Lactate Dehydrogenase Inhibitor

Oxamic acid (oxamate) sodium salt is a lactate dehydrogenase-A (LDH-A) inhibitor. Oxamic acid sodium salt shows anti-tumor activity, and anti-proliferative activity against cancer cells, and can induce apoptosis.

GSK2837808A is a potent and selective lactate dehydrogenase A (LDHA) inhibitor with IC₅₀s of 2.6 and 43 nM for hLDHA and hLDHB, respectively.

FX-11 is a potent, selective, reversible and competitive lactate dehydrogenase A (LDHA) inhibitor, with a K_i of 8 μM. FX-11 reduces ATP levels and induces oxidative stress, ROS production and cell death. FX-11 shows antitumor activity in lymphoma and pancreatic cancer xenografts.

(R)-GNE-140 is a potent inhibitor of lactate dehydrogenase (LDH) A, B and C, with IC₅₀ values of 3, 5 and 5 nM against LDHA, LDHB, LDHC, respectively. (R)-GNE-140 blocks the conversion of pyruvate to lactate, reduces lactate production and histone lysine lactylation, and inhibits glycolysis. (R)-GNE-140 attenuates cardiac hypertrophy, alleviates PM_2.5-induced pulmonary inflammation and fibrosis, blocks MRSA-induced Arg1 expression. (R)-GNE-140 is applicable to research related to pathological cardiac hypertrophy, pulmonary fibrosis, MRSA infection and pancreatic cancer.

Ravoxertinib (GDC-0994) is an orally active ERK1/2 inhibitor. Ravoxertinib inhibits the ERK1/2 MAPK signaling pathway and reduces the expression levels of c-Myc, HK2 and LDHA. Ravoxertinib decreases mammosphere formation, and exerts additive and/or superadditive cytotoxicity when combined with Ipatasertib (HY-15186) in 3D tumor sphere models. Ravoxertinib can be used in research related to various cancers including breast cancer, melanoma, head and neck cancer, non-small cell lung cancer, ovarian cancer and Merkel cell carcinoma.

Oxamic acid is a lactate dehydrogenase-A (LDH-A) inhibitor. Oxamic acid shows anti-tumor activity, and anti-proliferative activity against cancer cells, and can induce apoptosis.

Galloflavin is a potent lactate dehydrogenase (LDH) inhibitor. The calculated K_is for pyruvate are 5.46 μM (LDH-A) and 15.06 μM (LDH-B). Galloflavin hinders the proliferation of cancer cells by blocking glycolysis and ATP production.

AXKO-0046, indole derivative, is an uncompetitive Lactate dehydrogenase B (LDHB) selective inhibitor.AXKO-0046 has LDHB inhibitory activity with an EC₅₀ value of 42 nM.AXKO-0046 can be used for the research of cancer metabolism.

Lathosterol is a plant sterol and cholesterol-like molecule. Lathosterol increases antioxidant enzymes (such as SOD, CAT, and GSH) and decreases LDH. Lathosterol has a hepatoprotective effect on mice with acetaminophen (HY-66005)-induced liver injury^[1].

AGN 192403 (BRD4780) hydrochloride is a potent and selective imidazoline-1 receptor antagonist with a K_i value of 42 nM. AGN 192403 hydrochloride is also a TMED9 inhibitor. AGN 192403 hydrochloride shows protective effects on oxidative cytotoxicity and mitochondrial inhibitor-induced cytotoxicity in astrocytes. AGN 192403 hydrochloride mitigates the proliferation and migration of differentiated glioma tumor cells. AGN 192403 hydrochloride can be used for glioma tumor and neurological diseases research.

GNE-140 racemate is a racemic mixture of (R)-GNE-140 (HY-100742A) and (S)-GNE-140 (HY-100742B), and also a tautomer of GNE-140 (HY-118241). GNE-140 racemate is an orally active lactate dehydrogenase inhibitor, with an IC₅₀ of 3 nM against human LDHA and an IC₅₀ of 5 nM against LDHB. GNE-140 racemate reduces the phosphorylation level and total protein expression of p38 MAPK, and inhibits EGF-induced AKT phosphorylation. GNE-140 racemate decreases lactate production, regulates glycolysis, the pentose phosphate pathway and nucleotide biosynthesis, increases extracellular pH, inhibits cell proliferation, migration and invasion, and induces caspase-3 activation and ROS accumulation. GNE-140 racemate can be used in research related to breast cancer, cystic fibrosis and pancreatic cancer.

Linalyl acetate is the principal components of many plant essential oils. Linalyl acetate exhibits anti-anxiety, anti-inflammatory, anti-diabetic, anti-stress, and cardiovascular-regulatory effects. Linalyl acetate is orally active.

CAY10594 is an orally active PLD2 inhibitor with an IC₅₀ of 140 nM. CAY10594 has activities such as anti-tumor, anti-oxidation and liver protection. CAY10594 can be used for the research of diseases like breast cancer, acute liver injury and colitis.

Nedosiran (DCR-PHXC) sodium is an RNA interference (RNAi) targeting lactate dehydrogenase (LDH). Nedosiran sodium represents an impactful potential therapeutic for primary hyperoxaluria (PH) with end-stage renal disease (ESRD). Nedosiran sodium is a GalNAc-dsRNA conjugate.

LDHA-IN-3 (compound 2), as a selenobenzene compound, is a potent, noncompetitive lactate dehydrogenase (LDHA) inhibitor (IC₅₀=145.2 nM). LDHA-IN-3 can be used for the research of cancer.

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.

Sodium mercaptopyruvate serves as a substrate for Lactate dehydrogenase and Sulfurtransferase. Sodium mercaptopyruvate forms through enzymatic transamination and oxidative deamination of L-cysteine (HY-Y0337). Sodium mercaptopyruvate abolishes lactate dehydrogenase reaction activity. It increases urinary thiosulfate excretion, fails to sustain rat growth by replacing L-cystine (HY-N0394), and does not induce morbidity or mortality in mice. Sodium mercaptopyruvate is applicable to research related to 3-mercaptopyruvate disulfiduria and 3-mercaptolactate disulfiduria.

2-Oxovaleric acid is an analog of Pyruvate and a substrate inhibitor of Lactate dehydrogenase, exhibiting substrate inhibitory activity against lactate dehydrogenase from Phycomyces blakesleeanus.

AZ-33 (LDHA-IN-4) (compound 33) is a selective lactate dehydrogenase A (LDHA) inhibitor with an IC₅₀ of 0.5 μM and a K_d of 0.093 μM.

Ravoxertinib hydrochloride (GDC-0994 hydrochloride) is an orally active ERK1/2 inhibitor. Ravoxertinib hydrochloride inhibits the ERK1/2 MAPK signaling pathway and reduces the expression levels of c-Myc, HK2 and LDHA. Ravoxertinib hydrochloride decreases mammosphere formation, and exerts additive and/or superadditive cytotoxicity when combined with Ipatasertib (HY-15186) in 3D tumor sphere models. Ravoxertinib hydrochloride can be used in research related to various cancers including breast cancer, melanoma, head and neck cancer, non-small cell lung cancer, ovarian cancer and Merkel cell carcinoma.