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Table 1 Drugs targeting metabolic activities in myeloid leukemia

From: Exploiting metabolic vulnerabilities for personalized therapy in acute myeloid leukemia

Target protein or process Pathway impacted Drug Patient group Preclinical studies Clinical trials
Hexokinases Glycolysis 2-Deoxyglucose AML [10] -
AML with FTL3-ITD mutation [23,24,25] -
mTOR kinase mTOR-dependent metabolic pathways Sirolimus (rapamycin), temsirolimus, everolimus AML/ CML [19,20,21,22] Phase I/II
Glutaminase Glutaminolysis CB839 AML [26, 27] Phase I
AML with IDH mutations [28] -
Asparagine glutamine availability Amino acid metabolism Erwinase alone L-asparaginase (encapsulated in red blood cells) + low-dose cytarabine AML   Phase I/II
Arginine availability Nucleotides polyamines biosynthesis ADI-PEG20 AML [29] Phase I/II [30]
CKMT1 Creatine biosynthesis and OxPHOS Cyclocreatine AML with EVI1 aberrant expression [31] -
Mitochondrial protein translation OxPHOS Tigecycline AML [32] Phase I
Mitochondrial protease ClpP OxPHOS A2-32-01 AML [33] -
mtDNA polymerase OxPHOS 2'3'-Dideoxycytidine AML [34] -
ETC complex I OxPHOS Metformin AML [35, 36] Phase I
IACS-010759 AML [37] Phase I
DHODH Nucleotides and OxPHOS Brequinar sodium BRQ AML [38] Phase I/II
HZ00 CML [39] -
Isobavalchone AML [40] -
PTC299 AML [41] Phase Ib
CPT1a Fatty acid oxidation Etomoxir AML [42, 43] -
Avocatin B [44, 45] -
ST1326 [46] -
Mitochondrial anti-apoptotic BCL2 OxPHOS and pyrimidine biosynthesis Venetoclax ABT-199 AML/ CML [47,48,49] Phase I/II/III [50]
AML with FTL3-ITD mutation [51] Phase I/II in combination with FLT3-ITD inhibitor
AML with IDH1 mutation [52] Phase I/II in combination with IDH1 mutant inhibitor
Amino acid transporters AA metabolism and OxPHOS Venetoclax ABT-199 + azacitidine AML [48] Phase I/II/III [50]
IDH2 mutant enzyme 2-HG production Enasidenib AG-221 AML with IDH2 mutation [53,54,55] FDA approved phase I/III
IDH1 mutant enzyme 2-HG production Ivosidenib AG-120 AML with IDH1 mutation [56, 57] FDA approved phase I/III
BAY1436032 [58,59,60] Phase I
IDH305   Phase I [61]
IDH1/IDH2 mutant enzyme 2-HG production Vorasidenib AG-881 AML with IDH1 and/or IDH2 mutation   Phase I [62]
HMG-CoA reductase Mevalonate biosynthesis Statins: lovastatin, pravastatin AML [63,64,65] Phase I/II [66, 67]
Stearoyl CoA desaturase 1 Lipid biosynthesis BaP = combination of lipid-regulating bezafibrate and the sex hormone medroxyprogesterone acetate AML [68,69,70] -