=17 mM) but can be completely blocked by UK-5099 (Ki=49 mM)[6]. UK-5099 also inhibits the monocarboxylate transporter (MCT)[7]. UK5099 significantly inhibits the glucose-stimulated rise in oxygen consumption in a dose-dependent manner and at 150 μM reduced oxygen consumption below basal levels. UK5099 reduces ATP levels and increases ADP and AMP levels in 832/13 cells[8]. The UK5099 treated cells show significantly higher proportion of side population fraction and express higher levels of stemness markers Oct3/4 and Nanog. UK5099 application may be an ideal model for Warburg effect studies[9].
UK-5099 细胞实验
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.
Nat Cell Biol. 2017 Sep;19(9):1027-1036.
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.
Commun Biol. 2024 Jul 10;7(1):843.
4T1 cells
10 µM
24 hours
Exposure to UK-5099 induced a decrease in extracellular pH and oxygen consumption rate (OCR)
Free Radic Biol Med. 2024 Mar;213:11-18.
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.
J Med Chem. 2021 Feb 25;64(4):2046-2063.
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
Angew Chem Int Ed Engl. 2020 Mar 2;59(10):3896-3899.
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.
Neoplasia. 2023 Dec;46:100949.
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.
Proc Natl Acad Sci U S A. 2018 Apr 17;115(16):4152-4157.
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.
Cell Death Dis. 2024 Jun 19;15(6):431.
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.
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.
Cancer Metab. 2024 Oct 3;12(1):28.
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.
Mol Metab. 2024 Oct;88:102005.
Raji cells
50 µM
72 hours
Blockade of pyruvate mitochondrial transport, enhancing the efficacy of AZD3965, leading to increased cell death
Cancer Res. 2017 Nov 1;77(21):5913-5924.
Hut78 cells
50 µM
72 hours
Blockade of pyruvate mitochondrial transport, enhancing the anti-proliferative effects of AZD3965, increasing cell death
Cancer Res. 2017 Nov 1;77(21):5913-5924.
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.
Neoplasia. 2023 Dec;46:100949.
Human colon crypts
10 µM
UK-5099 treatment promoted human colon organoid colony formation and growth.
Nat Cell Biol. 2017 Sep;19(9):1027-1036.
UK-5099 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
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.
Commun Biol. 2024 Jul 10;7(1):843.
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
EBioMedicine. 2017 May;19:31-38
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.
J Med Chem. 2021 Feb 25;64(4):2046-2063.
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.
Nat Cell Biol. 2017 Sep;19(9):1017-1026
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
Free Radic Biol Med. 2024 Mar;213:11-18.
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.
Cell Death Dis. 2024 Jun 19;15(6):431.
BALB/c JNRj mice
4T1 breast cancer model
Intraperitoneal injection
3 mg/kg
Daily for four days
To evaluate the impact of MPC inhibitor UK-5099 on tumor extracellular pH, results showed a significant decrease in tumor pHe of 0.22 units
搜索
HazMat Fee +
