LDH-IN-1 is a novel pyrazole-based inhibitor of human lactate dehydrogenase (LDH) with IC₅₀s of 32 and 27 nM for LDHA and LDHB, respectively.

IC50: 32 nM (LDHA), 27 nM (LDHB)^[1]

LDH-IN-1 exhibits low nM inhibition of both LDHA and LDHB (IC₅₀=32, 27 nM, respectively), submicromolar inhibition of lactate production, and inhibition of lactate in MiaPaCa2 pancreatic cancer and A673 sarcoma cells (IC₅₀=0.517, 0.854μM, respectively). LDH-IN-1 inhibits the growth of MiaPaCa2 pancreatic cancer and A673 sarcoma cells with IC₅₀s of 2.23 and 1.21 μM). Dose−response treatment of MiaPaCa-2 cells with LDH-IN-1 shows effects on cellular proliferation at concentrations as low as 250 nM and with nearly complete arrest of cell growth at 20 μM^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

LDH-IN-1 shows clearance values that far exceed hepatic blood flow (HBF) in mouse species (90 mL/min/kg), with in vivo clearances of 227 mL/min/kg^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

570.68

C₃₀H₂₆N₄O₄S₂

1964515-43-2

Room temperature in continental US; may vary elsewhere.

DMSO : 52 mg/mL (91.12 mM; Need ultrasonic)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.17 mg/mL (3.80 mM); Clear solution

  此方案可获得 ≥ 2.17 mg/mL (3.80 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 21.7 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.17 mg/mL (3.80 mM); Clear solution

  此方案可获得 ≥ 2.17 mg/mL (3.80 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 21.7 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Rai G, et al. Discovery and Optimization of Potent, Cell-Active Pyrazole-Based Inhibitors of Lactate Dehydrogenase (LDH). J Med Chem. 2017 Nov 22;60(22):9184-9204.

A673 and MiaPaCa-2 cellsA673 and MiaPaCa-2 cells are cultured and plated in 1536-well white solid tissue culture plates. A 1536-well pintool dispenser outfitted with 20 nL pins is used to transfer 23 nL of LDH-IN-1 in DMSO to the 1536-well assay plates. After a 48 h incubation at 37°C, 2.5 μL of CellTiter-Glo is dispensed into each well using a BioRAPTR FRD dispenser. Plates are incubated at room temperature for 10 min, transferred to a ViewLux microplate imager, and the ATP-coupled luminescence is measured using a 1 s exposure^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Mice^[1]

Male CD1 mice approximately 6−8 weeks of age and a weight of approximately 20−30 g, are dosed with LDH-IN-1 at 2 mg/ kg (iv) and 50 mg/kg (po). Each cohort had three mice, and plasma is collected at 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 8 h, 12 h, and 24h postdose for iv and 15 min 30 min, 1 h, 2 h, 4 h, 8 h, 12 h, and 24 h for po. Approximately 0.025 mL of blood is collected via the dorsal metatarsal vein at each time point. Blood samples are then transferred into plastic microcentrifuge tubes containing heparin−Na as anticoagulant. Samples are then centrifuged at 4000g for 5 min at 4 °C to obtain plasma. Plasma samples are then stored in polypropylene tubes, quickly frozen, and kept at −75 °C until analyzed by LC/MS/MS^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Rai G, et al. Discovery and Optimization of Potent, Cell-Active Pyrazole-Based Inhibitors of Lactate Dehydrogenase (LDH). J Med Chem. 2017 Nov 22;60(22):9184-9204.